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<body lang=3DFR-CA style=3D'tab-interval:35.4pt'>

<div class=3DSection1>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b style=3D'mso-bidi-font-weight:normal'><span
style=3D'font-size:14.0pt;font-family:"Times New Roman"'>La thrombop&eacute=
;nie
induite par l&#8217;h&eacute;parine<o:p></o:p></span></b></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"Ti=
mes New Roman"'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b style=3D'mso-bidi-font-weight:normal'><span
style=3D'font-size:14.0pt;font-family:"Times New Roman"'>Introduction<o:p><=
/o:p></span></b></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman"'>La
thrombop&eacute;nie induite par l&#8217;h&eacute;parine (TIH) est un syndro=
me
prothombotique grave d&#8217;origine immune caract&eacute;ris&eacute; par u=
ne
diminution significative des plaquettes suite &agrave; l&#8217;administrati=
on
d&#8217;une h&eacute;parine<sup>(1-,3)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span><st1:PersonName ProductID=3D"La TI=
H"
w:st=3D"on">La TIH</st1:PersonName> repr&eacute;sente la cause la plus impo=
rtante
et la plus fr&eacute;quente de thrombop&eacute;nie chez les patients
hospitalis&eacute;s<sup>(4,5)</sup>.<span style=3D'mso-spacerun:yes'>&nbsp;
</span>Environ 3 &agrave; 5 % des patients expos&eacute;s &agrave;
l&#8217;h&eacute;parine non fractionn&eacute;e (HNF) pr&eacute;sentent une
thrombop&eacute;nie induite par l&#8217;h&eacute;parine alors que ce syndro=
me
touche seulement 0,5% des patients expos&eacute;s aux h&eacute;parines de
faible poids mol&eacute;culaire (HFPM)<sup>(5)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span><st1:PersonName ProductID=3D"La TI=
H"
w:st=3D"on">La TIH</st1:PersonName> est un sujet d&#8217;int&eacute;r&ecirc=
;t
puisque, en plus d&#8217;&ecirc;tre associ&eacute;e</span><span lang=3DFR
style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-fareast-font-fa=
mily:
"Times New Roman";mso-ansi-language:FR;mso-fareast-language:FR'> &agrave; u=
ne
morbidit&eacute; et une mortalit&eacute; importante,</span><span lang=3DFR
style=3D'font-size:12.0pt;font-family:"Times New Roman"'> </span><span
style=3D'font-size:12.0pt;font-family:"Times New Roman"'>l</span><span lang=
=3DFR
style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-fareast-font-fa=
mily:
"Times New Roman";mso-ansi-language:FR;mso-fareast-language:FR'>es patients=
 qui
d&eacute;veloppent ce syndrome sont &agrave; risque de pr&eacute;senter des
complications s&eacute;v&egrave;res telles que des &eacute;v&eacute;nements
thrombotiques ou des n&eacute;croses cutan&eacute;es<sup>(2,5)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>En effet, environ 20 &agrave; 50% =
des
patients qui pr&eacute;sentent ce syndrome et qui ne sont pas trait&eacute;=
s,
manifestent, dans les 30 jours suivant le diagnostic de TIH, un &eacute;v&e=
acute;nement
thrombotique qui peut mener &agrave; l&#8217;amputation d&#8217;un membre v=
oire
au d&eacute;c&egrave;s des patients<sup>(2,3,6)</sup>.</span><span lang=3DFR
style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-bidi-font-weigh=
t:
bold'> </span><span style=3D'font-size:12.0pt;font-family:"Times New Roman";
mso-bidi-font-weight:bold'><o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"Ti=
mes New Roman"'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b><span style=3D'font-size:14.0pt;font-family:=
"Times New Roman"'>&Eacute;tiologie
/ Pathophysiologie / Diagnostic<o:p></o:p></span></b></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>D&#8217;abord, il existe 2 types de
thrombop&eacute;nie induite &agrave; l&#8217;h&eacute;parine soit <st1:Pers=
onName
ProductID=3D"La TIH" w:st=3D"on">la TIH</st1:PersonName> de type I (non imm=
une) et celle
de type II (immune)<sup>(5)</sup>.<span style=3D'mso-spacerun:yes'>&nbsp; <=
/span><st1:PersonName
ProductID=3D"La TIH" w:st=3D"on">La TIH</st1:PersonName> type I appara&icir=
c;t
rapidement apr&egrave;s le d&eacute;but de l&#8217;h&eacute;parine soit dans
les 12 &agrave; 24 premi&egrave;res heures<sup>(5)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Le pr&eacute;sent texte ne traiter=
a pas
de <st1:PersonName ProductID=3D"La TIH" w:st=3D"on">la TIH</st1:PersonName>=
 type I
puisqu&#8217;elle est &agrave; la fois b&eacute;nigne et r&eacute;versible =
et
qu&#8217;elle ne n&eacute;cessite aucun traitement<sup>(1,5)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span><st1:PersonName ProductID=3D"La TI=
H"
w:st=3D"on">La TIH</st1:PersonName> type II est un processus immunologique =
qui
survient apr&egrave;s la formation d&#8217;anticorps suite &agrave;
l&#8217;administration d&#8217;h&eacute;parine<sup>(5,7)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Le principal antig&egrave;ne est le
complexe form&eacute; entre l&#8217;h&eacute;parine et le facteur plaquetta=
ire
4 (FP4)<sup>(5,6)</sup>. <span style=3D'mso-spacerun:yes'>&nbsp;</span>La l=
iaison
entre ce facteur et l&#8217;h&eacute;parine d&eacute;clenche un changement =
de
conformit&eacute; du FP4 rendant ainsi l&#8217;association h&eacute;parine-=
FP4 &eacute;trang&egrave;re
pour l&#8217;organisme<sup>(5,6)</sup>. <span
style=3D'mso-spacerun:yes'>&nbsp;</span>L&#8217;affinit&eacute; de
l&#8217;h&eacute;parine pour le FP4 d&eacute;pend entre autres du poids
mol&eacute;culaire de l&#8217;h&eacute;parine, de la longueur de sa cha&ici=
rc;ne
ainsi que du degr&eacute; de sulfatation de celle-ci<sup>(5,6,7)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>La formation d&#8217;anticorps dit
&laquo;&nbsp;h&eacute;parine-d&eacute;pendants&nbsp;&raquo;, principalement=
 compos&eacute;e
d&#8217;immunoglobulines G (IgG), est responsable des complications reli&ea=
cute;es
&agrave; <st1:PersonName ProductID=3D"La TIH" w:st=3D"on">la TIH</st1:Perso=
nName><sup>(5)</sup>.
La liaison du complexe h&eacute;parine/FP4 avec les anticorps active les
plaquettes ce qui cause la lib&eacute;ration d&#8217;une quantit&eacute; im=
portante
de microparticules procoagulantes ainsi que d&#8217;une plus grande
quantit&eacute; de FP4, ce qui augmente la g&eacute;n&eacute;ration de
thrombine<sup>(1,3,5,6)</sup>.<span style=3D'mso-spacerun:yes'>&nbsp; </spa=
n><o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman"'>Actuellement,
aucune donn&eacute;e claire n&#8217;est disponible quant aux doses et aux m=
odes
d&#8217;administration les plus susceptibles d&#8217;induire ce genre de
r&eacute;action auto-immune.<span style=3D'mso-spacerun:yes'>&nbsp;
</span>Cependant, de tr&egrave;s faibles doses d&#8217;h&eacute;parine
employ&eacute;es pour le rin&ccedil;age des cath&eacute;ters ont
&eacute;t&eacute; impliqu&eacute;es dans ce type de r&eacute;action<sup>(1)=
</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Les femmes semblent davantage
pr&eacute;dispos&eacute;es &agrave; pr&eacute;senter une TIH en comparaison=
 aux
hommes<sup>(1,6,7)</sup>.<span style=3D'mso-spacerun:yes'>&nbsp; </span>Les
individus avec des polymorphismes impliquant certains r&eacute;cepteurs
&agrave; la surface des plaquettes pourraient &ecirc;tre
g&eacute;n&eacute;tiquement <o:p></o:p></span></p>

</div>

<span style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-fareast-f=
ont-family:
Calibri;mso-ansi-language:FR-CA;mso-fareast-language:EN-US;mso-bidi-languag=
e:
AR-SA'><br clear=3Dall style=3D'page-break-before:always;mso-break-type:sec=
tion-break'>
</span>

<div class=3DSection2>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman"'>pr&eacute;dispos&eacute;s
&agrave; d&eacute;velopper une TIH<sup>(8)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Enfin, certaines situations cliniq=
ues
pr&eacute;disposent les patients au d&eacute;veloppement d&#8217;anticorps
contre l&#8217;h&eacute;parine (contexte chirurgical &gt; m&eacute;dical &g=
t;
obst&eacute;trical)<sup>(1-3,7)</sup>.<span style=3D'mso-spacerun:yes'>&nbs=
p;
</span><o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>Bien qu&#8217;il n&#8217;existe aucun crit&egrav=
e;re
clinique simple et rapide pour permettre de confirmer ou d&#8217;exclure av=
ec
certitude le diagnostic d&#8217;une TIH, il existe quatre
caract&eacute;ristiques permettant aux cliniciens de suspecter une TIH<sup>=
(6,7)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>L&#8217;&eacute;valuation
m&eacute;dicale et clinique de ces quatre caract&eacute;ristiques, &agrave;
l&#8217;aide d&#8217;un score d&#8217;imputabilit&eacute;, appel&eacute; le
score des 4T, permet d&#8217;estimer la probabilit&eacute; (faible,
interm&eacute;diaire, &eacute;lev&eacute;e) d&#8217;une TIH<sup>(2,6,7,9)</=
sup>.
<span style=3D'mso-spacerun:yes'>&nbsp;</span>Le diagnostic repose sur une
collecte d&#8217;informations d&eacute;taill&eacute;es. L&#8217;apparition
d&#8217;une <b>Thrombop&eacute;nie</b> absolue c&#8217;est-&agrave;-dire d&=
#8217;une
diminution du d&eacute;compte plaquettaire &agrave; un niveau inf&eacute;ri=
eur
&agrave; 150 x 10<sup>9</sup>/L ou bien l&#8217;apparition d&#8217;une
thrombop&eacute;nie relative c&#8217;est-&agrave;-dire une chute des plaque=
ttes
sup&eacute;rieure ou &eacute;gale &agrave; 50% de la valeur initiale est g&=
eacute;n&eacute;ralement
le premier signe clinique de l&#8217;apparition d&#8217;une TIH.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Le <b>Temps</b> &eacute;coul&eacut=
e;
entre le d&eacute;but de l&#8217;administration de l&#8217;h&eacute;parine =
et la
diminution du d&eacute;compte plaquettaire est l&#8217;une des
caract&eacute;ristiques importantes permettant de mettre en &eacute;vidence=
 le
d&eacute;veloppement d&#8217;une TIH.<span style=3D'mso-spacerun:yes'>&nbsp;
</span>G&eacute;n&eacute;ralement, <st1:PersonName ProductID=3D"La TIH" w:s=
t=3D"on">la
 TIH</st1:PersonName> appara&icirc;t entre le jour 5 et le jour 14, ce que
l&#8217;on appelle une TIH typique.<span style=3D'mso-spacerun:yes'>&nbsp;
</span>Ce syndrome peut parfois appara&icirc;tre tr&egrave;s rapidement
apr&egrave;s le d&eacute;but de l&#8217;h&eacute;parine soit dans les heure=
s ou
les jours suivant son initiation, c&#8217;est ce que l&#8217;on appelle <st=
1:PersonName
ProductID=3D"La TIH" w:st=3D"on">la TIH</st1:PersonName> pr&eacute;coce.<sp=
an
style=3D'mso-spacerun:yes'>&nbsp; </span>Cette derni&egrave;re se
d&eacute;veloppe g&eacute;n&eacute;ralement chez les patients ayant
&eacute;t&eacute; r&eacute;cemment expos&eacute;s &agrave;
l&#8217;h&eacute;parine c&#8217;est-&agrave;-dire ayant re&ccedil;u des dos=
es d&#8217;h&eacute;parine
dans les cent jours pr&eacute;c&eacute;dant l&#8217;&eacute;v&eacute;nement=
.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Il existe &eacute;galement une TIH
tardive, quoique beaucoup plus rare, qui se manifeste entre le jour 9 et le
jour 40 apr&egrave;s l&#8217;arr&ecirc;t de l&#8217;h&eacute;parine<sup>(1,=
2,7,10)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>L&#8217;apparition de <b>Thrombose=
s</b>
ou d&#8217;autres manifestations cliniques atypiques telles que des
l&eacute;sions ou des n&eacute;croses cutan&eacute;es au site d&#8217;injec=
tion
et/ou d&#8217;une r&eacute;action syst&eacute;mique aigu&euml; post-injecti=
on d&#8217;un
bolus IV d&#8217;h&eacute;parine (fi&egrave;vre, frissons, naus&eacute;es,
vomissements, diarrh&eacute;es, hypertension, tachycardie, etc.) ou bien la
survenue d&#8217;une gangr&egrave;ne sont souvent caract&eacute;ristiques du
d&eacute;veloppement d&#8217;une TIH<sup>(1-3,10)</sup>. <span
style=3D'mso-spacerun:yes'>&nbsp;</span>Ces diff&eacute;rentes manifestatio=
ns
peuvent &ecirc;tre d&eacute;couvertes avant ou parfois en m&ecirc;me temps =
que la
mise en &eacute;vidence de <st1:PersonName ProductID=3D"La TIH" w:st=3D"on"=
>la TIH</st1:PersonName><sup>(1,2,10)</sup>.
La derni&egrave;re caract&eacute;ristique permettant aux cliniciens de susp=
ecter
une TIH est l&#8217;absence de toutes <b>autres</b> causes autant
m&eacute;dicales que m&eacute;dicamenteuses pouvant entra&icirc;ner
l&#8217;apparition d&#8217;une thrombop&eacute;nie<sup>(1,2,6)</sup>. Lorsq=
ue
la probabilit&eacute; de pr&eacute;senter une TIH, d&eacute;termin&eacute;e=
 &agrave;
l&#8217;aide du score des 4T, est interm&eacute;diaire ou &eacute;lev&eacut=
e;e,
des tests biologiques tels que des tests immunoenzymatiques et parfois m&ec=
irc;me
des tests fonctionnels peuvent &ecirc;tre demand&eacute;s afin de venir
renforcer ou r&eacute;futer le diagnostic suspect&eacute;<sup>(2,5-7)</sup>=
.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Le test ELISA, un test
immunoenzymatique, est le test le plus accessible et le plus fr&eacute;quem=
ment
utilis&eacute; dans les &eacute;tablissements de sant&eacute; du Qu&eacute;=
bec<sup>(2)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Ce test, en plus d&#8217;&ecirc;tre
facile &agrave; utiliser, a une tr&egrave;s bonne sensibilit&eacute; mais u=
ne pi&egrave;tre
sp&eacute;cificit&eacute; en raison de la d&eacute;tection &agrave; la fois=
 des
IgG, des IgM et des IgA<sup>(2,5,6)</sup>.<span style=3D'mso-spacerun:yes'>=
&nbsp;
</span>Les tests fonctionnels comme le test d&#8217;agr&eacute;gation
plaquettaire ou le test de lib&eacute;ration de la s&eacute;rotonine
radiomarqu&eacute;e sont plus rarement utilis&eacute;s en clinique puisqu&#=
8217;ils
ne sont disponibles que dans certains laboratoires sp&eacute;cialis&eacute;=
s.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Ces tests offrent par contre, une
tr&egrave;s grande sp&eacute;cificit&eacute;<sup>(2,5)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp;&nbsp;&nbsp; </span><o:p></o:p></span></p>

</div>

<span style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-fareast-f=
ont-family:
Calibri;mso-ansi-language:FR-CA;mso-fareast-language:EN-US;mso-bidi-languag=
e:
AR-SA;mso-bidi-font-weight:bold'><br clear=3Dall style=3D'page-break-before=
:auto;
mso-break-type:section-break'>
</span>

<div class=3DSection3>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b><span style=3D'font-size:14.0pt;font-family:=
"Times New Roman"'>Traitement
/ Pharmacologie<o:p></o:p></span></b></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>Tout d&#8217;abord, qu&#8217;il y ait
pr&eacute;sence ou non de complications thrombotiques, lorsqu&#8217;une TIH=
 est
mod&eacute;r&eacute;ment ou fortement suspect&eacute;e ou que le diagnostic=
 est
confirm&eacute;, le principe fondamental est de cesser toute forme
d&#8217;h&eacute;parine<sup>(2,3,6,7,9-11)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Le changement d&#8217;une
h&eacute;parine non fractionn&eacute;e pour une h&eacute;parine de faible p=
oids
mol&eacute;culaire ou &agrave; l&#8217;inverse n&#8217;est pas
recommand&eacute;, puisqu&#8217;il existe un risque significatif de r&eacut=
e;action
crois&eacute;e entre ces deux types d&#8217;h&eacute;parine<sup>(1,2,5,6,9)=
</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Le simple fait de cesser
l&#8217;h&eacute;parine n&#8217;enraye pas la &laquo;&nbsp;g&eacute;n&eacut=
e;ration
de thrombine&nbsp;&raquo; ni le risque thromboembolique associ&eacute; &agr=
ave;
<st1:PersonName ProductID=3D"La TIH" w:st=3D"on">la TIH</st1:PersonName><su=
p>(3,5-7,9,11)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Le risque thrombotique persiste
plusieurs jours, voire semaines, apr&egrave;s l&#8217;arr&ecirc;t de
l&#8217;h&eacute;parine et ce, malgr&eacute; la normalisation du
d&eacute;compte plaquettaire<sup>(2)</sup>. Ainsi, plusieurs accidents
thrombotiques surviennent dans les 30 jours suivant le diagnostic de TIH et=
 ce,
malgr&eacute; l&#8217;arr&ecirc;t de toute forme d&#8217;h&eacute;parine ai=
nsi
que le retour &agrave; la num&eacute;risation normale des plaquettes</span>=
<sup><span
style=3D'font-size:12.0pt;font-family:"Times New Roman"'>(2,4,7,11)</span><=
/sup><span
style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-bidi-font-weigh=
t:
bold'>.<span style=3D'mso-spacerun:yes'>&nbsp; </span>Au cours de la phase
aigu&euml; de <st1:PersonName ProductID=3D"La TIH" w:st=3D"on">la TIH</st1:=
PersonName>,
la warfarine peut exacerber l&#8217;&eacute;tat
d&#8217;hypercoagulabilit&eacute; de <st1:PersonName ProductID=3D"La TIH" w=
:st=3D"on">la
 TIH</st1:PersonName> par son inhibition sur la prot&eacute;ine C et
pr&eacute;dispose au d&eacute;veloppement de thromboses microvasculaires qui
occasionnent de la n&eacute;crose cutan&eacute;e et des gangr&egrave;nes
veineuses des membres, c&#8217;est pourquoi elle est contre-indiqu&eacute;e=
<sup>(5-7,9,12)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Si la warfarine est d&eacute;j&agr=
ave;
d&eacute;but&eacute;e au moment de l&#8217;apparition de <st1:PersonName
ProductID=3D"La TIH" w:st=3D"on">la TIH</st1:PersonName>, son effet doit &e=
circ;tre
imm&eacute;diatement renvers&eacute; &agrave; l&#8217;aide de son antidote,=
 la
vitamine K<sup>(1,7)</sup>.<span style=3D'mso-spacerun:yes'>&nbsp; </span>U=
ne
anticoagulation syst&eacute;mique alternative &agrave; dose
th&eacute;rapeutique doit &ecirc;tre d&eacute;but&eacute;e le plus rapideme=
nt
possible afin de r&eacute;duire la production de thrombine et ainsi diminuer
les risques d&#8217;apparition de thrombose ainsi que la mortalit&eacute;/m=
orbidit&eacute;
subs&eacute;quente<sup>(1-3,5,6,9-12)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Il n&#8217;est donc pas
n&eacute;cessaire d&#8217;attendre le r&eacute;sultat du test ELISA avant de
d&eacute;buter l&#8217;anticoagulant alternatif.<span
style=3D'mso-spacerun:yes'>&nbsp; </span><o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>Au Canada, quatre m&eacute;dicaments sont
actuellement approuv&eacute;s comme alternative &agrave;
l&#8217;h&eacute;parine lors d&#8217;apparition d&#8217;une TIH soit la
danaparo&iuml;de, la l&eacute;pirudine, l&#8217;argatroban et la
bivalirudine.<span style=3D'mso-spacerun:yes'>&nbsp; </span>Compte tenu
qu&#8217;aucune &eacute;tude prospective comparative entre les
diff&eacute;rentes mol&eacute;cules n&#8217;est disponible &agrave; ce jour=
, le
choix de l&#8217;anticoagulation de substitution repose sur
l&#8217;&eacute;valuation des caract&eacute;ristiques cliniques du patient
(recours possible &agrave; une proc&eacute;dure invasive, dysfonction de
certains organes, risque de saignement, pr&eacute;sence de thrombose), de la
pharmacocin&eacute;tique et de la pharmacodynamie de ces diff&eacute;rents
agents, de la disponibilit&eacute; et du co&ucirc;t de ceux-ci ainsi que de
l&#8217;exp&eacute;rience du prescripteur avec ces mol&eacute;cules<sup>(1,=
2,9)</sup>.
<span style=3D'mso-spacerun:yes'>&nbsp;</span>Les principales
caract&eacute;ristiques de ces diff&eacute;rents anticoagulants alternatifs=
 sont
pr&eacute;sent&eacute;es dans le tableau I.<o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><u><span style=3D'font-size:12.0pt;font-family:=
"Times New Roman";
mso-bidi-font-weight:bold'>Danaparo&iuml;de<o:p></o:p></span></u></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>Le danaparo&iuml;de, un h&eacute;parino&iuml;de =
de
faible poids mol&eacute;culaire, est un puissant inhibiteur du facteur Xa e=
t est,
&agrave; un degr&eacute; moindre, un inhibiteur de la thrombine<sup>(1,2)</=
sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Bien que l&#8217;apparition d&#821=
7;une
r&eacute;action crois&eacute;e entre le danaparo&iuml;de et les anticorps &=
laquo;&nbsp;h&eacute;parine
d&eacute;pendants&nbsp;&raquo; soit possible, la probabilit&eacute;
d&#8217;apparition de cette r&eacute;action reste malgr&eacute; tout faible
(environ 3%) et se pr&eacute;sente g&eacute;n&eacute;ralement au cours de la
premi&egrave;re semaine de traitement avec le danaparo&iuml;de<sup>(1,2,6,1=
3)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span><o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>Un dosage de l&#8217;anti-Xa doit &ecirc;tre
effectu&eacute; rapidement apr&egrave;s l&#8217;administration des perfusio=
ns
acc&eacute;l&eacute;r&eacute;es afin de d&eacute;terminer si<o:p></o:p></sp=
an></p>

</div>

<span style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-fareast-f=
ont-family:
Calibri;mso-ansi-language:FR-CA;mso-fareast-language:EN-US;mso-bidi-languag=
e:
AR-SA;mso-bidi-font-weight:bold'><br clear=3Dall style=3D'page-break-before=
:always;
mso-break-type:section-break'>
</span>

<div class=3DSection4>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'><span style=3D'mso-spacerun:yes'>&nbsp;</span>des
bolus suppl&eacute;mentaires doivent &ecirc;tre administr&eacute;s au patie=
nt<sup>(1)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Les perfusions
acc&eacute;l&eacute;r&eacute;es doivent &ecirc;tre suivies d&#8217;une
perfusion de maintien qui sera ajust&eacute;e en fonction des r&eacute;sult=
ats obtenus
des niveaux sanguins de l&#8217;anti-Xa<sup>(1)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Il est recommand&eacute;
d&#8217;effectuer un dosage de l&#8217;anti-Xa &agrave; toutes les 24 heure=
s au
cours de l&#8217;administration de la perfusion de maintien afin
d&#8217;ajuster ad&eacute;quatement la dose de cette perfusion<sup>(1)</sup=
>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>La formule sanguine compl&egrave;t=
e ainsi
que la cr&eacute;atinine doivent &eacute;galement &ecirc;tre dos&eacute;es
&eacute;tant donn&eacute; les risques possibles de saignements et
l&#8217;&eacute;limination r&eacute;nale de cette mol&eacute;cule<sup>(1,14=
)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Les doses de danaparo&iuml;de doiv=
ent
&ecirc;tre ajust&eacute;es en insuffisance r&eacute;nale en raison de
l&#8217;&eacute;limination r&eacute;nale de cette mol&eacute;cule.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Lorsque l&#8217;anticoagulation av=
ec le
danaparo&iuml;de est stable, c&#8217;est-&agrave;-dire que les r&eacute;sul=
tats
de l&#8217;anti-Xa se retrouvent &agrave; l&#8217;int&eacute;rieur de
l&#8217;intervalle th&eacute;rapeutique, les doses subs&eacute;quentes peuv=
ent
&ecirc;tre donn&eacute;es par injection sous-cutan&eacute;e deux fois par j=
our
plut&ocirc;t que par voie IV (188U/h en perfusion IV &eacute;quivaut &agrav=
e;
2250U deux fois par jour par voie sous-cutan&eacute;e)<sup>(1)</sup>. <span
style=3D'mso-spacerun:yes'>&nbsp;</span><o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>Le danaparo&iuml;de, lorsque donn&eacute; &agrav=
e;
dose th&eacute;rapeutique, semble, aussi efficace que les inhibiteurs direc=
ts
de la thrombine pour r&eacute;duire les risques de complications
thromboemboliques reli&eacute;s &agrave; <st1:PersonName ProductID=3D"La TI=
H"
w:st=3D"on">la TIH</st1:PersonName><sup>(1,9)</sup>. <span
style=3D'mso-spacerun:yes'>&nbsp;</span>Cette mol&eacute;cule permet de
r&eacute;duire le nombre d&#8217;apparition de nouvelles complications
thrombotiques, d&#8217;amputation et permet &eacute;galement de diminuer la
mortalit&eacute; sans augmentation significative des saignements majeurs<su=
p>(1,5,9)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Le danaparo&iuml;de est
l&#8217;alternative &agrave; privil&eacute;gier lorsqu&#8217;une TIH est
suspect&eacute;e chez un patient pour lequel aucune proc&eacute;dure invasi=
ve
n&#8217;est envisag&eacute;e en raison de son long temps de demi-vie et de =
son
co&ucirc;t inf&eacute;rieur<sup>(9)</sup>.<span style=3D'mso-spacerun:yes'>=
&nbsp;
</span><span style=3D'mso-spacerun:yes'>&nbsp;&nbsp;&nbsp;</span><span
style=3D'mso-spacerun:yes'>&nbsp;</span><o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><u><span style=3D'font-size:12.0pt;font-family:=
"Times New Roman";
mso-bidi-font-weight:bold'>Inhibiteurs directs de la thrombine<o:p></o:p></=
span></u></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>La l&eacute;pirudine, un analogue recombinant de
l&#8217;hirudine, l&#8217;argatroban ainsi que la bivalirudine sont tous des
inhibiteurs directs de la thrombine qui inhibent &agrave; la fois la thromb=
ine
libre et celle li&eacute;e au caillot rendant ainsi inactive la thrombine du
caillot</span><sup><span style=3D'font-size:12.0pt;font-family:"Times New R=
oman"'>(1-7,9,15,16)</span></sup><span
style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-bidi-font-weigh=
t:
bold'>.<span style=3D'mso-spacerun:yes'>&nbsp; </span>L&#8217;argatroban et=
 la
bivalirudine inhibent la thrombine de fa&ccedil;on r&eacute;versible</span>=
<sup><span
style=3D'font-size:12.0pt;font-family:"Times New Roman"'>(1-4,6,9)</span></=
sup><span
style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-bidi-font-weigh=
t:
bold'>.<span style=3D'mso-spacerun:yes'>&nbsp; </span>&Agrave; l&#8217;inve=
rse,
le l&eacute;pirudine inhibe plut&ocirc;t la thrombine de mani&egrave;re
irr&eacute;versible</span><sup><span style=3D'font-size:12.0pt;font-family:=
"Times New Roman"'>(1,2,4,7,9)</span></sup><span
style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-bidi-font-weigh=
t:
bold'>.<span style=3D'mso-spacerun:yes'>&nbsp; </span>Le caract&egrave;re
irr&eacute;versible de sa liaison avec la thrombine augmente le risque
th&eacute;orique de saignement associ&eacute; &agrave; la l&eacute;pirudine=
<sup>(2,7)</sup>.
Cependant, le risque de saignement &agrave; la fois mineur ou majeur est un
effet secondaire possible avec tous les inhibiteurs directs de la thrombine,
quoique de loin plus fr&eacute;quent avec la l&eacute;pirudine<sup>(1,3,14-=
17)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Un suivi &eacute;troit de la formu=
le
sanguine compl&egrave;te et des saignements sont conseill&eacute;s pour tous
les patients qui re&ccedil;oivent un inhibiteur direct de la thrombine<sup>=
(10,17)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Le temps de c&eacute;phaline
activ&eacute;e (TCA), une mesure de l&#8217;intensit&eacute; de
l&#8217;anticoagulation, doit &eacute;galement &ecirc;tre suivi pour tous l=
es
inhibiteurs directs.<span style=3D'mso-spacerun:yes'>&nbsp; </span>Cependan=
t, la
fr&eacute;quence des suivis ainsi que les valeurs de TCA vis&eacute;es vari=
ent
entre les diff&eacute;rentes mol&eacute;cules.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Contrairement au danaparo&iuml;de,=
 les
inhibiteurs directs de la thrombine ne poss&egrave;dent pas de r&eacute;act=
ion immunologique
crois&eacute;e avec l&#8217;h&eacute;parine<sup>(2,6,13)</sup>. <o:p></o:p>=
</span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><u><span style=3D'font-size:12.0pt;font-family:=
"Times New Roman";
mso-bidi-font-weight:bold'>L&eacute;pirudine<o:p></o:p></span></u></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>&Eacute;tant donn&eacute; l&#8217;&eacute;limina=
tion
r&eacute;nale de cette mol&eacute;cule, la vitesse de perfusion doit &ecirc=
;tre
r&eacute;duite lorsque la cr&eacute;atinine est sup&eacute;rieure &agrave; =
90</span><span
style=3D'font-size:12.0pt;font-family:Symbol;mso-ascii-font-family:"Times N=
ew Roman";
mso-hansi-font-family:"Times New Roman";mso-char-type:symbol;mso-symbol-fon=
t-family:
Symbol;mso-bidi-font-weight:bold'><span style=3D'mso-char-type:symbol;mso-s=
ymbol-font-family:
Symbol'>m</span></span><span style=3D'font-size:12.0pt;font-family:"Times N=
ew Roman";
mso-bidi-font-weight:bold'>mol/L et celle-ci doit &ecirc;tre suivie <o:p></=
o:p></span></p>

</div>

<span style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-fareast-f=
ont-family:
Calibri;mso-ansi-language:FR-CA;mso-fareast-language:EN-US;mso-bidi-languag=
e:
AR-SA;mso-bidi-font-weight:bold'><br clear=3Dall style=3D'page-break-before=
:auto;
mso-break-type:section-break'>
</span>

<div class=3DSection5>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>r&eacute;guli&egrave;rement<sup>(1,9)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Le TCA doit &ecirc;tre suivi 2 &ag=
rave;
4 heures apr&egrave;s l&#8217;administration de la premi&egrave;re dose de
l&eacute;pirudine ainsi qu&#8217;apr&egrave;s chaque changement de dose<sup=
>(1,3,7,9,11,16)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Le TCA doit &eacute;galement &ecir=
c;tre
mesur&eacute; &agrave; toutes les quatre heures jusqu&#8217;&agrave;
stabilisation puis une fois par jour par la suite<sup>(1,3,7,9,16)</sup>.<s=
pan
style=3D'mso-spacerun:yes'>&nbsp; </span><span
style=3D'mso-spacerun:yes'>&nbsp;</span>L&#8217;administration de
l&eacute;pirudine g&eacute;n&egrave;re, chez environ 30% des patients, une
formation d&#8217;anticorps antihirudine d&egrave;s le quatri&egrave;me jou=
r de
traitement ce qui rend critique une seconde administration de l&eacute;piru=
dine
chez un patient ayant &eacute;t&eacute; expos&eacute; ant&eacute;rieurement
&agrave; ce m&eacute;dicament<sup>(2,9,16)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Bien que la production d&#8217;ant=
icorps
antihirudine n&#8217;affecte pas l&#8217;efficacit&eacute; de la
l&eacute;pirudine et ne semble pas corr&eacute;ler avec l&#8217;apparition =
de
toxicit&eacute;, cette production d&#8217;anticorps semble parfois prolonger
son effet th&eacute;rapeutique et occasionner une augmentation du TCA lors
d&#8217;une dur&eacute;e de traitement sup&eacute;rieure &agrave; cinq jour=
s<sup>(2,9,13,16)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>La l&eacute;pirudine ne doit, en a=
ucun
cas, &agrave; moins de thrombose mena&ccedil;ant un membre ou la vie du pat=
ient,
&ecirc;tre administr&eacute;e par bolus IV &eacute;tant donn&eacute; la
possibilit&eacute; de r&eacute;action anaphylactique, quoique tr&egrave;s p=
eu fr&eacute;quente<sup>(1,2,9)</sup>.
<span style=3D'mso-spacerun:yes'>&nbsp;</span>L&#8217;immunog&eacute;nicit&=
eacute;
associ&eacute;e avec l&#8217;administration de l&eacute;pirudine ainsi que =
sa
difficult&eacute; d&#8217;emploi en cas d&#8217;insuffisance r&eacute;nale
m&ecirc;me tr&egrave;s l&eacute;g&egrave;re repr&eacute;sentent les
probl&egrave;mes majeurs reli&eacute;s &agrave; son utilisation<sup>(4,6,7,=
9)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>L&#8217;administration de ce
m&eacute;dicament lors d&#8217;une TIH suspect&eacute;e ou confirm&eacute;e,
permet de r&eacute;duire la survenue de nouveaux &eacute;v&eacute;nements
thrombotiques, le risque d&#8217;amputation ainsi que la mortalit&eacute;
associ&eacute;s &agrave; <st1:PersonName ProductID=3D"La TIH" w:st=3D"on">l=
a TIH</st1:PersonName></span><sup><span
style=3D'font-size:12.0pt;font-family:"Times New Roman"'>(2,4,5-7,9)</span>=
</sup><span
style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-bidi-font-weigh=
t:
bold'>.<o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><u><span style=3D'font-size:12.0pt;font-family:=
"Times New Roman";
mso-bidi-font-weight:bold'><o:p><span style=3D'text-decoration:none'>&nbsp;=
</span></o:p></span></u></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><u><span style=3D'font-size:12.0pt;font-family:=
"Times New Roman";
mso-bidi-font-weight:bold'>Argatroban<o:p></o:p></span></u></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>L&#8217;&eacute;limination h&eacute;patique de
l&#8217;argatroban en fait un agent plus s&eacute;curitaire lors insuffisan=
ce
r&eacute;nale<sup>(1)</sup>. <span style=3D'mso-spacerun:yes'>&nbsp;</span>=
Le
temps de c&eacute;phaline activ&eacute;e doit &ecirc;tre mesur&eacute; entre
deux heures et quatre heures apr&egrave;s le d&eacute;but de la perfusion
initiale puis apr&egrave;s chaque changement de doses par la suite<sup>(9,1=
1,18)</sup>.
Le d&eacute;but d&#8217;action tr&egrave;s rapide de l&#8217;argatroban ain=
si
que son court temps de demi-vie permet donc d&#8217;obtenir une anticoagula=
tion
rapide et flexible<sup>(1,17)</sup>.<span style=3D'mso-spacerun:yes'>&nbsp;
</span>L&#8217;argatroban abaisse de fa&ccedil;on significative le taux de
mortalit&eacute;, le taux d&#8217;amputation ainsi que le nombre de nouveaux
&eacute;v&eacute;nements thrombotiques</span><sup><span style=3D'font-size:=
12.0pt;
font-family:"Times New Roman"'>(2,4,6)</span></sup><span style=3D'font-size=
:12.0pt;
font-family:"Times New Roman";mso-bidi-font-weight:bold'>.<o:p></o:p></span=
></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><u><span style=3D'font-size:12.0pt;font-family:=
"Times New Roman";
mso-bidi-font-weight:bold'>Bivalirudine<o:p></o:p></span></u></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>La bivalirudine est une mol&eacute;cule
int&eacute;ressante chez les patients souffrant &agrave; la fois <o:p></o:p=
></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>d&#8217;insuffisance r&eacute;nale et
h&eacute;patique puisque cette mol&eacute;cule poss&egrave;de un court temp=
s de
demi-vie ainsi qu&#8217;une faible &eacute;limination r&eacute;nale<sup>(3)=
</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>En effet, la bivalirudine est
&eacute;limin&eacute;e &agrave; 80% par clivage prot&eacute;olytique au niv=
eau
sanguin et &agrave; 20% par les reins<sup>(3,5,9,11,15)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp;&nbsp; </span><o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><u><span style=3D'font-size:12.0pt;font-family:=
"Times New Roman";
mso-bidi-font-weight:bold'>Prise en charge de <st1:PersonName ProductID=3D"=
La TIH"
w:st=3D"on">la TIH</st1:PersonName><o:p></o:p></span></u></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>La dur&eacute;e de traitement avec
l&#8217;anticoagulant alternatif ainsi que l&#8217;utilisation
subs&eacute;quente d&#8217;un anticoagulant oral varie selon que le patient=
 ait
ou non pr&eacute;sent&eacute; un &eacute;v&eacute;nement thrombotique<sup>(=
2,9)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Bien que le risque thrombotique re=
ste
&eacute;lev&eacute; pour 2 &agrave; 4 semaines apr&egrave;s le d&eacute;but=
 du
traitement alternatif, lorsque les patients ont pr&eacute;sent&eacute; une
thrombop&eacute;nie isol&eacute;e, l&#8217;anticoagulant alternatif &agrave;
dose th&eacute;rapeutique doit &ecirc;tre administr&eacute; au moins
jusqu&#8217;au retour du d&eacute;compte plaquettaire &agrave; sa valeur de
base ou jusqu&#8217;&agrave; un niveau normal (&gt;150 x 10<sup>9</sup>/L)<=
sup>(1,2,9)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Un traitement suppl&eacute;mentaire
d&#8217;un mois avec la warfarine serait sans doute plus s&eacute;curitaire=
<sup>(2)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Lorsque les patients ont pr&eacute=
;sent&eacute;,
en plus de la diminution de <o:p></o:p></span></p>

</div>

<span style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-fareast-f=
ont-family:
Calibri;mso-ansi-language:FR-CA;mso-fareast-language:EN-US;mso-bidi-languag=
e:
AR-SA;mso-bidi-font-weight:bold'><br clear=3Dall style=3D'page-break-before=
:auto;
mso-break-type:section-break'>
</span>

<div class=3DSection6>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>plaquettes, un &eacute;v&eacute;nement thromboti=
que,
l&#8217;anticoagulant alternatif doit &ecirc;tre suivi d&#8217;une transiti=
on
vers la warfarine lors du retour du d&eacute;compte plaquettaire aux valeurs
normales (&gt;150 x 10<sup>9</sup>/L)<sup>(1,2,5-7,9,12,13)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp;&nbsp; </span>La warfarine doit alors &eci=
rc;tre
d&eacute;but&eacute;e &agrave; faible dose et doit chevaucher, pour un mini=
mum
de 5 jours, l&#8217;anticoagulant alternatif jusqu&#8217;&agrave; ce que le
rapport normalis&eacute; international (RNI) soit th&eacute;rapeutique pour=
 au
moins 48 heures<sup>(1,2,5,9,12)</sup>.<span style=3D'mso-spacerun:yes'>&nb=
sp;
</span>Bien que la dur&eacute;e optimale de l&#8217;anticoagulation ne soit=
 pas
clairement &eacute;tablie, la warfarine doit g&eacute;n&eacute;ralement
&ecirc;tre poursuivie pour une dur&eacute;e de 3 &agrave; 6 mois lorsque les
patients ont pr&eacute;sent&eacute; un &eacute;v&eacute;nement thromboembol=
ique<sup>(2,9)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Bien que tous les inhibiteurs dire=
cts de
la thrombine puissent provoquer une &eacute;l&eacute;vation du RNI, cet eff=
et
est de loin plus fr&eacute;quent et plus important avec l&#8217;argatroban<=
sup>(7,18)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Cependant, malgr&eacute; une
augmentation importante du RNI avec l&#8217;argatroban, aucune augmentation=
 de
l&#8217;activit&eacute; anticoagulante syst&eacute;mique n&#8217;a
&eacute;t&eacute; not&eacute;e et il ne semble pas y avoir d&#8217;interact=
ion
r&eacute;elle avec la prise de warfarine<sup>(7,9)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Par contre, lorsque l&#8217;argatr=
oban
est administr&eacute; de fa&ccedil;on concomitante avec la warfarin, un RNI
&agrave; <st1:metricconverter ProductID=3D"4 a" w:st=3D"on">4 a</st1:metric=
converter>
&eacute;t&eacute; d&eacute;montr&eacute; &eacute;quivalent &agrave; un RNI
entre 2 et 3 avec la warfarine seule<sup>(18)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Il est donc recommand&eacute;
d&#8217;attendre l&#8217;obtention d&#8217;une INR &agrave; 4 avant de cess=
er
l&#8217;argatroban<sup>(12)</sup>.<span style=3D'mso-spacerun:yes'>&nbsp;
</span>Cependant, contrairement aux inhibiteurs directs de la thrombine, le
danaparo&iuml;de n&#8217;a aucun effet sur l&#8217;RNI<sup>(1)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span><o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'><o:p>&nbsp;</o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman";
mso-bidi-font-weight:bold'>Peu importe l&#8217;anticoagulant alternatif
utilis&eacute;, un suivi des plaquettes est requis afin de s&#8217;assurer
d&#8217;un retour du d&eacute;compte plaquettaire &agrave; un niveau normal
(g&eacute;n&eacute;ralement apparent entre le jour 4 et le jour 14 suivant
l&#8217;arr&ecirc;t de l&#8217;h&eacute;parine)<sup>(2,5)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Cependant, en l&#8217;absence
d&#8217;am&eacute;lioration apr&egrave;s trois jours de traitement avec un
anticoagulant alternatif, un changement de mol&eacute;cule est
recommand&eacute;.<o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b><span style=3D'font-size:14.0pt;font-family:=
"Times New Roman"'><o:p>&nbsp;</o:p></span></b></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b><span style=3D'font-size:14.0pt;font-family:=
"Times New Roman"'><o:p>&nbsp;</o:p></span></b></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b><span style=3D'font-size:14.0pt;font-family:=
"Times New Roman"'>Pr&eacute;vention<o:p></o:p></span></b></p>

<p class=3DMsoNormal style=3D'text-align:justify;line-height:normal'><span
style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-bidi-font-weigh=
t:
bold'>Bien que plusieurs &eacute;tudes d&eacute;montrent que le risque de
d&eacute;velopper une TIH est inf&eacute;rieur avec les HFPM comparativement
&agrave; HNF, aucun guide de pratique ne recommande l&#8217;utilisation
universelle d&#8217;un type d&#8217;h&eacute;parine puisque le choix de
l&#8217;une ou l&#8217;autre des h&eacute;parines repose sur plusieurs
consid&eacute;rations cliniques<sup>(1)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Ainsi, la fa&ccedil;on la plus sim=
ple et
efficace de pr&eacute;venir les complications importantes secondaires &agra=
ve;
l&#8217;apparition d&#8217;une TIH est d&#8217;effectuer une mesure des
plaquettes de base et un suivi &eacute;troit des plaquettes chez tous les
patients qui d&eacute;butent une h&eacute;parine et ce, peu importe le type
d&#8217;h&eacute;parine administr&eacute;<sup>(5,6,10)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>De plus, limiter la dur&eacute;e du
traitement h&eacute;parinique en r&eacute;&eacute;valuant
r&eacute;guli&egrave;rement la n&eacute;cessit&eacute; de poursuivre la
thromboprophylaxie ou le traitement &agrave; l&#8217;h&eacute;parine est un
autre moyen de pr&eacute;venir ou du moins de r&eacute;duire le risque
d&#8217;apparition d&#8217;une TIH<sup>(5)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>De plus, un diagnostic rapide ainsi
qu&#8217;une prise en charge ad&eacute;quate est n&eacute;cessaire afin de
r&eacute;duire les r&eacute;percussions d&eacute;sastreuses autant sur le p=
lan
m&eacute;dical que financier li&eacute;es &agrave; un mauvais diagnostic ou
&agrave; une prise en charge tardive ou inad&eacute;quate<sup>(6)</sup>.<sp=
an
style=3D'mso-spacerun:yes'>&nbsp;&nbsp; </span><o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b><span style=3D'font-size:14.0pt;font-family:=
"Times New Roman"'><o:p>&nbsp;</o:p></span></b></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b><span style=3D'font-size:14.0pt;font-family:=
"Times New Roman"'>Conclusion<o:p></o:p></span></b></p>

<p class=3DMsoNormal style=3D'text-align:justify;line-height:normal'><span
style=3D'font-size:12.0pt;font-family:"Times New Roman"'>La thrombop&eacute=
;nie
induite par l&#8217;h&eacute;parine est une r&eacute;action
m&eacute;dicamenteuse ind&eacute;sirable grave qui peut occasionner
d&#8217;importantes complications qui elles, peuvent menacer un <o:p></o:p>=
</span></p>

</div>

<span style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-fareast-f=
ont-family:
Calibri;mso-ansi-language:FR-CA;mso-fareast-language:EN-US;mso-bidi-languag=
e:
AR-SA'><br clear=3Dall style=3D'page-break-before:auto;mso-break-type:secti=
on-break'>
</span>

<div class=3DSection7>

<p class=3DMsoNormal style=3D'text-align:justify;line-height:normal'><span
style=3D'font-size:12.0pt;font-family:"Times New Roman"'>membre ou la vie du
patient<sup>(1,2,5,11)</sup>.<span style=3D'mso-spacerun:yes'>&nbsp; </span=
>Bien
que le diagnostic soit parfois complexe &agrave; poser &eacute;tant
donn&eacute; la subtilit&eacute; de la pr&eacute;sentation clinique de cette
complication ainsi que des multiples causes cliniques pouvant entra&icirc;n=
er
une thrombop&eacute;nie, la rapidit&eacute; avec laquelle le diagnostic est
envisag&eacute; ainsi qu&#8217;une prise en charge rapide et ad&eacute;quate
sont essentielles afin de minimiser les complications reli&eacute;es &agrav=
e; <st1:PersonName
ProductID=3D"La TIH" w:st=3D"on">la TIH</st1:PersonName><sup>(6)</sup>.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Les inhibiteurs directs de la thro=
mbine
ainsi que le danaparo&iuml;de sont utilis&eacute;s comme traitement alterna=
tif
&agrave; l&#8217;h&eacute;parine en fonction des diff&eacute;rentes
caract&eacute;ristiques cliniques du patient et des diff&eacute;rentes part=
icularit&eacute;s
propres &agrave; chacun de ces agents.<span style=3D'mso-spacerun:yes'>&nbs=
p;
</span>Par contre, des &eacute;tudes comparatives sont n&eacute;cessaires a=
fin
de pouvoir statuer de fa&ccedil;on claire sur le choix des
mol&eacute;cules.<span style=3D'mso-spacerun:yes'>&nbsp; </span>Dans le fut=
ur, il
serait &eacute;galement souhaitable que d&#8217;autres &eacute;tudes vienne=
nt
clarifier la dur&eacute;e de traitement avec ces agents afin de pr&eacute;c=
iser
davantage le traitement et d&#8217;assurer une couverture optimale des pati=
ents
pr&eacute;sentant une TIH puisque peu de donn&eacute;es sont disponibles
jusqu&#8217;&agrave; maintenant sur le sujet. <o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b><span style=3D'font-size:14.0pt;font-family:=
"Times New Roman"'><o:p>&nbsp;</o:p></span></b></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b><span style=3D'font-size:14.0pt;font-family:=
"Times New Roman"'>Pr&eacute;par&eacute;
par<o:p></o:p></span></b></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman"'>Krystel
Poitras-Saulnier, B.pharm., M. Sc.* <o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal;mso-layout-grid-align:none;text-autospace:none'>=
<i><span
style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-fareast-font-fa=
mily:
SimSun;mso-fareast-language:ZH-CN'>*Mme Poitras-Saulnier &eacute;tait
r&eacute;sidente au CHUQ - </span></i><i><span style=3D'font-size:12.0pt;
font-family:"Times New Roman"'>H&ocirc;pital St-Fran&ccedil;ois d&#8217;Ass=
ise
au moment de la r&eacute;daction</span></i><i><span style=3D'font-size:12.0=
pt;
font-family:"Times New Roman";mso-fareast-font-family:SimSun;mso-fareast-la=
nguage:
ZH-CN'>.<o:p></o:p></span></i></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal;mso-layout-grid-align:none;text-autospace:none'>=
<span
style=3D'font-size:10.0pt;font-family:"Times New Roman"'><o:p>&nbsp;</o:p><=
/span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b><span style=3D'font-size:14.0pt;font-family:=
"Times New Roman"'>R&eacute;vis&eacute;
par&nbsp;<o:p></o:p></span></b></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><span style=3D'font-size:12.0pt;font-family:"Ti=
mes New Roman"'>Fran&ccedil;ois
Brouillette, B.Pharm., M.Sc.., pharmacien au </span><span style=3D'font-siz=
e:
12.0pt;font-family:"Times New Roman";mso-fareast-font-family:SimSun;mso-far=
east-language:
ZH-CN'>CHUQ</span><span style=3D'font-size:12.0pt;font-family:"Times New Ro=
man"'>
</span><span style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-fa=
reast-font-family:
SimSun;mso-fareast-language:ZH-CN'>- </span><span style=3D'font-size:12.0pt;
font-family:"Times New Roman"'>H&ocirc;pital St-Fran&ccedil;ois d&#8217;Ass=
ise<o:p></o:p></span></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-family:=
"Times New Roman"'><o:p>&nbsp;</o:p></span></b></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b style=3D'mso-bidi-font-weight:normal'><span
style=3D'font-size:14.0pt;font-family:"Times New Roman"'><o:p>&nbsp;</o:p><=
/span></b></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b style=3D'mso-bidi-font-weight:normal'><span
style=3D'font-size:14.0pt;font-family:"Times New Roman"'><o:p>&nbsp;</o:p><=
/span></b></p>

<p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;text-=
align:
justify;line-height:normal'><b style=3D'mso-bidi-font-weight:normal'><span
style=3D'font-size:14.0pt;font-family:"Times New Roman"'>R&eacute;f&eacute;=
rences<o:p></o:p></span></b></p>

<ol style=3D'margin-top:0cm' start=3D1 type=3D1>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     style=3D'font-size:12.0pt;font-family:"Times New Roman"'>Warkentin TE,
     Greinacher A, Koster A et coll.<span style=3D'mso-spacerun:yes'>&nbsp;
     </span></span><span lang=3DEN-CA style=3D'font-size:12.0pt;font-family=
:"Times New Roman";
     mso-ansi-language:EN-CA'>Treatment and Prevention of Heparin-Induced
     Thrombocytopenia&nbsp;: <st1:place w:st=3D"on"><st1:PlaceName w:st=3D"=
on">American</st1:PlaceName>
      <st1:PlaceType w:st=3D"on">College</st1:PlaceType></st1:place> of Che=
st
     Physicians Evidence-Based Clinical Practice Guidelines.<span
     style=3D'mso-spacerun:yes'>&nbsp; </span>Chest 2008;133:340-80. </span=
><span
     style=3D'font-size:12.0pt;font-family:"Times New Roman"'><o:p></o:p></=
span></li>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     lang=3DEN-CA style=3D'font-size:12.0pt;font-family:"Times New Roman";
     mso-ansi-language:EN-CA'>Arepally GM, Ortel TL.<span
     style=3D'mso-spacerun:yes'>&nbsp; </span>Heparine-Induced
     Thrombocytopenia.<span style=3D'mso-spacerun:yes'>&nbsp; </span>N Engl=
 J Med
     Aug 2006;355:809-17.<o:p></o:p></span></li>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     lang=3DEN-CA style=3D'font-size:12.0pt;font-family:"Times New Roman";
     mso-ansi-language:EN-CA'>Seybert AL, Coons JC, Zerumsky K.<span
     style=3D'mso-spacerun:yes'>&nbsp; </span>Treatment of Heparine-Induced
     Thrombocytopenia: Is There a Role for Bivalirudine?<span
     style=3D'mso-spacerun:yes'>&nbsp; </span>Pharmacotherapy 2006;26(2):22=
9-41.<o:p></o:p></span></li>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     style=3D'font-size:12.0pt;font-family:"Times New Roman"'>Deitcher SR.,=
<span
     style=3D'mso-spacerun:yes'>&nbsp; </span>Traitements anti-agr&eacute;g=
ant,
     anticoagulant et fibrinolytique.<span style=3D'mso-spacerun:yes'>&nbsp;
     </span>Dans: Kasper DL, Braunwald E, Fauci A et coll. Harrison Princip=
es
     de m&eacute;decine interne.<span style=3D'mso-spacerun:yes'>&nbsp; </s=
pan></span><span
     lang=3DEN-US style=3D'font-size:12.0pt;font-family:"Times New Roman";
     mso-ansi-language:EN-US'>16i&egrave;me &eacute;dition. <st1:place w:st=
=3D"on"><st1:City
      w:st=3D"on">Paris</st1:City></st1:place>. Flammarion
     M&eacute;decine-Sciences. 2006:103;688-9.</span><span style=3D'font-si=
ze:
     12.0pt;font-family:"Times New Roman"'><o:p></o:p></span></li>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     lang=3DEN-CA style=3D'font-size:12.0pt;font-family:"Times New Roman";
     mso-ansi-language:EN-CA'>Ahmed I, Majeed A, Powell R.<span
     style=3D'mso-spacerun:yes'>&nbsp; </span>Heparin induced thrombocytope=
nia:
     diagnosis and management update.<span style=3D'mso-spacerun:yes'>&nbsp;
     </span>Postgrad Med J 2007;83:575-82.<o:p></o:p></span></li>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     style=3D'font-size:12.0pt;font-family:"Times New Roman"'>Castelli R,
     Cassinerio E, Cappellini MD et coll.<span style=3D'mso-spacerun:yes'>&=
nbsp;
     </span></span><span lang=3DEN-CA style=3D'font-size:12.0pt;font-family=
:"Times New Roman";
     mso-ansi-language:EN-CA'>Heparin Induced Thrombocytopenia&nbsp;:
     Pathogenetic, Clinical, Diagnostic and Therapeutic Aspects.<span
     style=3D'mso-spacerun:yes'>&nbsp; </span>Cardiovascular and Haematolog=
ical
     Disorders-Drugs Targets 2007;7:153-62.<span
     style=3D'mso-spacerun:yes'>&nbsp; </span><o:p></o:p></span></li>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     lang=3DEN-CA style=3D'font-size:12.0pt;font-family:"Times New Roman";
     mso-ansi-language:EN-CA'>Warkentin TE. Heparine-Induced Thrombocytopen=
ia.
     Dis Mon 2005;51:141-8.<o:p></o:p></span></li>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     style=3D'font-size:12.0pt;font-family:"Times New Roman"'>Gruel Y, Poup=
lard
     C, Lasne D, et coll. </span><span lang=3DEN-CA style=3D'font-size:12.0=
pt;
     font-family:"Times New Roman";mso-ansi-language:EN-CA'>The homozygous
     FcgammaRIIIa-158V genotype is a risk factor for heparin-induced<o:p></=
o:p></span></li>
</ol>

</div>

<span lang=3DEN-CA style=3D'font-size:12.0pt;font-family:"Times New Roman";
mso-fareast-font-family:Calibri;mso-ansi-language:EN-CA;mso-fareast-languag=
e:
EN-US;mso-bidi-language:AR-SA'><br clear=3Dall style=3D'page-break-before:a=
lways;
mso-break-type:section-break'>
</span>

<div class=3DSection8>

<p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bottom=
:0cm;
margin-left:36.0pt;margin-bottom:.0001pt;text-align:justify;line-height:nor=
mal'><span
lang=3DEN-CA style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-an=
si-language:
EN-CA'><span style=3D'mso-spacerun:yes'>&nbsp;</span>thrombocytopenia in pa=
tients
with antibodies to heparin-platelet factor 4 complexes.<span
style=3D'mso-spacerun:yes'>&nbsp; </span>Blood 2004;104:2791-3.<o:p></o:p><=
/span></p>

<ol style=3D'margin-top:0cm' start=3D9 type=3D1>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     lang=3DEN-CA style=3D'font-size:12.0pt;font-family:"Times New Roman";
     mso-ansi-language:EN-CA'>Dager WE, Dougherty JA, Nguyen PH, et coll.<s=
pan
     style=3D'mso-spacerun:yes'>&nbsp; </span>Heparin-induced thrombocytope=
nia.
     Pharmacotherapy 2007;27(4):564-87.<o:p></o:p></span></li>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     lang=3DEN-CA style=3D'font-size:12.0pt;font-family:"Times New Roman";
     mso-ansi-language:EN-CA'>Spinler SA.<span style=3D'mso-spacerun:yes'>&=
nbsp;
     </span>New Concepts in Heparin-Induced Thrombocytopenia: diagnosis and
     management.<span style=3D'mso-spacerun:yes'>&nbsp; </span>J Thromb
     Thrombolysis 2006;21(1):17-21.<o:p></o:p></span></li>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     lang=3DEN-CA style=3D'font-size:12.0pt;font-family:"Times New Roman";
     mso-ansi-language:EN-CA'>Dang CH, Durkalski VL, Nappi JM.<span
     style=3D'mso-spacerun:yes'>&nbsp; </span>Evaluation of Treatment with =
Direct
     Thrombin Inhibitors in Patients with Heparin-Induced
     Thrombocytopenia.<span style=3D'mso-spacerun:yes'>&nbsp;&nbsp;
     </span>Pharmacotherapy 2006; 26(4):461-8.<o:p></o:p></span></li>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     lang=3DEN-CA style=3D'font-size:12.0pt;font-family:"Times New Roman";
     mso-ansi-language:EN-CA'>Bartholomeu JR.<span
     style=3D'mso-spacerun:yes'>&nbsp; </span>Transition to an Oral Anticoa=
gulant
     in Patients With Heparin-Induced Thrombocytopenia.<span
     style=3D'mso-spacerun:yes'>&nbsp; </span>Chest 2005;127(Suppl 2):27S-3=
4S.<o:p></o:p></span></li>
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t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     lang=3DEN-CA style=3D'font-size:12.0pt;font-family:"Times New Roman";
     mso-ansi-language:EN-CA'>Hassell K.<span style=3D'mso-spacerun:yes'>&n=
bsp;
     </span>The Management of Patients With Heparin-Induced Thrombocytopenia
     Who Require Anticoagulant Therapy.<span style=3D'mso-spacerun:yes'>&nb=
sp;
     </span>Chest 2005;127(2 Suppl):1S-8S.<o:p></o:p></span></li>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     style=3D'font-size:12.0pt;font-family:"Times New Roman"'>Organon.<span
     style=3D'mso-spacerun:yes'>&nbsp; </span>Monographie du danaparo&iuml;=
de
     (Orgaran<sup>MD</sup>). </span><span lang=3DEN-CA style=3D'font-size:1=
2.0pt;
     font-family:"Times New Roman";mso-ansi-language:EN-CA'>2007.<o:p></o:p=
></span></li>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-fareast-la=
nguage:
     FR-CA'>Oryx Pharmaceuticals Inc. </span><span style=3D'font-size:12.0p=
t;
     font-family:"Times New Roman"'>Monographie de la bivalirudine (Angioma=
x<sup>MD</sup>).
     Mississauga, Ontario; 2008.<o:p></o:p></span></li>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     style=3D'font-size:12.0pt;font-family:"Times New Roman"'>Bayer Inc.<sp=
an
     style=3D'mso-spacerun:yes'>&nbsp; </span>Monographie de la l&eacute;pi=
rudine
     (Refludan<sup>MD</sup>).<span style=3D'mso-spacerun:yes'>&nbsp;
     </span>Toronto, Ontario; 2007.<o:p></o:p></span></li>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     style=3D'font-size:12.0pt;font-family:"Times New Roman"'>Laboratoire
     Abbott.<span style=3D'mso-spacerun:yes'>&nbsp; </span>Monographie de
     l&#8217;argatroban (Novastan<sup>MD</sup>). 2006.<o:p></o:p></span></l=
i>
 <li class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
     justify;line-height:normal;mso-list:l18 level1 lfo20;tab-stops:list 36=
.0pt'><span
     style=3D'font-size:12.0pt;font-family:"Times New Roman"'>Yeh RW, Jang =
IK Argatroban&nbsp;:
     Update. Am Heart J 2006;151(6)&nbsp;:1131-8.</span><i style=3D'mso-bid=
i-font-style:
     normal'><u><span style=3D'font-size:10.0pt;font-family:"Times New Roma=
n";
     mso-bidi-font-weight:bold'><o:p></o:p></span></u></i></li>
</ol>

</div>

<span style=3D'font-size:12.0pt;font-family:"Times New Roman";mso-fareast-f=
ont-family:
Calibri;mso-ansi-language:FR-CA;mso-fareast-language:EN-US;mso-bidi-languag=
e:
AR-SA'><br clear=3Dall style=3D'page-break-before:auto;mso-break-type:secti=
on-break'>
</span>

<div class=3DSection9>

<p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bottom=
:0cm;
margin-left:18.0pt;margin-bottom:.0001pt;text-align:justify;line-height:nor=
mal'><span
style=3D'font-size:12.0pt;font-family:"Times New Roman"'><o:p>&nbsp;</o:p><=
/span></p>

<p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bottom=
:0cm;
margin-left:18.0pt;margin-bottom:.0001pt;text-align:justify;line-height:nor=
mal'><i
style=3D'mso-bidi-font-style:normal'><u><span style=3D'font-size:10.0pt;fon=
t-family:
"Times New Roman";mso-bidi-font-weight:bold'>Toute reproduction, en tout ou=
 en
partie, de la publication ne doit &ecirc;tre faite que sous autorisation
&eacute;crite du pharmacien coordonateur du Centre d&#8217;information sur =
le
m&eacute;dicament.<o:p></o:p></span></u></i></p>

</div>

<u><span style=3D'font-size:10.0pt;line-height:200%;font-family:"Times New =
Roman";
mso-fareast-font-family:Calibri;mso-ansi-language:FR-CA;mso-fareast-languag=
e:
EN-US;mso-bidi-language:AR-SA;mso-bidi-font-weight:bold'><br clear=3Dall
style=3D'page-break-before:always;mso-break-type:section-break'>
</span></u>

<div class=3DSection10></div>

<span style=3D'font-size:10.0pt;line-height:200%;font-family:"Times New Rom=
an";
mso-fareast-font-family:Calibri;mso-ansi-language:FR-CA;mso-fareast-languag=
e:
EN-US;mso-bidi-language:AR-SA;mso-bidi-font-weight:bold'><br clear=3Dall
style=3D'page-break-before:auto;mso-break-type:section-break'>
</span>

<div class=3DSection11>

<p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-botto=
m:.0001pt;
text-align:center;line-height:200%'><span style=3D'font-size:10.0pt;line-he=
ight:
200%;font-family:"Times New Roman";mso-bidi-font-weight:bold'><o:p>&nbsp;</=
o:p></span></p>

<p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-botto=
m:.0001pt;
text-align:center;line-height:200%'><span style=3D'font-size:10.0pt;line-he=
ight:
200%;font-family:"Times New Roman";mso-bidi-font-weight:bold'>Tableau I<o:p=
></o:p></span></p>

<table class=3DMsoNormalTable border=3D1 cellspacing=3D0 cellpadding=3D0
 style=3D'border-collapse:collapse;border:none;mso-border-alt:solid #404040=
 1.0pt;
 mso-yfti-tbllook:480;mso-padding-alt:0cm 5.4pt 0cm 5.4pt;mso-border-inside=
h:
 1.0pt solid #404040'>
 <tr style=3D'mso-yfti-irow:0;mso-yfti-firstrow:yes'>
  <td width=3D636 colspan=3D5 valign=3Dtop style=3D'width:477.2pt;border:so=
lid #404040 1.0pt;
  background:black;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:200%'><b><span style=3D'font-size:10.0pt;
  line-height:200%;font-family:"Times New Roman";color:white'>Tableau compa=
ratif
  des anticoagulants alternatifs &agrave; l&#8217;h&eacute;parine<sup>(1,3,=
6,11,14-18)</sup></span></b><b><span
  style=3D'font-size:14.0pt;line-height:200%;font-family:"Times New Roman";
  color:white'><o:p></o:p></span></b></p>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><b><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";color:white'><o:p>&nbsp;</o:p></span></b></=
p>
  </td>
 </tr>
 <tr style=3D'mso-yfti-irow:1'>
  <td width=3D127 valign=3Dtop style=3D'width:95.4pt;border-top:none;border=
-left:
  solid #404040 1.0pt;border-bottom:solid #404040 1.0pt;border-right:none;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'><o:p>&nbsp;</o:p></span></b></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>Danaparo&iuml;de<o:p></o:p></span></b></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>L&eacute;pirudine<o:p></o:p></span></b></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>Argatroban<o:p></o:p></span></b></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border-top:none;borde=
r-left:
  none;border-bottom:solid #404040 1.0pt;border-right:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>Bivalirudine<o:p></o:p></span></b></p>
  </td>
 </tr>
 <tr style=3D'mso-yfti-irow:2'>
  <td width=3D127 valign=3Dtop style=3D'width:95.4pt;border-top:none;border=
-left:
  solid #404040 1.0pt;border-bottom:solid #404040 1.0pt;border-right:none;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>Indication officielle au Canada<o:p></o:p></span></b><=
/p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>Oui<o:p></o:p></=
span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>Oui<o:p></o:p></=
span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>Oui<o:p></o:p></=
span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border-top:none;borde=
r-left:
  none;border-bottom:solid #404040 1.0pt;border-right:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>Oui (ICP)<o:p></=
o:p></span></p>
  </td>
 </tr>
 <tr style=3D'mso-yfti-irow:3'>
  <td width=3D127 valign=3Dtop style=3D'width:95.4pt;border-top:none;border=
-left:
  solid #404040 1.0pt;border-bottom:solid #404040 1.0pt;border-right:none;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>M&eacute;canisme d&#8217;action<o:p></o:p></span></b><=
/p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>Anti-Xa<o:p></o:=
p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>Inhibiteur direct de la thrombine<o:p></o:p></=
span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>Inhibiteur direct de la thrombine<o:p></o:p></=
span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border-top:none;borde=
r-left:
  none;border-bottom:solid #404040 1.0pt;border-right:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>Inhibiteur direc=
t de
  la thrombine (r&eacute;versible)<o:p></o:p></span></p>
  </td>
 </tr>
 <tr style=3D'mso-yfti-irow:4'>
  <td width=3D127 valign=3Dtop style=3D'width:95.4pt;border-top:none;border=
-left:
  solid #404040 1.0pt;border-bottom:solid #404040 1.0pt;border-right:none;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>D&eacute;but d&#8217;action<o:p></o:p></span></b></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>2-5 heures<o:p><=
/o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>15-30 minutes<o:=
p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>Imm&eacute;diate=
ment<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border-top:none;borde=
r-left:
  none;border-bottom:solid #404040 1.0pt;border-right:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>Imm&eacute;diate=
ment<o:p></o:p></span></p>
  </td>
 </tr>
 <tr style=3D'mso-yfti-irow:5'>
  <td width=3D127 valign=3Dtop style=3D'width:95.4pt;border-top:none;border=
-left:
  solid #404040 1.0pt;border-bottom:solid #404040 1.0pt;border-right:none;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>Temps de demi-vie<o:p></o:p></span></b></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>24 heures<o:p></=
o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>75 &agrave;
  80minutes<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>40-50minutes<o:p=
></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border-top:none;borde=
r-left:
  none;border-bottom:solid #404040 1.0pt;border-right:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>25 minutes<o:p><=
/o:p></span></p>
  </td>
 </tr>
 <tr style=3D'mso-yfti-irow:6'>
  <td width=3D127 valign=3Dtop style=3D'width:95.4pt;border-top:none;border=
-left:
  solid #404040 1.0pt;border-bottom:solid #404040 1.0pt;border-right:none;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>Voie d&#8217;&eacute;limination majoritaire<o:p></o:p>=
</span></b></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>R&eacute;nale<o:=
p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>R&eacute;nale<o:=
p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>H&eacute;pato-bi=
liaire<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border-top:none;borde=
r-left:
  none;border-bottom:solid #404040 1.0pt;border-right:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal align=3Dcenter style=3D'margin-bottom:0cm;margin-bot=
tom:.0001pt;
  text-align:center;line-height:normal'><span style=3D'font-size:10.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>Clivage
  prot&eacute;olytique et m&eacute;tabolisme r&eacute;nale <o:p></o:p></spa=
n></p>
  </td>
 </tr>
 <tr style=3D'mso-yfti-irow:7'>
  <td width=3D127 valign=3Dtop style=3D'width:95.4pt;border-top:none;border=
-left:
  solid #404040 1.0pt;border-bottom:solid #404040 1.0pt;border-right:none;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>Suivi<o:p></o:p></span></b></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>Anti-Xa&nbsp;: 0,5 &agrave; 0,8 U/mL<o:p></o:p=
></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>TCA&nbsp;: 1,5 &agrave; 2,5 fois la valeur nor=
male<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>TCA&nbsp;: 1,5 et 3 fois la valeur normale<o:p=
></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border-top:none;borde=
r-left:
  none;border-bottom:solid #404040 1.0pt;border-right:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>TCA&nbsp;: 1,5 &agrave; 2,5 fois la valeur nor=
male<o:p></o:p></span></p>
  </td>
 </tr>
 <tr style=3D'mso-yfti-irow:8'>
  <td width=3D127 valign=3Dtop style=3D'width:95.4pt;border-top:none;border=
-left:
  solid #404040 1.0pt;border-bottom:solid #404040 1.0pt;border-right:none;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>Influence sur RNI<o:p></o:p></span></b></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>Non<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>Augmentation possible<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>Augmentation importante<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border-top:none;borde=
r-left:
  none;border-bottom:solid #404040 1.0pt;border-right:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>Augmentation possible<o:p></o:p></span></p>
  </td>
 </tr>
 <tr style=3D'mso-yfti-irow:9'>
  <td width=3D127 valign=3Dtop style=3D'width:95.4pt;border-top:none;border=
-left:
  solid #404040 1.0pt;border-bottom:solid #404040 1.0pt;border-right:none;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>Voie d&#8217;administration et doses<o:p></o:p></span>=
</b></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>IV<o:p></o:p></span></p>
  <p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bott=
om:0cm;
  margin-left:10.95pt;margin-bottom:.0001pt;text-indent:-7.1pt;line-height:
  normal;mso-list:l11 level1 lfo5'><![if !supportLists]><span style=3D'font=
-size:
  10.0pt;font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-fa=
mily:
  Symbol;mso-bidi-font-weight:bold'><span style=3D'mso-list:Ignore'>&middot=
;<span
  style=3D'font:7.0pt "Times New Roman"'>&nbsp; </span></span></span><![end=
if]><span
  style=3D'font-size:10.0pt;font-family:"Times New Roman";mso-bidi-font-wei=
ght:
  bold'>Bolus selon le poids<sup>*</sup><o:p></o:p></span></p>
  <p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bott=
om:0cm;
  margin-left:10.95pt;margin-bottom:.0001pt;text-align:justify;text-indent:
  -7.1pt;line-height:normal;mso-list:l11 level1 lfo5'><![if !supportLists]>=
<span
  style=3D'font-size:10.0pt;font-family:Symbol;mso-fareast-font-family:Symb=
ol;
  mso-bidi-font-family:Symbol;mso-bidi-font-weight:bold'><span
  style=3D'mso-list:Ignore'>&middot;<span style=3D'font:7.0pt "Times New Ro=
man"'>&nbsp;
  </span></span></span><![endif]><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman";mso-bidi-font-weight:bold'>400 U/h x4 heures<o:p></o:p>=
</span></p>
  <p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bott=
om:0cm;
  margin-left:10.95pt;margin-bottom:.0001pt;text-align:justify;text-indent:
  -7.1pt;line-height:normal;mso-list:l11 level1 lfo5'><![if !supportLists]>=
<span
  style=3D'font-size:10.0pt;font-family:Symbol;mso-fareast-font-family:Symb=
ol;
  mso-bidi-font-family:Symbol;mso-bidi-font-weight:bold'><span
  style=3D'mso-list:Ignore'>&middot;<span style=3D'font:7.0pt "Times New Ro=
man"'>&nbsp;
  </span></span></span><![endif]><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman";mso-bidi-font-weight:bold'>300 U/h x4 heures<o:p></o:p>=
</span></p>
  <p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bott=
om:0cm;
  margin-left:10.95pt;margin-bottom:.0001pt;text-indent:-7.1pt;line-height:
  normal;mso-list:l11 level1 lfo5'><![if !supportLists]><span style=3D'font=
-size:
  10.0pt;font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-fa=
mily:
  Symbol;mso-bidi-font-weight:bold'><span style=3D'mso-list:Ignore'>&middot=
;<span
  style=3D'font:7.0pt "Times New Roman"'>&nbsp; </span></span></span><![end=
if]><span
  style=3D'font-size:10.0pt;font-family:"Times New Roman";mso-bidi-font-wei=
ght:
  bold'>200 U/h (perfusion de maintien ajust&eacute;e en fonction de
  l&#8217;anti-Xa<o:p></o:p></span></p>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;lin=
e-height:
  normal'><span style=3D'font-size:10.0pt;font-family:"Times New Roman";
  mso-bidi-font-weight:bold'>S/C&nbsp;: Voir texte<span style=3D'background=
:aqua;
  mso-highlight:aqua'><o:p></o:p></span></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>IV seulement<o:p></o:p></span></p>
  <p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bott=
om:0cm;
  margin-left:7.6pt;margin-bottom:.0001pt;text-indent:-7.05pt;line-height:n=
ormal;
  mso-list:l10 level1 lfo9'><![if !supportLists]><span style=3D'font-size:1=
0.0pt;
  font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:Sy=
mbol;
  mso-bidi-font-weight:bold'><span style=3D'mso-list:Ignore'>&middot;<span
  style=3D'font:7.0pt "Times New Roman"'>&nbsp; </span></span></span><![end=
if]><span
  style=3D'font-size:10.0pt;font-family:"Times New Roman";mso-bidi-font-wei=
ght:
  bold'>Perfusion continue<o:p></o:p></span></p>
  <p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bott=
om:0cm;
  margin-left:7.6pt;margin-bottom:.0001pt;text-indent:-7.05pt;line-height:n=
ormal;
  mso-list:l19 level1 lfo6'><![if !supportLists]><span style=3D'font-size:1=
0.0pt;
  font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:Sy=
mbol;
  mso-bidi-font-weight:bold'><span style=3D'mso-list:Ignore'>&middot;<span
  style=3D'font:7.0pt "Times New Roman"'>&nbsp; </span></span></span><![end=
if]><span
  style=3D'font-size:10.0pt;font-family:"Times New Roman";mso-bidi-font-wei=
ght:
  bold'>0.10 mg/kg/h (cr&eacute;atinine &lt;90 </span><span style=3D'font-s=
ize:
  10.0pt;font-family:Symbol;mso-ascii-font-family:"Times New Roman";mso-han=
si-font-family:
  "Times New Roman";mso-char-type:symbol;mso-symbol-font-family:Symbol;
  mso-bidi-font-weight:bold'><span style=3D'mso-char-type:symbol;mso-symbol=
-font-family:
  Symbol'>m</span></span><span style=3D'font-size:10.0pt;font-family:"Times=
 New Roman";
  mso-bidi-font-weight:bold'>mol/L)<o:p></o:p></span></p>
  <p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bott=
om:0cm;
  margin-left:7.6pt;margin-bottom:.0001pt;text-indent:-7.05pt;line-height:n=
ormal;
  mso-list:l19 level1 lfo6'><![if !supportLists]><span style=3D'font-size:1=
0.0pt;
  font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:Sy=
mbol;
  mso-bidi-font-weight:bold'><span style=3D'mso-list:Ignore'>&middot;<span
  style=3D'font:7.0pt "Times New Roman"'>&nbsp; </span></span></span><![end=
if]><span
  style=3D'font-size:10.0pt;font-family:"Times New Roman";mso-bidi-font-wei=
ght:
  bold'>0.05 mg/kg/h (cr&eacute;atinine &gt;90 </span><span style=3D'font-s=
ize:
  10.0pt;font-family:Symbol;mso-ascii-font-family:"Times New Roman";mso-han=
si-font-family:
  "Times New Roman";mso-char-type:symbol;mso-symbol-font-family:Symbol;
  mso-bidi-font-weight:bold'><span style=3D'mso-char-type:symbol;mso-symbol=
-font-family:
  Symbol'>m</span></span><span style=3D'font-size:10.0pt;font-family:"Times=
 New Roman";
  mso-bidi-font-weight:bold'>mol/L)<o:p></o:p></span></p>
  <p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bott=
om:0cm;
  margin-left:7.6pt;margin-bottom:.0001pt;text-align:justify;text-indent:-7=
.05pt;
  line-height:normal'><span style=3D'font-size:10.0pt;font-family:"Times Ne=
w Roman";
  mso-bidi-font-weight:bold'><o:p>&nbsp;</o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>IV seulement<o:p></o:p></span></p>
  <p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bott=
om:0cm;
  margin-left:11.4pt;margin-bottom:.0001pt;text-indent:-11.4pt;line-height:
  normal;mso-list:l17 level1 lfo7'><![if !supportLists]><span style=3D'font=
-size:
  10.0pt;font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-fa=
mily:
  Symbol;mso-bidi-font-weight:bold'><span style=3D'mso-list:Ignore'>&middot=
;<span
  style=3D'font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp; </span></=
span></span><![endif]><span
  style=3D'font-size:10.0pt;font-family:"Times New Roman";mso-bidi-font-wei=
ght:
  bold'>Dose initiale de <span style=3D'mso-spacerun:yes'>&nbsp;&nbsp;</spa=
n>2 </span><span
  style=3D'font-size:10.0pt;font-family:Symbol;mso-ascii-font-family:"Times=
 New Roman";
  mso-hansi-font-family:"Times New Roman";mso-char-type:symbol;mso-symbol-f=
ont-family:
  Symbol;mso-bidi-font-weight:bold'><span style=3D'mso-char-type:symbol;
  mso-symbol-font-family:Symbol'>m</span></span><span style=3D'font-size:10=
.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>g/kg/min en
  perfusion continue<o:p></o:p></span></p>
  <p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bott=
om:0cm;
  margin-left:11.4pt;margin-bottom:.0001pt;text-indent:-11.4pt;line-height:
  normal;mso-list:l17 level1 lfo7'><![if !supportLists]><span style=3D'font=
-size:
  10.0pt;font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-fa=
mily:
  Symbol;mso-bidi-font-weight:bold'><span style=3D'mso-list:Ignore'>&middot=
;<span
  style=3D'font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp; </span></=
span></span><![endif]><span
  style=3D'font-size:10.0pt;font-family:"Times New Roman";mso-bidi-font-wei=
ght:
  bold'>Dose de d&eacute;part de 0,5 </span><span style=3D'font-size:10.0pt;
  font-family:Symbol;mso-ascii-font-family:"Times New Roman";mso-hansi-font=
-family:
  "Times New Roman";mso-char-type:symbol;mso-symbol-font-family:Symbol;
  mso-bidi-font-weight:bold'><span style=3D'mso-char-type:symbol;mso-symbol=
-font-family:
  Symbol'>m</span></span><span style=3D'font-size:10.0pt;font-family:"Times=
 New Roman";
  mso-bidi-font-weight:bold'>g/kg/min en IH mod&eacute;r&eacute;e<o:p></o:p=
></span></p>
  <p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bott=
om:0cm;
  margin-left:11.4pt;margin-bottom:.0001pt;text-indent:-11.4pt;line-height:
  normal;mso-list:l17 level1 lfo7'><![if !supportLists]><span style=3D'font=
-size:
  10.0pt;font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-fa=
mily:
  Symbol;mso-bidi-font-weight:bold'><span style=3D'mso-list:Ignore'>&middot=
;<span
  style=3D'font:7.0pt "Times New Roman"'>&nbsp;&nbsp;&nbsp;&nbsp; </span></=
span></span><![endif]><span
  style=3D'font-size:10.0pt;font-family:"Times New Roman";mso-bidi-font-wei=
ght:
  bold'>Doses moyennes entre 0,5 et <span
  style=3D'mso-spacerun:yes'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;</span>1,2=
 </span><span
  style=3D'font-size:10.0pt;font-family:Symbol;mso-ascii-font-family:"Times=
 New Roman";
  mso-hansi-font-family:"Times New Roman";mso-char-type:symbol;mso-symbol-f=
ont-family:
  Symbol;mso-bidi-font-weight:bold'><span style=3D'mso-char-type:symbol;
  mso-symbol-font-family:Symbol'>m</span></span><span style=3D'font-size:10=
.0pt;
  font-family:"Times New Roman";mso-bidi-font-weight:bold'>g/kg/min<o:p></o=
:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border-top:none;borde=
r-left:
  none;border-bottom:solid #404040 1.0pt;border-right:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>IV seulement<o:p></o:p></span></p>
  <p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bott=
om:0cm;
  margin-left:8.1pt;margin-bottom:.0001pt;text-indent:-7.1pt;line-height:no=
rmal;
  mso-list:l13 level1 lfo8'><![if !supportLists]><span style=3D'font-size:1=
0.0pt;
  font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:Sy=
mbol;
  mso-bidi-font-weight:bold'><span style=3D'mso-list:Ignore'>&middot;<span
  style=3D'font:7.0pt "Times New Roman"'>&nbsp; </span></span></span><![end=
if]><span
  style=3D'font-size:10.0pt;font-family:"Times New Roman";mso-bidi-font-wei=
ght:
  bold'>0,15 &agrave; 0,20 mg/kg/h en perfusion continue<o:p></o:p></span><=
/p>
  </td>
 </tr>
 <tr style=3D'mso-yfti-irow:10'>
  <td width=3D127 valign=3Dtop style=3D'width:95.4pt;border-top:none;border=
-left:
  solid #404040 1.0pt;border-bottom:solid #404040 1.0pt;border-right:none;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>R&eacute;action crois&eacute;e avec
  l&#8217;h&eacute;parine<o:p></o:p></span></b></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>Oui (faible)<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>Non<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>Non<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border-top:none;borde=
r-left:
  none;border-bottom:solid #404040 1.0pt;border-right:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>Non<o:p></o:p></span></p>
  </td>
 </tr>
 <tr style=3D'mso-yfti-irow:11'>
  <td width=3D127 valign=3Dtop style=3D'width:95.4pt;border-top:none;border=
-left:
  solid #404040 1.0pt;border-bottom:solid #404040 1.0pt;border-right:none;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>Immunog&eacute;nicit&eacute;<o:p></o:p></span></b></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>Oui<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>Oui<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>Non<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border-top:none;borde=
r-left:
  none;border-bottom:solid #404040 1.0pt;border-right:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>Non<o:p></o:p></span></p>
  </td>
 </tr>
 <tr style=3D'mso-yfti-irow:12'>
  <td width=3D127 valign=3Dtop style=3D'width:95.4pt;border-top:none;border=
-left:
  solid #404040 1.0pt;border-bottom:solid #404040 1.0pt;border-right:none;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>Antidote<o:p></o:p></span></b></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;lin=
e-height:
  normal'><span style=3D'font-size:10.0pt;font-family:"Times New Roman";
  mso-bidi-font-weight:bold'>Non mais effet partiellement neutralis&eacute;=
 par
  la protamine<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;lin=
e-height:
  normal'><span style=3D'font-size:10.0pt;font-family:"Times New Roman";
  mso-bidi-font-weight:bold'>Non<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;lin=
e-height:
  normal'><span style=3D'font-size:10.0pt;font-family:"Times New Roman";
  mso-bidi-font-weight:bold'>Non<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border-top:none;borde=
r-left:
  none;border-bottom:solid #404040 1.0pt;border-right:solid #404040 1.0pt;
  mso-border-top-alt:solid #404040 1.0pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;lin=
e-height:
  normal'><span style=3D'font-size:10.0pt;font-family:"Times New Roman";
  mso-bidi-font-weight:bold'>Non<o:p></o:p></span></p>
  </td>
 </tr>
 <tr style=3D'mso-yfti-irow:13;mso-yfti-lastrow:yes'>
  <td width=3D127 valign=3Dtop style=3D'width:95.4pt;border-top:none;border=
-left:
  solid #404040 1.0pt;border-bottom:solid #404040 1.0pt;border-right:none;
  mso-border-top-alt:double #404040 2.25pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><b><span style=3D'font-size:10.0pt;font-famil=
y:
  "Times New Roman"'>Co&ucirc;t/jour<o:p></o:p></span></b></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:double #404040 2.25pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>150$<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:double #404040 2.25pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>250$<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border:none;border-bo=
ttom:solid #404040 1.0pt;
  mso-border-top-alt:double #404040 2.25pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>650$<o:p></o:p></span></p>
  </td>
  <td width=3D127 valign=3Dtop style=3D'width:95.45pt;border-top:none;borde=
r-left:
  none;border-bottom:solid #404040 1.0pt;border-right:solid #404040 1.0pt;
  mso-border-top-alt:double #404040 2.25pt;padding:0cm 5.4pt 0cm 5.4pt'>
  <p class=3DMsoNormal style=3D'margin-bottom:0cm;margin-bottom:.0001pt;tex=
t-align:
  justify;line-height:normal'><span style=3D'font-size:10.0pt;font-family:"=
Times New Roman";
  mso-bidi-font-weight:bold'>400-800$<o:p></o:p></span></p>
  </td>
 </tr>
</table>

<p class=3DMsoNormal style=3D'margin-top:0cm;margin-right:0cm;margin-bottom=
:0cm;
margin-left:36.0pt;margin-bottom:.0001pt;text-align:justify;line-height:nor=
mal'><sup><span
style=3D'font-size:10.0pt;font-family:Symbol;mso-ascii-font-family:"Times N=
ew Roman";
mso-hansi-font-family:"Times New Roman";mso-char-type:symbol;mso-symbol-fon=
t-family:
Symbol;mso-bidi-font-weight:bold'><span style=3D'mso-char-type:symbol;mso-s=
ymbol-font-family:
Symbol'>*</span></span></sup><span style=3D'font-size:10.0pt;font-family:"T=
imes New Roman";
mso-bidi-font-weight:bold'>&lt;60kg&nbsp;: 1500 U, 60-75kg&nbsp;: 2250 U,
75-90kg&nbsp;: 3000 U et &gt;90kg&nbsp;: 3750 U, ICP&nbsp;: </span><span
class=3Dapple-style-span><span style=3D'font-size:8.5pt;font-family:Verdana;
color:black'>intervention coronarienne percutan&eacute;e</span></span><span
lang=3DEN-CA style=3D'font-size:12.0pt;font-family:"Times New Roman";backgr=
ound:
aqua;mso-highlight:aqua;mso-ansi-language:EN-CA'><o:p></o:p></span></p>

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<p class=3DMsoFooter style=3D'margin-top:6.0pt;tab-stops:center 216.0pt rig=
ht 463.5pt 526.5pt'><span
style=3D'font-family:"Times New Roman"'>Volume 10, Num&eacute;ro 1<span
style=3D'mso-tab-count:1'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbs=
p;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp; </span>2010<span
style=3D'mso-tab-count:1'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbs=
p;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbs=
p;&nbsp;&nbsp;&nbsp;&nbsp; </span></span><!--[if gte vml 1]><v:shape
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026"
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indowtext 1.0pt;
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<p class=3DMsoHeader style=3D'tab-stops:center 450.0pt right 553.5pt;border=
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mso-border-bottom-alt:solid windowtext .75pt;padding:0cm;mso-padding-alt:0c=
m 0cm 1.0pt 0cm'><span
style=3D'font-family:"Times New Roman"'>Bulletin d&#8217;information du Cen=
tre
d&#8217;information sur le m&eacute;dicament<o:p></o:p></span></p>

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<p class=3DMsoFooter style=3D'margin-top:6.0pt;tab-stops:center 216.0pt rig=
ht 463.5pt 526.5pt'><span
style=3D'font-family:"Times New Roman"'>Volume 10, Num&eacute;ro 1<span
style=3D'mso-tab-count:1'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbs=
p;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp; </span>2010<span
style=3D'mso-tab-count:1'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbs=
p;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbs=
p;&nbsp;&nbsp;&nbsp;&nbsp; </span></span><!--[if gte vml 1]><v:shape
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m 0cm 1.0pt 0cm'><span
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ht 463.5pt 526.5pt'><span
style=3D'font-family:"Times New Roman"'>Volume 10, Num&eacute;ro 1<span
style=3D'mso-tab-count:1'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbs=
p;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp; </span>2010</span><span
style=3D'mso-tab-count:1'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbs=
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nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbs=
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<p class=3DMsoFooter style=3D'margin-top:6.0pt;tab-stops:center 216.0pt rig=
ht 463.5pt 526.5pt'><span
style=3D'font-family:"Times New Roman"'>Volume 10, Num&eacute;ro 1<span
style=3D'mso-tab-count:1'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbs=
p;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp; </span>2010</span><span
style=3D'mso-tab-count:1'>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbs=
p;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbs=
p;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&=
nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; </span><!--[if gte vml 1]><=
v:shape
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</v:shape><![endif]--><!--[if gte mso 9]><xml>
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029"
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