<?xml version="1.0" encoding="ISO-8859-1"?><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance">
<front>
<journal-meta>
<journal-id>1688-423X</journal-id>
<journal-title><![CDATA[Archivos de Medicina Interna]]></journal-title>
<abbrev-journal-title><![CDATA[Arch Med Int]]></abbrev-journal-title>
<issn>1688-423X</issn>
<publisher>
<publisher-name><![CDATA[Sociedad de Medicina Interna del Uruguay]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S1688-423X2011000400004</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Trombofilia y embarazo: Pautas de diagnóstico y tratamiento Pérdida recurrente de embarazo]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Zunino]]></surname>
<given-names><![CDATA[Juan]]></given-names>
</name>
</contrib>
</contrib-group>
<aff id="A">
<institution><![CDATA[,  ]]></institution>
<addr-line><![CDATA[ ]]></addr-line>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>07</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>07</month>
<year>2011</year>
</pub-date>
<volume>33</volume>
<fpage>S5</fpage>
<lpage>S7</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.edu.uy/scielo.php?script=sci_arttext&amp;pid=S1688-423X2011000400004&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.edu.uy/scielo.php?script=sci_abstract&amp;pid=S1688-423X2011000400004&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.edu.uy/scielo.php?script=sci_pdf&amp;pid=S1688-423X2011000400004&amp;lng=en&amp;nrm=iso"></self-uri><kwd-group>
<kwd lng="es"><![CDATA[Embarazo]]></kwd>
<kwd lng="en"><![CDATA[Pregnancy]]></kwd>
<kwd lng="en"><![CDATA[Thrombophilia]]></kwd>
</kwd-group>
</article-meta>
</front><body><![CDATA[ <p style="margin-bottom: 0cm; line-height: 0.64cm; widows: 0; orphans: 0; text-align: center;" lang="es-ES"> <font face="Verdana" style="font-size: 13pt"><i><b>Trombofilia y embarazo    <br>  Pautas de diagn&oacute;stico y tratamiento</b></i></font></p>      <div style="text-align: center;"></div>      <p style="margin-top: 0.2cm; margin-bottom: 0cm; line-height: 0.49cm; widows: 0; orphans: 0; text-align: center;" lang="es-ES"> <font face="Verdana">P&eacute;rdida recurrente de embarazo</font></p>      <div style="text-align: left;"></div>      <p style="margin-top: 0.2cm; margin-bottom: 0cm; line-height: 0.49cm; widows: 0; orphans: 0; text-align: left;" lang="es-ES"></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana" size="2">     <br>  </font><font face="Verdana" color="#000000"><small><b>Dr. Juan Zunino</b></small></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">&nbsp;&nbsp;&nbsp; Se define PRE a tres o m&aacute;s perdidas consecutivas, menores a 20 semanas de gestaci&oacute;n; si bien algunos grupos aceptan 2 o m&aacute;s p&eacute;rdidas</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a name="1."></a><a href="#1">1</a>,<a name="2."></a><a href="#2">2</a>,<a name="3."></a><a href="#3">3</a>)</font></sup><font style="font-size: 10pt;" size="2" face="Verdana">.</font></font><font color="#000000" face="Verdana" size="2"><sup> </sup></font> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">Algunos autores se&ntilde;alan que pueden incluirse p&eacute;rdidas posteriores a 20 semanas</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#3">3</a>)</font></sup><font style="font-size: 10pt;" size="2" face="Verdana">, lo que hace variar la frecuencia de etiolog&iacute;as.</font></font></p>      ]]></body>
<body><![CDATA[<p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana" size="2">     <br>  </font><font face="Verdana" color="#000000"><small><span style="font-weight: bold;">Epidemiolog&iacute;a</span></small><font size="2">    <br>  </font>  <font style="font-size: 10pt;" size="2">&nbsp;&nbsp;&nbsp; Un 15% de mujeres embarazadas presentan una p&eacute;rdida espor&aacute;dica y en un 50 a 60% esta ocurre previamente a la detecci&oacute;n cl&iacute;nica</font></font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#1">1</a>,<a href="#2">2</a>)</font></sup><font style="font-size: 10pt;" size="2" face="Verdana">. Dos p&eacute;rdidas ocurren en 5% de embarazos</font><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a name="4."></a><a href="#4">4</a>,<a name="5."></a><a href="#5">5</a>)</font></sup><font style="font-size: 10pt;" size="2" face="Verdana">. Tres p&eacute;rdidas en 0,4-1% </font><sup> <font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#1">1</a>,<a href="#4">4</a>,<a href="#5">5</a>)</font></sup><font style="font-size: 10pt;" size="2" face="Verdana">.</font></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana" size="2">     <br>  </font>  </p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"></p>      <div style="text-align: left;"><font face="Verdana" color="#000000"><small><b>Etiolog&iacute;a    <br>  </b></small><font style="font-size: 10pt;" size="2">&nbsp;&nbsp;&nbsp; La mayor&iacute;a de p&eacute;rdidas aisladas son debidas a aneuploid&iacute;a fetal espont&aacute;nea</font></font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#2">2</a>)</font></sup><font style="font-size: 10pt;" size="2" face="Verdana">.</font></font><font color="#000000" face="Verdana" size="2"> </font><font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">Las p&eacute;rdidas recurrentes son debidas a causas variadas</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#1">1</a>,<a href="#2">2</a>)</font></sup><font style="font-size: 10pt;" size="2" face="Verdana">:</font></font><font color="#000000" face="Verdana" size="2"> </font><font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">gen&eacute;ticas<b>, </b>autoinmunes, end&oacute;crinas, anat&oacute;micas maternas, infecciosas y trombofilia<b>. </b></font><font face="Verdana" color="#000000">   <font style="font-size: 10pt;" size="2">La frecuencia de las distintas etiolog&iacute;as var&iacute;a seg&uacute;n las series.</font><font size="2"> </font>   <font style="font-size: 10pt;" size="2">Es de se&ntilde;alar que la etiolog&iacute;a es desconocida en 50% o m&aacute;s de los casos</font></font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#1">1</a>,<a href="#2">2</a>,<a href="#4">4</a>,<a href="#5">5</a>)</font></sup></font></div>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana" size="2">     <br>  </font>  </p>      ]]></body>
<body><![CDATA[<p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"></p>      <div style="text-align: left;"><font face="Verdana" color="#000000"><small><b>Diagn&oacute;stico    <br>  </b></small><font style="font-size: 10pt;" size="2">&nbsp;&nbsp;&nbsp; Se acepta que la oportunidad apropiada para iniciar estudios es luego de 2 p&eacute;rdidas</font></font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#1">1</a>,<a href="#2">2</a>)</font></sup></font><font color="#000000" face="Verdana" size="2"> </font><font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">No existe un acuerdo de protocolo de estudio para la PRE</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#1">1</a>-<a href="#3">3</a>,<a name="6."></a><a href="#6">6</a>,<a name="7."></a><a href="#7">7</a>)</font></sup><font style="font-size: 10pt;" size="2" face="Verdana">.</font></font></div>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">Recomendaci&oacute;n<b>: </b>estas pacientes se deben estudiar y tratar en el contexto de un equipo interdisciplinario (obstetra; hemat&oacute;logo; internista, genetista). Debido a que las etiolog&iacute;as de PRE son muy variadas, se sugiere el estudio de las causas gen&eacute;ticas, autoinmunes, endocrinas, anat&oacute;micas maternas, infecciosas, etc., adaptadas a cada paciente en particular; adem&aacute;s de las trombofilias que m&aacute;s adelante se se&ntilde;alan.&nbsp;</font></p>  <font face="Verdana" color="#000000"><small><b>    <br>  Trombofilias</b></small></font><font face="Verdana" size="2"> </font>     <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana" size="2">    <br>  </font>  </p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana" size="2">    <br>  </font>  </p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"></p>      ]]></body>
<body><![CDATA[<div style="text-align: left;"><font face="Verdana" color="#000000"><small><b>Trombofilia adquirida    <br>  </b></small><font style="font-size: 10pt;" size="2">&nbsp;&nbsp; &nbsp;&nbsp; &nbsp; S&iacute;ndrome Antifosfolip&iacute;dico (ver cap&iacute;tulo de SAFE).</font><font size="2">   </font><font style="font-size: 10pt;" size="2">Se recomienda estudio de SAF en PRE<b>.</b></font></font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana"><b>(</b><a href="#1">1</a>,<a href="#2">2</a>,<a name="4-10."></a><a href="#4">4</a>-<a href="#10">10</a>)</font></sup></font></div>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana" size="2">     <br>  </font><font face="Verdana" color="#000000"><small><b>Trombofilia hereditaria</b></small><font size="2">    <br>  </font>  <font style="font-size: 10pt;" size="2">&nbsp;&nbsp;&nbsp; En el estudio nacional sobre Trombofilia y PRE (A. Otero y cols</font></font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a name="11."></a><a href="#11">11</a>)</font></sup><font style="font-size: 10pt;" size="2" face="Verdana">) se constat&oacute; asociaci&oacute;n significativa de p&eacute;rdida recurrente con FVL, Lipo A, MTHFR homocigota, FIIG20210A.</font></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">La Revisi&oacute;n Sistem&aacute;tica de Robertson et al</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a name="12."></a><a href="#12">12</a>)</font></sup></font><font color="#000000" face="Verdana" size="2"> </font><font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">constat&oacute; asociaci&oacute;n significativa de FVL homocigoto y FIIG20210A heterocigoto en p&eacute;rdida temprana, definida como menor a 24 semanas de gestaci&oacute;n. Constat&oacute; asociaci&oacute;n significativa de d&eacute;ficit de PS, FVL y FIIG20210A en p&eacute;rdida tard&iacute;a, definida como mayor a 24 semanas de gestaci&oacute;n. </font> </p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">Persiste pol&eacute;mica respecto al peso de la relaci&oacute;n causal entre TH y p&eacute;rdida de embarazo</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#3">3</a>,<a href="#7">7</a>,<a href="#9">9</a>,<a href="#10">10</a>,<a name="13-16."></a><a href="#13">13</a>-<a href="#16">16</a>)</font></sup></font><font color="#000000" face="Verdana" size="2"> </font><font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">En el trabajo de Robertson y col</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#12">12</a>)</font></sup></font><font color="#000000" face="Verdana" size="2"> </font><font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">se se&ntilde;ala un riesgo absoluto bajo de las anteriores trombofilias hereditarias en la PRE.</font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana">En cuanto al estudio de Trombofilia hereditaria en PRE persiste pol&eacute;mica y discrepancias entre diferentes Gu&iacute;as y Consensos:</font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">El Consenso Latinoamericano 2008 del grupo CLAHT</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a name="17."></a><a href="#17">17</a>)</font></sup><font style="font-size: 10pt;" size="2" face="Verdana">se&ntilde;ala: &ldquo;Cuando una mujer tiene una historia obst&eacute;trica de complicaciones por insuficiencia placentaria deben buscarse causas de trombofilia gen&eacute;tica&rdquo;.</font></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">Las gu&iacute;as Italianas</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#10">10</a>) </font></sup><font style="font-size: 10pt;" size="2" face="Verdana">recomiendan realizar <i>screening</i></font></font><font color="#000000" face="Verdana" size="2"> </font><font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">para trombofilia en mujeres con PRE o MFI Inexplicada. (Grado C*).</font></p>      ]]></body>
<body><![CDATA[<p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">Las Dutch Guidelines</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#7">7</a>)</font></sup></font><font color="#000000" face="Verdana" size="2"> </font><font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">recomiendan estudiar TH (AT, PC, PS, FVL, FII G20210A y factor VIII) &uacute;nicamente en casos de antecedentes de ETEV y/o defectos conocidos de trombofilia en familiares de primer grado, en combinaci&oacute;n con una historia de ETEV.</font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">La Gu&iacute;a del ACCP</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#9">9</a>) </font></sup><font style="font-size: 10pt;" size="2" face="Verdana">2008 no recomienda estudio de TH en PRE.</font></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">La British Guideline</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#16">16</a>) </font></sup><font style="font-size: 10pt;" size="2" face="Verdana">no efect&uacute;a recomendaciones sobre TH en PRE.</font></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana"><font size="2">     <br>  </font><font style="font-size: 10pt;" size="2"><b>Recomendaci&oacute;n</b>    <br>  &nbsp;&nbsp; &nbsp;&nbsp; &nbsp; En PRE menor a 24 semanas de gestaci&oacute;n se recomienda solicitar: FVL y FII G20210A (2B).</font></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana">En PRE mayor a 24 semanas se recomienda solicitar: FVL, FII G20210A y PS (2B).</font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana">Debido a no encontrar claras recomendaciones de estudio se deja en libertad al m&eacute;dico actuante para solicitar otros estudios de trombofilia hereditaria seg&uacute;n cada caso particular.</font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana"><font size="2">     <br>  </font><font style="font-size: 10pt;" size="2"><b>Tratamiento</b>    ]]></body>
<body><![CDATA[<br>  &nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp; PRE y SAFE (ver cap&iacute;tulo de SAFE).</font></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">PRE y TH: Existe pol&eacute;mica respecto al tratamiento de la TH y PRE.</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a name="18."></a><a href="#18">18</a>,<a name="19."></a><a href="#19">19</a>)</font></sup></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">Existen estudios no randomizados vs. placebo que evidencian un beneficio de HBPM en TH y p&eacute;rdida de embarazo</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#3">3</a>,<a name="20."></a><a href="#20">20</a>,<a name="21."></a><a href="#21">21</a>)</font></sup></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">Una Revisi&oacute;n Cochrane</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a name="22."></a><a href="#22">22</a>)</font></sup></font><font color="#000000" face="Verdana" size="2"> </font><font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">de 2010, no constat&oacute; beneficio en el uso de HBPM o AAS en PRE sin presencia de SAFE.</font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">Las gu&iacute;as Italianas</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#10">10</a>)</font></sup></font><font color="#000000" face="Verdana" size="2"> </font><font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">recomiendan: dosis de HBPM profil&aacute;ctica anteparto en mujeres heterocigotas para FVL o FII G20210A y PRE. Y 6 semanas luego del parto. (Grado C*).</font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">ACCP</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#9">9</a>) </font></sup><font style="font-size: 10pt;" size="2" face="Verdana">2008: No indica tratamiento en caso de TH y PRE.</font></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">Dutch Guidelines</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#7">7</a>) </font></sup><font style="font-size: 10pt;" size="2" face="Verdana">2007: no recomiendan tratamiento dado la falta de evidencia.</font></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">British Guideline</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">(<a href="#16">16</a>) </font></sup><font style="font-size: 10pt;" size="2" face="Verdana">2009: no recomiendan tratamiento antitromb&oacute;tico a embarazadas basado en tests de TH.</font></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana">Recomendaci&oacute;n: HBPM profil&aacute;ctica en casos de PRE y documentaci&oacute;n de FVL, FII G20210A y d&eacute;ficit de PS. (3C)</font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana" size="2">     ]]></body>
<body><![CDATA[<br>  </font><font face="Verdana" color="#000000"><small><b>PRE de causa inexplicada</b></small><font size="2">    <br>  </font>  <font style="font-size: 10pt;" size="2">&nbsp;&nbsp;&nbsp; &nbsp;&nbsp;&nbsp; Los estudios ALIFE</font></font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">4</font></sup></font><font color="#000000" face="Verdana" size="2"> </font><font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">y SPIN</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">5</font></sup></font><font color="#000000" face="Verdana" size="2"> </font><font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">del a&ntilde;o 2010, prospectivos y randomizados, evaluaron beneficio de tratamiento en PRE de causa inexplicada.</font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">ALIFE</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">4</font></sup><font style="font-size: 10pt;" size="2" face="Verdana">: AAS aislada o combinada con Nadroparina no mejoraron la tasa de nacidos vivos en comparaci&oacute;n con placebo.</font></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana" color="#000000">SPIN</font><font color="#000000"><sup><font style="font-size: 10pt;" size="2" face="Verdana">5</font></sup><font style="font-size: 10pt;" size="2" face="Verdana">: El uso de AAS y Enoxaparina en mujeres con PRE no tienen beneficio en prevenci&oacute;n de una p&eacute;rdida futura comparado con cuidado fetal intensivo.</font></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana">Es de se&ntilde;alar que estos 2 estudios no descartaron TH para definir PRE de causa inexplicada.</font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana">Recomendaci&oacute;n: no estar&iacute;a indicado el uso de AAS o HBPM en PRE de causa inexplicada (IE).</font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana" size="2">     <br>  </font>  </p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana"><b>*Recomendaciones de PRE consensuadas en PARO (ver anexo)</b></font></p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> </p>      ]]></body>
<body><![CDATA[<p style="margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES">&nbsp;</p>      <p style="margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font size="2" face="Verdana"><b>Palabras clave:</b> Embarazo; Trombofilia.</font></p>      <p style="margin-bottom: 0.35cm;" lang="es-ES"> <font size="2" face="Verdana"><b>Keywords:</b></font><font size="2"><font face="Verdana"> </font> <span style="font-family: Verdana;">Pregnancy; Thrombophilia.</span></font></p>      <p style="margin-bottom: 0.35cm;" lang="es-ES">&nbsp;</p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana" size="2">     <br>  </font>  </p>      <p style="margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" lang="es-ES"> <font style="font-size: 10pt;" size="2" face="Verdana"><b>Bibliograf&iacute;a</b></font></p>      <p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana" size="2">     <br>  </font>  </p>      <!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a name="1"></a><a href="#1.">1</a>. Tulandi T, Al-Fozan H, Lockwood C, Bars V. UpToDate. Definition and etiology of recurrent pregnancy loss. Last literature review version 18.1: Feb 2010</font><!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a name="2"></a><a href="#2.">2.</a> Allison JL, Schust D. Recurrent first trimester pregnancy loss: revised definitions and novel causes. Curr Opin Endocrinol Diabetes Obes 2009; 16:446-450.    </font></p>      <!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a name="3"></a><a href="#3.">3</a>. Carp H. Thrombophilia and Recurrent Pregnancy Loss. Obstet Gynecol Clin N Am 33 2006; 33: 429-442</font><!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a name="4"></a><a href="#4-10.">4</a>. Kaandorp SP, Goddijn M, van der Post JA, Hutten BA, Verhoeve HR, Hamuly&aacute;k K, Mol BW, Folkeringa N, Nahuis M, Papatsonis DN, B&uuml;ller HR, van der Veen F, Middeldorp S. Aspirin plus Heparin or Aspirin Alone in Women with Recurrent Miscarriage. N Engl J Med 2010 Apr 29; 362(17):1586-96.    </font></p>      <!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a name="5"></a><a href="#4-10.">5</a>. Clark P, Walker ID, Langhorne P, Crichton L, Thomson A, Greaves M, Whyte S, Greer IA, Scottish Pregnancy Intervention Study (SPIN) collaborators. SPIN (Scottish Pregnancy Intervention) study: a multicenter, randomized controlled trial of low-molecular-weight heparin and low-dose aspirin in women with recurrent miscarriage. Blood 2010 ;115(21):4162-7.     </font> </p>      <!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a name="6"></a><a href="#4-10.">6</a>. The investigation and treatment of couples with recurrent miscarriage. Royal College of Obstetricians and Gynaecologists.Guideline No 17. Revised May 2003</font><!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a name="7"></a><a href="#4-10.">7</a>. Guideline recurrent miscarriage; The Dutch Society of Obstetrics and Gynaecology (NVOG); 2007 Aug 06. 20p.     </font> </p>      ]]></body>
<body><![CDATA[<!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a name="8"></a><a href="#4-10.">8</a>. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006 Feb;4(2):295-306.     </font> </p>      <!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a name="9"></a><a href="#4-10.">9</a>. Bates SM, Greer IA, Pabinger I, Sofaer S, Hirsh J; American College of Chest Physicians. Venous Thromboembolism,thrombophilia, antithrombotic therapy and pregnancy: American College of Chest Physicians Evidence-Based Clinical Preactice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):844S-886S.    </font></p>      <p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a href="#4-10.">10</a>. Lussana F, Dentali F, Abbate R, d&rsquo;Aloja E, D&rsquo;Angelo A, De Stefano V, Faioni EM, Grandone E, Legnani C, Martinelli I, Simioni P, Tormene D; Italian Society for Haemostasis and Thrombosis. Screening for thrombophilia and antithrombotic prophylaxis in pregnancy: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET). Thromb Res 2009 Nov;124(5):e19-25.</font></p>      <!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana" size="2"> <a name="11"></a></font> <font style="font-size: 10pt;" size="1" face="Verdana" color="#000000"><span lang="en-US"><a href="#11.">11</a>. Otero AM, Pou R, Pons JE, <i>Lens D; De Lisa E, Dellepiane M, Storch E, Attarian D, Ferrari A, Pierri S, Motta N. </i>Trombofilia y p&eacute;rdida recurrente de embarazo. Rev Med Urug 2004; 20:106-113.    </span></font></p>      <!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a href="#12.">12</a>. Robertson L, Wu O, Langhorne P, Twaddle S, Clark P, Lowe GD, Walker ID, Greaves M, Brenkel I, Regan L, Greer IA; Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thrombophilia and pregnancy: a systematic review. Brit J Haematol 2006; 132(2): 171-196.    </font></p>      <!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a href="#13-16.">13</a>. Middledorp S. Thrombophilia and pregnancy complciactions: cause or association? J Thromb Haemost. 2007 Jul; 5( Suppl 1):276-82.     </font> </p>      <!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a href="#13-16.">14</a>. Rodger MA, Paidas M, McLintock C, Middeldorp S, Kahn S, Martinelli I, Hague W, Rosene Montella K, Greer I. Inherites thrombophilia and pregnancy complications revisited. Obstet Gynecol 2008; 112(2 Part 1): 320-24.     </font> </p>      <!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a href="#13-16.">15</a>. Sarig G, Vidergor G, Brenner B. Assessment and management of high-risk pregnancies in women with thrombophilia. Blood Rev 2009; 23(4):143-147.    </font></p>      <!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a href="#13-16.">16</a>. Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D, Machin S, Mackie I, Makris M, Nokes T, Perry D, Tait RC, Walker I, Watson H; British Committee for Standards in Haematology. Clinical Guidelines for testing for heritable thrombophilia. Br J Haematol 2010 Apr;149(2):209-20.     </font> </p>      <!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a href="#17.">17</a>. Otero AM, Sarto A, Amigo MC, Mijares M, Amante de Guggiari P, De Lisa E, Chumpitaz Gloria, Meschengieser S. Trombofilia y embarazo: consenso del Grupo CLAHT. Arch Med Interna (Montevideo);30(2/3):59-63, set. 2008.    </font></p>      <!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a href="#18.">18</a>. Middledorp S. Antithrombotic prophylaxis for women with thrombophilia and pregnancy complications- No. J Thromb Haemost 2003;1(10): 2073-4</font><!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a href="#19.">19</a>. Brenner B. Antithrombotic prophylaxis for women with thrombophilia and pregnancy complications--Yes. J Thromb Haemost 2003;1(10): 2070-2</font><!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a href="#20.">20</a>. Brenner B. Thrombophilia and adverse pregnancy outcome. Obstet Gynecol Clin North Am 2006 Sep;33(3):443-56.    </font></p>      <!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a href="#21.">21</a>. Gris JC, Mercier E, Qu&eacute;r&eacute; I, Lavigne-Lissalde G, Cochery-Nouvellon E, Hoffet M, Ripart-Neveu S, Tailland ML, Dauzat M, Mar&egrave;s P. Low-molecular-weight-heparin versus low-dose aspirin in women with one fetal loss and a constitutional thrombophilic disorder. Blood 2004; 103(10):3695-3699.    </font></p>      <!-- ref --><p style="margin-left: 0.6cm; text-indent: -0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="en-US"> <font style="font-size: 10pt;" size="1" face="Verdana"><a href="#22.">22</a>. Kaandorp S, Di Nisio M et al. Aspirin or anticoagulants for treating recurrent miscarriage in women without antiphospholipid syndrome. Cochrane Database of Systematic Reviews, Issue 1, 2010.     </font> </p>      <p style="text-indent: 0.6cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana" size="2">     <br>  </font>  </p>      <p style="border-style: solid none none; border-color: rgb(0, 0, 0) -moz-use-text-color -moz-use-text-color; border-width: 1px medium medium; padding: 0.18cm 0cm 0cm; margin-bottom: 0cm; line-height: 120%; widows: 0; orphans: 0;" align="justify" lang="es-ES"> <font face="Verdana" size="2">     ]]></body>
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