<?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>0120-5633</journal-id>
<journal-title><![CDATA[Revista Colombiana de Cardiología]]></journal-title>
<abbrev-journal-title><![CDATA[Rev. Colomb. Cardiol.]]></abbrev-journal-title>
<issn>0120-5633</issn>
<publisher>
<publisher-name><![CDATA[Sociedad Colombiana de Cardiologia. Oficina de Publicaciones]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0120-56332022000100100</article-id>
<article-id pub-id-type="doi">10.24875/rccar.m22000124</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Estudios genéticos del metabolismo de la warfarina y su utilidad en la toma de decisiones]]></article-title>
<article-title xml:lang="en"><![CDATA[Genetic studies of warfarin metabolism and its usefulness in decision making]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ramírez-Ramos]]></surname>
<given-names><![CDATA[Cristhian F.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Castilla-Agudelo]]></surname>
<given-names><![CDATA[Gustavo A.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Corrales-Gómez]]></surname>
<given-names><![CDATA[Jacobo]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Martínez-Cano]]></surname>
<given-names><![CDATA[Carlos A.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Saldarriaga-Giraldo]]></surname>
<given-names><![CDATA[Clara I.]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
<xref ref-type="aff" rid="Aaf"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Universidad Pontífica Bolicariana Departamento de Cardiología Intervencionista y Hemodinámica ]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af2">
<institution><![CDATA[,Clínica CardioVID  ]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af3">
<institution><![CDATA[,Universidad Pontifica Bolivariana Departamento de Cardiología Clínica ]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af4">
<institution><![CDATA[,Universidad de Antioqui Departamento de Anestesiología ]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<aff id="Af5">
<institution><![CDATA[,Departamento de Cardiología  ]]></institution>
<addr-line><![CDATA[Medellín ]]></addr-line>
<country>Colombia</country>
</aff>
<pub-date pub-type="pub">
<day>00</day>
<month>02</month>
<year>2022</year>
</pub-date>
<pub-date pub-type="epub">
<day>00</day>
<month>02</month>
<year>2022</year>
</pub-date>
<volume>29</volume>
<numero>1</numero>
<fpage>100</fpage>
<lpage>105</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_arttext&amp;pid=S0120-56332022000100100&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_abstract&amp;pid=S0120-56332022000100100&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://www.scielo.org.co/scielo.php?script=sci_pdf&amp;pid=S0120-56332022000100100&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen  Introducción: Al momento de valorar la necesidad de realizar un reemplazo quirúrgico valvular cardiaco es posible elegir entre una válvula mecánica o una bioprotésica; la elección debe tener presentes los riesgos de la terapia anticoagulante y la necesidad potencial o el riesgo de nuevas intervenciones. La anticoagulación se realiza con antagonistas de la vitamina K, y de estos, la warfarina es el que se prescribe con mayor frecuencia. Por su metabolismo hepático (P450), dicho medicamento tiene múltiples interacciones farmacológicas y no farmacológicas que en ocasiones se convierten en un verdadero problema en la práctica clínica. Hasta la fecha no se recomienda realizar de forma rutinaria una dosificación guiada por genotipo; sin embargo, se requieren estudios genéticos para definir conductas médicas cuando se hace difícil su manejo.  Caso clínico: Se describe el caso de una mujer de 37 años portadora de una válvula mitral mecánica por enfermedad reumática, anticoagulada de forma crónica con warfarina; sin embargo, durante el seguimiento tuvo múltiples consultas a urgencias (entre dos y tres veces por mes) por niveles de anticoagulación en rangos subterapéuticos, como valores elevados de INR. Presentó infarto agudo de miocardio con coronarias sanas e isquemia cerebral transitoria en contexto de INR bajo, considerados así de etiología tromboembólica. Por estas dificultades se decidió realizar la medición de los niveles de factor II de la coagulación, el cual fue normal a pesar del uso del medicamento, por lo que se sospechó resistencia al fármaco. Se solicitó estudio genético que mostró genotipo asociado con actividad enzimática reducida o normal de la CYP2C9, además un genotipo WARF CYP2C9 *1/*2 y WARF VKORC1 A/A, con lo cual se concluyó que la paciente presentaba un comportamiento metabólico divergente para warfarina. Se decidió realizar un reemplazo de válvula mecánica por válvula bioprotésica, con el objetivo de suspender el uso de la warfarina. La paciente presentó una evolución clínica satisfactoria.  Conclusiones: La farmacogenética ha logrado identificar polimorfismos en los genes implicados en el metabolismo de la warfarina, los cuales están relacionados con riesgo de sangrado. Estas variantes se encuentran relacionadas con los genes CYP2C9, CYP4F2 y VKORC1. Si bien no se ha demostrado un impacto clínico en los ajustes de warfarina guiados por genotipo, dichos exámenes se hacen necesarios en algunos casos para sugerir un cambio en la dosis del medicamento o su suspensión definitiva.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract  Introduction: When assessing the need for a cardiac valvular surgical replacement, it is possible to choose between a mechanical or bioprosthetic valve; The choice must take into account the risks of anticoagulant therapy and the potential need and/or risk of new interventions. Anticoagulation is performed with vitamin K antagonists and warfarin is the most commonly prescribed of these. This medicine due to its hepatic metabolism (P450) has multiple pharmacological and non-pharmacological interactions that sometimes become a real problem in clinical practice. To date, it is not recommended to routinely perform a genotype-guided dosage. However, such genetic studies are necessary to define medical behaviors when handling is difficult.  Case report: It is described a case of a 37-year-old woman with a mechanical mitral valve due to rheumatic disease, chronically anticoagulated with warfarin; however, during the follow-up with multiple emergency consultations (2-3 times per month) for anticoagulation levels in subtherapeutic ranges such as elevated INR levels. She presented acute myocardial infarction with healthy coronary arteries and transient cerebral ischemia in the context of low INR thus considered thromboembolic etiology. Due to these difficulties, it was decided to measure coagulation factor II levels, which was normal despite the use of the drug, suspecting drug resistance. A genetic study was requested that showed genotype associated with reduced or normal CYP2C9 enzymatic activity, plus a WARF CYP2C9 * 1/* 2 and WARF VKORC1 A/A genotype concluding that the patient presented a divergent metabolic behavior for warfarin. It was decided to perform a mechanical valve replacement with a bioprosthetic valve, in order to suspend the use of warfarin. The patient presented a satisfactory clinical evolution.  Conclusions: Pharmacogenetics has managed to identify polymorphisms in the genes involved in warfarin metabolism, which are related to bleeding risk. These variants are related to the CYP2C9, CYP4F2 and VKORC1 genes. Although no clinical impact has been demonstrated in genotype-guided warfarin adjustments, such tests are necessary in some cases to suggest a change in the dose of the medication or the definitive suspension.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[Polimorfismo genético]]></kwd>
<kwd lng="es"><![CDATA[Warfarina]]></kwd>
<kwd lng="es"><![CDATA[Anticoagulantes]]></kwd>
<kwd lng="es"><![CDATA[Válvula mitral]]></kwd>
<kwd lng="en"><![CDATA[Genetic polymorphism]]></kwd>
<kwd lng="en"><![CDATA[Warfarin]]></kwd>
<kwd lng="en"><![CDATA[Anticoagulants]]></kwd>
<kwd lng="en"><![CDATA[Mitral valve]]></kwd>
</kwd-group>
</article-meta>
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