<?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>0535-5133</journal-id>
<journal-title><![CDATA[Investigación Clínica]]></journal-title>
<abbrev-journal-title><![CDATA[Invest. clín]]></abbrev-journal-title>
<issn>0535-5133</issn>
<publisher>
<publisher-name><![CDATA[Instituto de Investigaciones Clínicas "Dr. Américo Negrette", Facultad de Medicina, Universidad del Zulia]]></publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id>S0535-51332021000100073</article-id>
<article-id pub-id-type="doi">10.22209/ic.v62n1a07</article-id>
<title-group>
<article-title xml:lang="es"><![CDATA[Tratamiento moderno de la hemofilia y el desarrollo de terapias innovadoras.]]></article-title>
<article-title xml:lang="en"><![CDATA[Modern treatment of hemophilia and development of innovatives therapies.]]></article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname><![CDATA[Ruiz-Sáez]]></surname>
<given-names><![CDATA[Arlette]]></given-names>
</name>
<xref ref-type="aff" rid="Aff"/>
</contrib>
</contrib-group>
<aff id="Af1">
<institution><![CDATA[,Centro Nacional de Hemofilia Departamento de Investigación y Docencia Banco Municipal de Sangre]]></institution>
<addr-line><![CDATA[Caracas ]]></addr-line>
<country>Venezuela</country>
</aff>
<pub-date pub-type="pub">
<day>31</day>
<month>03</month>
<year>2021</year>
</pub-date>
<pub-date pub-type="epub">
<day>31</day>
<month>03</month>
<year>2021</year>
</pub-date>
<volume>62</volume>
<numero>1</numero>
<fpage>73</fpage>
<lpage>95</lpage>
<copyright-statement/>
<copyright-year/>
<self-uri xlink:href="http://ve.scielo.org/scielo.php?script=sci_arttext&amp;pid=S0535-51332021000100073&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://ve.scielo.org/scielo.php?script=sci_abstract&amp;pid=S0535-51332021000100073&amp;lng=en&amp;nrm=iso"></self-uri><self-uri xlink:href="http://ve.scielo.org/scielo.php?script=sci_pdf&amp;pid=S0535-51332021000100073&amp;lng=en&amp;nrm=iso"></self-uri><abstract abstract-type="short" xml:lang="es"><p><![CDATA[Resumen La hemofilia es una enfermedad hemorrágica resultante de mutaciones en el gen del factor VIII (F8) de la coagulación en el caso de la hemofilia A o en el gen del factor IX (F9) en el caso de la hemofilia B, siendo ambas formas indistinguibles clínicamente. El fenotipo clínico usualmente refleja la actividad del factor en plasma y la principal complicación del tratamiento es el desarrollo de aloanticuerpos neutralizantes. El tratamiento moderno de la hemofilia comienza a despuntarse en la década de 1970 con la disponibilidad de concentrados de factores de la coagulación de origen plasmático, el inicio de programas de profilaxis y el manejo multidisciplinario de la condición. Posteriormente, la producción de concentrados seguros, debidamente inactivados o de origen recombinante, facilitó la individualización de la terapia y el desarrollo de los agentes baipás mejoró el tratamiento de pacientes con inhibidores. Para todas esas opciones, la gran limitante ha sido la necesidad de frecuentes infusiones endovenosas por un tiempo indefinido. La biotecnología ha permitido el desarrollo de concentrados de factor VIII y IX de vida media plasmática extendida y a la producción de terapias novedosas, diferentes a la terapia de remplazo, que mejoran la coagulación o inhiben las vías anticoagulantes naturales. Por último, los progresos en la terapia génica como potencial cura de la condición generan grandes expectativas. Si bien estos avances ofrecen alternativas terapéuticas para pacientes con o sin inhibidores, aún están por definirse aspectos relacionados a sus indicaciones, monitorización y seguridad a corto y largo plazo.]]></p></abstract>
<abstract abstract-type="short" xml:lang="en"><p><![CDATA[Abstract Congenital hemophilia is a bleeding disorder caused by mutations in the F8 or F9 clotting factor genes in hemophilia A or in hemophilia B, respectively. The two types of hemophilia are clinically indistinguishable. The clinical phenotype is usually associated with the residual factor level and the main complication of the treatment is the appearance of neutralizing alloantibodies. The modern management of hemophilia began in the 1970s, with the availability of plasma-derived concentrates of coagulation factors, the implementation of prophylaxis programs and a multidisciplinary comprehensive care approach. Later, the therapeutic production of safer virally inactivated and recombinant coagulation factors, allowed for an individualized approach, and the production of bypass agents improved the management of patients with inhibitors. For all these options, the greatest challenge has been the need of life-long frequent intravenous infusions. Biotechnology has made possible the development of Factor VIII and IX concentrates with an extended half-life, as well as the production of therapies other than replacement therapy. These innovations improve clotting or inhibit the natural anticlotting ways. Finally, advances in gene therapy as a potential cure, are generating great expectations. All these advances have offered therapeutic alternatives for hemophilia patients with and without inhibitors. However, long-term safety and monitoring are important issues to be defined.]]></p></abstract>
<kwd-group>
<kwd lng="es"><![CDATA[hemofilia]]></kwd>
<kwd lng="es"><![CDATA[tratamiento]]></kwd>
<kwd lng="es"><![CDATA[innovaciones]]></kwd>
<kwd lng="es"><![CDATA[terapia génica]]></kwd>
<kwd lng="en"><![CDATA[hemophilia]]></kwd>
<kwd lng="en"><![CDATA[treatment]]></kwd>
<kwd lng="en"><![CDATA[innovations]]></kwd>
<kwd lng="en"><![CDATA[gene therapy]]></kwd>
</kwd-group>
</article-meta>
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