RESUMO
The main treatment option for Hemophilia A/B patients involves the administration of recombinant coagulation factors on-demand or in a prophylactic approach. Despite the safety and efficacy of this replacement therapy, the development of antibodies against the coagulation factor infused, which neutralize the procoagulant activity, is a severe complication. The production of recombinant coagulation factors in human cell lines is an efficient approach to avoid such complication. Human cell lines can produce recombinant proteins with post translation modifications more similar to their natural counterpart, reducing potential immunogenic reactions. This review provides a brief overview of the most important characteristics of recombinant FVIII and FIX products available on the market and the improvements that have recently been achieved by the production using human cell lines.
Assuntos
Fator IX/biossíntese , Fator IX/genética , Fator VIII/biossíntese , Fator VIII/genética , Melhoramento Genético/métodos , Engenharia de Proteínas/métodos , Animais , Fatores de Coagulação Sanguínea/biossíntese , Fatores de Coagulação Sanguínea/genética , Células COS , Clonagem Molecular/métodos , Células HEK293 , Células Hep G2 , Humanos , Conformação Proteica , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Especificidade da EspécieRESUMO
The liver plays a central role in the clotting process. In this organ are sintetizated the major part of the coagulation factors. Historically, was considered that alteration in liver function causes important bleeding disorders. However, actual evidence is not in agreement with this asseveration. Decreased synthesis of clotting and inhibitor factors, decrease clearance of activated factors, quantitative and qualitative platelet defects, hyperfibrinolysis and intravascular coagulation are some of the defects observed in liver diseases. Thrombotic events, even if rare in cirrhotic patients, occur manly in the portal and mesenteric veins. The aim of the present work is to review the present evidence in coagulation disorders and liver disease.
Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Cirrose Hepática/complicações , Afibrinogenemia/etiologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Fatores de Coagulação Sanguínea/biossíntese , Plaquetas/fisiologia , Coagulação Intravascular Disseminada/etiologia , Coagulação Intravascular Disseminada/fisiopatologia , Fibrinólise , Transtornos Hemorrágicos/etiologia , Transtornos Hemorrágicos/fisiopatologia , Humanos , Cirrose Hepática/fisiopatologia , Veias Mesentéricas , Veia Porta , Trombofilia/etiologia , Trombofilia/fisiopatologia , Trombopoetina/biossíntese , Trombopoetina/deficiência , Trombose/etiologia , Deficiência de Vitamina K/etiologiaRESUMO
The liver plays a central role in the clotting process. In this organ are sintetizated the major part of the coagulation factors. Historically, was considered that alteration in liver function causes important bleeding disorders. However, actual evidence is not in agreement with this asseveration. Decreased synthesis of clotting and inhibitor factors, decrease clearance of activated factors, quantitative and qualitative platelet defects, hyperfibrinolysis and intravascular coagulation are some of the defects observed in liver diseases. Thrombotic events, even if rare in cirrhotic patients, occur manly in the portal and mesenteric veins. The aim of the present work is to review the present evidence in coagulation disorders and liver disease.
El hígado participa de manera importante en el proceso de la coagulación. En él se sintetizan la mayor parte de los factores pro- y anticoagulantes. De manera histórica se ha considerado que las alteraciones en la función de este órgano provoca trastornos predisponentes para eventos de sangrado. La evidencia actual pone en tela de juicio esta aseveración. En los casos de hepatopatía se hacen evidentes alteraciones en el número y funcionamiento de las plaquetas, disminución de la síntesis de factores de la coagulación, disfibrinogenemia, alteraciones en la fibrinólisis, deficiencia de vitamina K y cambios similares a los ocurridos en la coagulación intravascular diseminada (CID). El presente trabajo está dirigido a revisar los conocimientos actuales respecto a las alteraciones de la coagulación presentes en los pacientes con hepatopatías.