RESUMO
Direct oral anticoagulants (DOACs) are small molecule inhibitors of the coagulation proteases thrombin and factor Xa that demonstrate comparable efficacy to warfarin for several common indications, while causing less serious bleeding. However, because their targets are required for the normal host-response to bleeding (hemostasis), DOACs are associated with therapy-induced bleeding that limits their use in certain patient populations and clinical situations. The plasma contact factors (factor XII, factor XI, and prekallikrein) initiate blood coagulation in the activated partial thromboplastin time assay. While serving limited roles in hemostasis, pre-clinical and epidemiologic data indicate that these proteins contribute to pathologic coagulation. It is anticipated that drugs targeting the contact factors will reduce risk of thrombosis with minimal impact on hemostasis. Here, we discuss the biochemistry of contact activation, the contributions of contact factors in thrombosis, and novel antithrombotic agents targeting contact factors that are undergoing pre-clinical and early clinical testing.
Assuntos
Fatores de Coagulação Sanguínea/metabolismo , Coagulação Sanguínea , Animais , Fatores de Coagulação Sanguínea/genética , Transtornos de Proteínas de Coagulação/diagnóstico , Transtornos de Proteínas de Coagulação/epidemiologia , Transtornos de Proteínas de Coagulação/etiologia , Transtornos de Proteínas de Coagulação/terapia , Terapia Combinada , Avaliação Pré-Clínica de Medicamentos , Hemostasia , Humanos , Terapia de Alvo Molecular , Ligação Proteica , Trombina/metabolismoRESUMO
BACKGROUND: Combined deficiency of vitamin K-dependent coagulation factors (II, VII, IX, X) is an uncommon challenge for the expectant gravida. CASE: A 34-year-old primigravida had congenital combined deficiency of factors II, VII, IX, and X that were incompletely sensitive to vitamin K. She had an altered form of vitamin K-dependent factors that retained immunologic activity but lacked coagulant activity and the normal complement of gamma-carboxyglutamic acid residues. She required vitamin K supplementation throughout her life. After an uneventful pregnancy she had postpartum hemorrhage resulting from an episiotomy. Fresh frozen plasma was administered to achieve hemostasis. The remainder of her postpartum course was normal. CONCLUSION: Combined congenital deficiency of factors II, VII, IX, and X can be managed in pregnancy with the use of vitamin K and fresh frozen plasma.