A Case of Central Retinal Vein Occlusion by Protein C Deficiency / 임상소아혈액종양

Protein C (PC) is a vitamin K-dependent plasma protein synthesized as a zymogen by liver. It's active form has an anti-thrombotic activity by cleaving the coagulation factor Va and VIIIa. During the last few years, a large number of cases with protein C deficiency (PCD) which contain variable mutations have been documented. Those with hereditary protein C deficiency tend to have an increased risk of thromboembolism. Hypertension, diabetes, hyperlipidemia and glaucoma are the main underlying diseases of the retinal vein occlusion (RVO). Rarely, thrombophilia (antithrombin III, protein S, protein C deficiency) results in the RVO which usually occurs after adolescent period. We recently experienced a case of central retinal vein occlusion by a PCD.

A Case of Central Retinal Vein Occlusion by Protein C Deficiency / 임상소아혈액종양

Protein C (PC) is a vitamin K-dependent plasma protein synthesized as a zymogen by liver. It's active form has an anti-thrombotic activity by cleaving the coagulation factor Va and VIIIa. During the last few years, a large number of cases with protein C deficiency (PCD) which contain variable mutations have been documented. Those with hereditary protein C deficiency tend to have an increased risk of thromboembolism. Hypertension, diabetes, hyperlipidemia and glaucoma are the main underlying diseases of the retinal vein occlusion (RVO). Rarely, thrombophilia (antithrombin III, protein S, protein C deficiency) results in the RVO which usually occurs after adolescent period. We recently experienced a case of central retinal vein occlusion by a PCD.

The role of autolysis loop in determining the specificity of coagulation proteases

We recently demonstrated that the substitution of the autolysis loop (residues 143 to 154 in the chymotrypsin numbering system) of activated protein C (APC) with the corresponding loop of factor Xa (fXa) renders the APC mutant (APC/fX143-154) susceptible to inhibition by antithrombin (AT) in the presence of pentasaccharide. Our recent results further indicated, that in addition to an improvement in the reactivity of APC/fX143-154 with AT, both the amidolytic and anti-factor Va activities of the mutant APC have also been significantly increased. Since the autolysis loop of APC is five residues longer than the autolysis loop of fXa, it could not be ascertained whether this loop in the mutant APC specifically interacts with the activated conformation of AT or if a shorter autolysis loop is responsible for a global improvement in the catalytic activity of the mutant protease. To answer this question, we prepared another APC mutant in which the autolysis loop of the protease was replaced with the corresponding loop of trypsin (APC/Tryp143-154). Unlike an ~500-fold improvement in the reactivity of APC/fX143-154 with AT in the presence of pentasaccharide, the reactivity of APC/Tryp143-154 with the serpin was improved ~10-fold. These results suggest that both the length and structure of residues of the autolysis loop are critical for the specificity of the coagulation protease interaction with AT. Further factor Va inactivation studies with the APC mutants revealed a similar role for the autolysis loop of APC in the interaction with its natural substrate.

Comparação dos métodos molecular (PCR-RFLP)e coagulométrico para a detecção de fator V Leiden/resistência à proteína C ativada / Comparison of the methods molecular (PCR-RFLP) and coagulométrico for the detention of factor V Leiden/resistance to activated protein C

A proteína C (PC) é um anticoagulante natural, cuja ação consiste em clivar os fatores Va e VIIIa e, desta forma, limita a formação da trombina. O fator V Leiden (F V Leiden) é resultante da mutação G1691A no gene do fator V e leva a resistência à ação da proteína C ativada (rPCA). A detecção de Fator V Leiden é usualmente feita por método molecular, através da reação em cadeia dapolimerase e polimorfismo de restrição (PCR-RFLP). Esta técnica é bastante complexa e não está, ainda, ao alcance dos laboratórios de menor porte. No entanto, a rPCA pode ser avaliada por método coagulométrico, accessível a todos os laboratórios. O objetivo do presenteestudo foi avaliar a eficácia do método coagulométrico para detecção da resistência hereditária à proteína C ativada, comparando-se os resultados obtidos por esse método e pela detecção de Fator V Leiden por PCR-RFLP. Os participantes deste estudo foram selecionadosdentre indivíduos portadores de mutação de importância em trombofilia, porém assintomáticos, pertencentes a famílias de pacientes que já sofreram evento trombótico (portadores de mutações de importância em trombofilia). O primeiro grupo (grupo I) foi composto por não-portadores da mutação G1691A (n=57) e o segundo (grupo II) por portadores da mutação G1691A (no gene do FV)em heterozigose (n=25). O teste molecular foi feito por reação em cadeia da polimerase, seguida da digestão com endonucleases de restrição (PCR-RFLP) e o método coagulométrico, utilizando-se o conjunto diagnósticoCOATEST APC RESISTANCE V da CHROMOGENIX.Os resultados obtidos demonstraram uma grande concordância entre a identificação do FV Leiden por PCR e detecção de rPCA por método coagulométrico utilizando plasma deficiente em FV. Todos os portadores da mutação G1691A (no gene do FV) apresentaram resistência à proteína Cativada e essa resistência não foi observada entre os não-portadores. Esses resultados permitem concluir que o teste coagulométrico com diluição em plasma deficiente em FV,...

Anesthesia for Living Related Liver Transplantation in Homozygous Protein C Deficiency / 대한마취과학회지

Protein C exerts anticoagulant effects by inactivating factor Va and VIIIa and stimulating fibrinolysis. The homozygous protein C deficiency is extremely rare and often results in life threatening thrombosis and purpura fulminans with necrotic cutaneous lesions. A child with homozygous protein C deficiency was treated at 6 months by a living-related liver transplantaion. After induction of anesthesia, we started an FFP infusion for protein C replacement and a low molecular weight heparin continuous infusion to prevent thrombosis. A complete reconstitution of protein C activity and resolution of the thrombotic condition occured postoperatively. So we report this case with a brief review of the literature.

Resistência à proteína C ativada / Resistance to activeted protein C

O fator V da coagulaçäo, quando ativado, participa como um co-fator essencial na ativaçäo da pró-trombina pelo fator X ativado. O fator V ativado é inativado pela proteína C ativada, numa reaçäo potencializada pela proteína S. Uma mutaçäo no éxon 10 (Arg 506 Gln) do gene do fator V dß origem a uma molécula do fator V que näo é adequadamente inativada pela proteína C ativada, o que causa a chamada resistência à proteína C ativada.