RESUMO
Factor XIII, a heterotetrameric proenzyme, is converted to an activated transglutaminase by thrombin and calcium in the final phases of coagulation. Factor XIII catalyzes the formation of crosslinks between fibrin monomers and between α2-antiplasmin and fibrin. These crosslinks mechanically stabilize fibrin against shear stress, enable red cell retention within the clot, and protect the clot from premature degradation. Congenital factor XIII deficiency is caused by autosomal recessive mutations, presenting early in life with a severe bleeding diathesis. Acquired deficiency may be caused by autoimmunity. Currently available assays for laboratory diagnosis of factor XIII deficiency include clot solubility assays, quantitative factor XIII activity assays, factor XIII antigen assays, and genetic testing. The International Society on Thrombosis and Haemostasis Scientific and Standardization Committee has recommended an algorithm for the laboratory diagnosis and differentiation of the different forms of factor XIII deficiency. However, implementation of this algorithm has been limited by technical and budgetary challenges associated with the currently available factor XIII-specific assays. The purpose of this review is to discuss the advantages and limitations of the currently available assays employed for the laboratory diagnosis of factor XIII deficiency.
Assuntos
Fator XIII/metabolismo , Laboratórios , Antígenos/metabolismo , Testes de Coagulação Sanguínea , Fator XIII/genética , Técnicas de Genotipagem , HumanosAssuntos
Algoritmos , Deficiência do Fator XIII/diagnóstico , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Autoanticorpos/sangue , Autoanticorpos/imunologia , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Plaquetas/química , Consanguinidade , Éxons/genética , Fator XIII/análise , Fator XIII/genética , Fator XIII/imunologia , Deficiência do Fator XIII/classificação , Deficiência do Fator XIII/epidemiologia , Deficiência do Fator XIII/genética , Testes Hematológicos/economia , Humanos , Incidência , Irã (Geográfico)/epidemiologia , Mutação de Sentido Incorreto , Mutação Puntual , Reação em Cadeia da Polimerase/economia , Subunidades Proteicas/genética , SolubilidadeRESUMO
The plasma circulating zymogenic coagulation factor XIII (FXIII) is a protransglutaminase, which upon activation by thrombin and calcium cross-links preformed fibrin clots/fibrinolytic inhibitors making them mechanically stable and less susceptible to fibrinolysis. The zymogenic plasma FXIII molecule is a heterotetramer composed of two catalytic FXIII-A and two protective FXIII-B subunits. Factor XIII deficiency resulting from inherited or acquired causes can result in pathological bleeding episodes. A diverse spectrum of mutations have been reported in the F13A1 and F13B genes which cause inherited severe FXIII deficiency. The inherited severe FXIII deficiency, which is a rare coagulation disorder with a prevalence of 1 in 4 million has been the prime focus of clinical and genetic investigations owing to the severity of the bleeding phenotype associated with it. Recently however, with a growing understanding into the pleiotropic roles of FXIII, the fairly frequent milder form of FXIII deficiency caused by heterozygous mutations has become one of the subjects of investigative research. The acquired form of FXIII deficiency is usually caused by generation of autoantibodies or hyperconsumption in other disease states such as disseminated intravascular coagulation. Here, we update the knowledge about the pathophysiology of factor XIII deficiency and its therapeutic options.