Haemophilia : the official journal of the World Federation of Hemophilia
-
Inherited deficiencies of plasma proteins involved in blood coagulation generally lead to lifelong bleeding disorders. The severity of these disorders is generally inversely proportional to the degree of factor deficiency. Among all the autosomal recessive rare bleeding disorders, which include afibrinogenaemia, factor (F) II, FV, FV + VIII, FVII, FX, FXI, FXIII, the combined deficiency of coagulation FV and FVIII (F5F8D or FV + FVIII) is exceptional because it is due to mutations in genes encoding proteins involved in the FV and FVIII intracellular transport (LMAN1 and MCFD2) rather than DNA defects in the genes that encode the corresponding coagulation factors. ⋯ F5F8D is characterized by concomitantly low levels (usually between 5% and 20%) of both FV and FVIII, and is associated with a mild to moderate bleeding tendency. Treatment of bleeding episodes requires a source of both FV and FVIII; replacement of FV is achieved through the use of fresh frozen plasma, and that of FVIII by desmopressin or specific FVIII concentrates, plasma-derived or recombinant FVIII products. We focus here on the clinical, molecular, treatment-related and diagnostic features of F5F8D.
-
Fibrinogen, a hexameric glycoprotein encoded by three genes - FGA, FGB, FGG - clustered on chromosome 4q is involved in the final steps of coagulation as a precursor of fibrin monomers required for the formation of the haemostatic plug. Inherited disorders of fibrinogen abnormalities are rare and not as well clinically characterized as some other inherited bleeding disorders. To characterize the clinical manifestations, molecular defects and treatment modalities of these rare disorders, a Medline search from January 1966 to September 2007 for these disorders reported in large studies and registries was undertaken. ⋯ Use of some of these products carries risks of viral transmission, antibody development and thromboembolic events. Establishment of registries in Iran, Italy and North America has fostered a better understanding of these disorders with an attempt to explore molecular defects. Rare Bleeding Disorder Registries developed through the United States and international efforts hopefully will encourage development and licensure of safer, effective products.
-
Hereditary haemorrhagic telangiectasia (also known as Osler-Weber-Rendu syndrome) is a relatively common, under-recognized autosomal-dominant disorder that results from multisystem vascular dysplasia. It is characterized by telangiectases and arteriovenous malformations of skin, mucosa and viscera. This article summarizes the clinical manifestations and the management of this disorder and its management. This review underscores an urgent need to conduct prospective multicentre studies to develop evidence-based management guidelines for this disease.
-
Inherited factor XIII (FXIII) deficiency is a rare bleeding disorder that can present with umbilical bleeding during the neonatal period, delayed soft tissue bruising, mucosal bleeding and life-threatening intracranial haemorrhage. FXIII deficiency has also been associated with poor wound healing and recurrent miscarriages. FXIII plays an integral role in haemostasis by catalysing the cross-linking of fibrin, platelet membrane and matrix proteins throughout thrombus formation, thus stabilizing the blood clot. ⋯ There have been more than 60 FXIII mutations identified in the current literature. In addition, single nucleotide polymorphisms have been described, some of which have been shown to affect FXIII activity, contributing further to the heterogeneity in patient presentation and severity of clinical symptoms. Although there is a lifelong risk of bleeding, the prognosis is excellent when current prophylactic treatment is available using cryoprecipitate or plasma-derived FXIII concentrate.
-
Historical Article
Haemate P von Willebrand factor/factor VIII concentrate: 25 years of clinical experience.
Although von Willebrand disease (VWD) has a very long history, our understanding and treatment of the bleeding disorder has only evolved during the past 50 years or so. It was not until the 1920s that VWD was first recognized as a disease separate from that of classical haemophilia. It then took another 30 years before the first effective treatment was developed. ⋯ One of the key milestones in the evolution of the treatment of VWD was the development of Haemate P/Humate-P (CSL Behring) - the first virus-inactivated factor VIII plasma product. For 25 years, this concentrate has demonstrated excellent clinical efficacy and safety for patients with VWD and for those with haemophilia. This article provides an historical overview of the early landmark efforts to ensure a safe plasma-derived replacement product and outlines the clinical evolution in the use of Haemate P.