1,721,763 research outputs found
Carrier detection and prenatal diagnosis of hemophilia in developing countries
No full textHemophilia A and B, inherited as X-linked recessive traits, are the most common hereditary hemorrhagic disorders caused by a deficiency or dysfunction of coagulation factor VIII (FVIII) or FIX, respectively. Hemophilia is prevalent worldwide, without ethnic or geographic limitations, and remains a life-threatening and often disabling condition. Advances in molecular medicine in this century have markedly improved hemophilia treatment. However, management is still largely inadequate in developing countries. Therefore, carrier detection and prenatal diagnosis remain the key steps for the prevention of the birth of children with hemophilia in developing countries where patients with this coagulation disorder rarely live beyond childhood. Carrier detection and prenatal diagnosis are possible by direct or indirect genetic analysis of the F8 or F9 genes. In countries with more advanced molecular facilities and higher budget resources, the most appropriate choice in general is a direct strategy for mutation detection by prescreening techniques or direct mutation detection. However, in countries with limited facilities and low budget resources, carrier detection and prenatal diagnosis are usually performed by linkage analysis with genetic markers. This article suggests the possibilities of genetic diagnosis and a feasible strategy for carrier detection and prenatal diagnosis in families with hemophilia A and B in developing countrie
Results of an international, multicentre pharmacokinetic trial in congenital fibrinogen deficiency
No full textRare bleeding disorders represent 3–5% of all inherited coagulation factor disorders. Inherited afibrinogenemia, which is caused by a deficiency in plasma fibrinogen (coagulation factor I), accounts for only a small portion of all the rare bleeding disorders. Patients with afibrinogenemia have a variable bleeding pattern that may include potentially serious or life-threatening haemorrhages. Treatment of afibrinogenemia is aimed at replacing the missing fibrinogen to restore efficient haemostasis and to stop bleeding. Three sources of fibrinogen are currently available: fresh frozen plasma, cryoprecipitate, and lyophilized fibrinogen concentrate. Owing to its rarity, little is known about the optimal treatment of patients with afibrinogenemia, including the pharmacokinetics of fibrinogen concentrate. To explore this further, we conducted a prospective, open-label, uncontrolled, multinational pharmacokinetic trial of pasteurized human fibrinogen concentrate in 15 patients with afibrinogenemia. Infusion of a single dose of fibrinogen concentrate (70 mg/kg body weight) resulted in similar fibrinogen antigen and activity levels, which were highly correlated. Fibrinogen levels rose rapidly following infusion to reach a maximum of approximately 1.3 g/L at 1 hour. Fibrinogen concentrate effectively restored clot formation, based on the surrogate thromboelastographic end-point of maximum clot firmness. The concentrate was well tolerated and there were no treatment-related adverse events or evidence of viral transmission during the study
Epidemiology and treatment of congenital fibrinogen deficiency
No full textCongenital fibrinogen deficiency is a rare bleeding disorder, affecting either the quantity (afibrinogenemia, hypofibrinogenemia) or quality (dysfibrinogenemia) of circulating fibrinogen. There is a strong association between fibrinogen activity levels and clinical bleeding severity. Patients with afibrinogenemia experience frequent, often severe, spontaneous bleeds into the muscles and joints and are at significant risk of intracranial hemorrhage. Patients with hypofibrinogenemia are usually asymptomatic; however, they are vulnerable to bleeding after trauma. Dysfibrinogenemia is associated with both spontaneous bleeding and a relatively high risk of thrombosis. Fibrinogen replacement therapy is effective in treating bleeding episodes in congenital fibrinogen deficiency. Fibrinogen concentrates are the preferred treatment option and guidelines now exist for their on-demand use and to manage surgery. Prophylaxis may benefit patients with afibrinogenemia and others with a severe bleeding tendency. The dose and frequency of administration should be adjusted to maintain a fibrinogen activity level >0.5-1.0 g/L. Pregnant women with afibrinogenemia require prophylactic factor replacement as early as possible during pregnancy, continuing throughout pregnancy, and after the birth. Fibrinogen replacement should also be considered in pregnant women with other fibrinogen deficiencies. The risk of thrombosis presents an additional management challenge in these patients, often necessitating the concurrent use of anticoagulants and fibrinogen. Although basic guidelines have been developed, further studies are needed to help optimize treatment in different patient groups under different clinical circumstances and to improve our understanding of thrombotic event
TTP and ADAMTS13 : When Is Testing Appropriate?
No full textThe last 10 years witnessed the publication of many studies on the pathophysiology of thrombotic thrombocytopenic purpura (TTP), a life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and multiorgan failure. The most important finding was the identification of a novel metalloprotease, named ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motives), that is involved in the regulation of the size of von Willebrand factor (VWF), a major modulator of platelet adhesion and aggregation in the microcirculation. Inherited or acquired deficiencies of ADAMTS13 impair VWF cleavage, leading in turn to the disseminated formation of platelet-rich thrombi in the micro-circulation and to symptoms of end-organ ischemia. By measuring ADAMTS13 in plasma, it has been clearly shown that patients with inherited TTP have severe ADAMTS13 deficiency. However, patients with acquired TTP present with clinical and laboratory heterogeneity, and there are unequivocal cases of acquired TTP with measurable plasma levels of ADAMTS13. This heterogeneity poses a challenge for understanding the pathogenesis of TTP and selecting appropriate therapies
Rare coagulation disorders
No full textThe type of hemorrhagic manifestations that occur in patients with recessively transmitted coagulation disorders and their optimal treatment are not well established as for hemophilia A and B and von Willebrand disease, due to the rarity of these disorders. In a Muslim country like Iran where consanguineous marriages are frequent these disorders are less rare. We chose to evaluate the pattern of bleeding symptoms in 237 Iranian patients with the inherited deficiencies of fibrinogen, factor II, combined factor V and factor Vm, factor V, factor Vn and factor X. Considering "severe" life-endangering hemorrhages such as those in the CNS, gastrointestinal tract and from the umbilical cord and those potentially handicapping such as hematomas and hemarthroses; and "mild" epistaxis, menorrhagia, hematuria, oral and postsurgical bleeding, it would appear the most severe diseases are factor X and factor II deficiencies. For the remaining defects only a minority of patients, even those with unmeasurable plasma levels, had life-endangering hemorrhages or muscoloskeletal disabilities as a consequence of hemarthroses and hematomas. The relatively mild severity of clinical manifestations in recessive coagulation disorders commands safety as the primary criterion in the choice of replacement material for treatment. Hence, virally inactivated plasma and factor concentrates should be the products of choice
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