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Acquired hemophilia A is a rare but severe autoimmune bleeding disorder. It is more frequent in the elderly and results from the presence of autoantibodies directed against clotting factor VIII. In this review, we briefly report on the present state of knowledge regarding acquired hemophilia A, analyzing its epidemiology, pathogenesis, diagnostic, and clinical features. We also describe the main characteristics of this disorder according to its association with different conditions and the most important advances in the treatment of bleeding episodes and the eradication of the autoantibody. Am.

Acquired hemophilia A is a rare bleeding diathesis caused by autoantibodies directed against clotting factor VIII and associated with an increased morbidity and mortality. This autoimmune disorder most commonly occurs in the elderly. Although it may be associated with several underlying pathologies, up to 50% of reported cases remain idiopathic. In contrast with congenital hemophilia, which is commonly characterized by hemarthroses, hemorrhages in patients with acquired hemophilia involve most frequently soft tissues. The 2 treatment priorities are to arrest the acute bleeding and to eradicate the factor VIII autoantibody. Acute bleeding episodes in patients with low-titer inhibitors can be treated using human factor VIII concentrates, whereas factor VIII bypassing agents, such as activated prothrombin complex concentrates or recombinant activated factor VII, are effective for the treatment of those with hightiter inhibitors. An analysis of the literature shows that the most effective first-line treatment for the eradication of factor VIII autoantibodies is the combination of steroids and cyclophosphamide. However, there is increasing evidence on the effectiveness of other treatment approaches, such as immune tolerance regimens and rituximab. If confirmed by large controlled studies, these innovative therapies might become a valid option for long-term eradication of factor VIII inhibitors. (Blood. 2008;112:250-255)

The occurrence of an inhibitor against coagulation factor V (FV) is a rare but challenging condition, which may span from asymptomatic laboratory abnormalities to potentially life-threatening bleeding. The onset of FV inhibitors has been associated most frequently in the past with the patients' exposure to topical bovine thrombin administered during surgery procedures. However, since this preparation is no longer used, in this systematic review we have only focused on non-bovine thrombin-related FV inhibitor cases.

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Over the past forty years the availability of coagulation factor replacement therapy has greatly contributed to the improved care of people with hemophilia. Following the blood-borne viral infections in the late 1970s and early 1980, caused by coagulation factor concentrates manufactured using non-virally inactivated pooled plasma, the need for safer treatment became crucial to the hemophilia community. The introduction of virus inactivated plasma-derived coagulation factors and then of recombinant products has revolutionized the care of these people. These therapeutic weapons have improved their quality of life and that of their families and permitted home treatment, i.e., factor replacement therapy at regular intervals in order to prevent both bleeding and the resultant joint damage (i.e. primary prophylaxis). Accordingly, a near normal lifestyle and life-expectancy have been achieved. The main current problem in hemophilia is the onset of alloantibodies inactivating the infused coagulation factor, even though immune tolerance regimens based on long-term daily injections of large dosages of coagulation factors are able to eradicate inhibitors in approximately two-thirds of affected patients. In addition availability of products that bypass the intrinsic coagulation defects have dramatically improved the management of this complication. The major challenges of current treatment regimens, such the short half life of hemophilia therapeutics with need for frequent intravenous injections, encourage the current efforts to produce coagulation factors with more prolonged bioavailability. Finally, intensive research is devoted to gene transfer therapy, the only way to ultimately obtain cure in hemophilia.

Although a number of studies have demonstrated the influence of ABO blood group on plasma levels of von Willebrand factor (VWF), the nature of this association and its clinical importance is still largely unknown.In this review, the most recent advances in our understanding of the mechanisms by which ABO blood group determines plasma VWF levels and their clinical impact will be discussed.

It is well known that the ABO blood group exerts a major influence on hemostasis, as O blood group individuals have lower von Willebrand factor and factor VIII levels than non-O blood group subjects. To evaluate the possible clinical implication of the different ABO blood groups on the risk of developing venous thromboembolism (VTE), we conducted a meta-analysis of the existing literature. After an electronic search strategy using Medline and Embase and a manual review of abstract books of the International Society on Thrombosis and Haemostasis and of reference lists of all retrieved articles, we included in the systematic review 38 studies with 10,305 VTE cases. The prevalence of non-O blood group was significantly higher in VTE patients compared with controls with a resulting pooled odds ratio (OR) of 2.09 (95% confidence interval [CI], 1.83, 2.38; p < 0.00001). Similar findings were obtained when the genotypes A1O/BO/A2B (OR 1.73, 95% CI, 1.47, 2.05; p < 0.00001) and A1B/A1A1/BB (OR 1.87, 95% CI, 1.84, 2.44; p < 0.00001) were analyzed. The maximum VTE risk was observed in non-O-factor V Leiden patients (OR 7.60, 95% CI, 3.21, 17.99), while for G20210A prothrombin mutation it was not possible to perform a pooled analysis due to a paucity of published studies. Finally, the association between non-O blood group and VTE was weaker when provoked VTE cases were considered (OR 1.33, 95% CI, 1.18, 1.50), while it was substantially unchanged when unprovoked VTE cases were analyzed (OR 1.88, 95% CI, 1.42, 2.50). In conclusion, considering its prevalence, non-O blood group is a candidate to be one of the most important genetic risk factors for venous thrombosis.