1,721,058 research outputs found
Advances in the genetics and treatment of von Willebrand disease
No full textvon Willebrand disease (VWD) is a bleeding disorder caused by quantitative (type 1 and 3) or qualitative (type 2) defects of von Willebrand factor (VWF). The mechanisms of most inherited VWD types have been recently elucidated by genetic and molecular diagnosis, but the phenotypic tests based on measurements of plasma and platelet VWF, the ability of VWF to interact with its platelet receptor, and the analysis of the multimeric composition of VWF are always essential to identify patients with different VWD subtypes. The aim of treatment is to correct the dual defects of hemostasis, ie, abnormal coagulation expressed by low levels of factor VIII (FVIII) and abnormal platelet adhesion expressed by prolonged bleeding time (BT). Desmopressin is the treatment of choice in most patients with type 1 and type 2 VWD, who account for 60 to 70% of cases. In type 3 and in some severe forms of type 1 and type 2 VWD, desmopressin is not effective, and it is necessary to resort to plasma concentrates containing FVIII and VWF. Treated with virucidal methods, these concentrates are effective and currently safe, but they do not always correct the BT defect. Platelet concentrates or desmopressin can be used as adjunctive treatments when poor correction of the BT after concentrates is associated with continued bleeding
ALLOANTIBODIES IN CONGENITAL VONWILLEBRANDS DISEASE
No full textIn a review of the literature published in 1984 we identified (from 13 kindreds) 15 patients with severe von Willebrand's disease (vWD) reported to have developed alloantibodies. In order to reexamine the problem, a questionnaire was sent in 1989 to 141 hemophilia centers in America and Europe; 101 answers were received. These dealt with a total number of 1,720 patients with vWD (all types) and 231 patients with severe (type III) vWD. Besides the 15 cases reported in 1984, 6 additional cases of anti-vWF alloantibodies were reported, i.e., one from Spain (a relative of a previously reported case), two from Venezuela (brother and sister) and three from North Carolina (unrelated patients). All these cases and those previously reported share the following features: occurrence of alloantibodies in multitransfused patients with severe vWD, poor clinical and laboratory- response to replacement therapy with cryoprecipitate, inhibition of ristocetin-induced platelet aggregation. During the survey, an unusual antibody to FVIII:C with no reactivity towards vWF was reported in a multitransfused girl (from Tennessee) with type III vWD. It seems therefore that although the development of alloantibodies is a rare complication of severe vWD, due to its negative effect on the response to treatment it needs a prompt identification
PREDICTIVE VALUE OF COAGULATION TESTS IN ARTERIAL THROMBOSIS
No full textIn five large-scale prospective studies the predictive value of hemostatic parameters indicating the occurrence of arterial thrombotic diseases has been estimated in healthy individuals. All the studies have consistently found a statistically significant association between hyperfibrinogenemia and arterial thrombotic diseases. In two studies, increased levels of factor VII were associated with an increased incidence of ischemic heart disease. The relationship between arterial occlusive diseases and plasma levels of fibrinogen or factor VII was closer than that for other well established risk factors such as plasma cholesterol. These data indicate the important pathogenetic role carried out by alterations of the clotting system in occlusive arterial diseases
The complex differential diagnosis between thrombotic thrombocytopenic purpura and the atypical hemolytic uremic syndrome : laboratory weapons and their impact on treatment choice and monitoring
No full textThrombocytopenia and microangiopathic hemolytic anemia are the hallmark of the thrombotic microangiopathies (TMAs) thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). TTP, inherited or autoimmune, is mainly caused by the plasma deficiency of the von Willebrand factor cleaving protease ADAMTS13, owing to gene mutations or autoantibodies. Typical HUS is often caused by infections with Shiga-Toxin-producing Escherichia coli and thus is called STEC-HUS. The rarer atypical form of HUS is often associated with complement dysregulation, owing to the inherited deficiency or dysfunction of factor H or other complement proteins. In the past the distinction between these TMAs was almost exclusively based on clinical grounds, the term TTP being used for cases with predominant neurological involvement, STEC HUS for cases presenting with bloody diarrhea and atypical HUS identifying patients with severe renal damage. However the clinical presentation may not easily distinguish TTP from atypical HUS. A more accurate differential diagnosis has clinical implications, because plasma exchange (the treatment of choice in TTP) is much less effective in atypical HUS, which shows dramatic short- and long-term therapeutic benefits from eculizumab, a monoclonal antibody that inhibits complement activation. This article will point out that the measurement of ADAMTS13 is able to diagnose accurately the majority of TTP cases, and that very simple tests such as the platelet count and serum creatinine can predict the deficiency of the protease with a good degree of accuracy. In atypical HUS, new methods were recently developed that not only demonstrate the activation of the complement system, i.e., the main disease mechanism, but also help to tailor the short- and long-term treatment with eculizumab
Diagnosis and management of acquired von Willebrand syndrome
No full textThe acquired von Willebrand syndrome is a rare bleeding disorder with laboratory finding similar to those of congenital von Willebrand's disease. Unlike the congenital form, however, the acquired syndrome usually occurs in persons with no personal or family history of bleeding. Large-scale studies are not available, diagnosis is still difficult, and treatment is empirical. Published findings and an international registry indicate that the syndrome is especially frequent in lympho- or myeloproliferative disorders; therefore, it should be suspected when there is excessive bleeding in patients with these disorders. Acquired von Willebrand syndrome is also associated with solid tumors, immunologic and cardiovascular, disorders. Diagnosis is based on assays measuring ristocetin cofactor activity or collagen binding; these levels are usually abnormally low, while factor VIII coagulant activity can be normal. Factor VIII/von Willebrand factor-inhibiting activities are found in only a minority of cases. Bleeding episodes in patients with the syndrome are mostly of the mucocutaneous type and can be managed with desmopressin, plasma-derived factor VIII/von Willebrand factor concentrates, and intravenous immunoglobulin. Recombinant activated factor VII, plasmapheresis, corticosteroids, and immunosuppressors combined with chemotherapy are also useful in some cases. Acquired von Willebrand syndrome, although rare, warrants further understanding for clinical practice
Venocclusive disease of the liver after bone marrow transplantation: The role of hemostasis
No full textPoor relationship between phenotypes of protein S deficiency and mutations in the protein S alpha gene
No full textBy single strand conformational polymorphism, nucleotide sequencing and enzyme restriction, we analyzed the protein S α gene in 17 protein S-deficient probands and in their available family members. The relationship between genotype and phenotype was also evaluated. Twelve different sequence variations were identified in 17 probands. Ten were putative causal mutations distributed in 16 probands: 4 were nonsense, 5 missense and one a splice site mutation. In most families in which a mutation was identified, more than one phenotype of PS deficiency was present. The same splice site mutation (intron j G-A, exon 10 + 5) was associated with type I deficiency in one family and with type I/III in another unrelated family. A phenotypic discrepancy was also observed for the Arg474Pro, Gly597Asp and Arg410stop mutations. Glu26Ala, previously reported in kindreds with type I deficiencies, was found in association with I, II and III phenotypes in four unrelated kindreds. Phenotypic analysis of protein S deficiency is poorly related to the underlying genetic defect
International survey of attitudes towards secondary prophylaxis with recombinant factor VIIa in haemophilia A patients with inhibitors
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