Disease relevance of von Willebrand Disease

• Thus, the deficiencies of VIII:C and VIII/VWF in hemophilia and von Willebrand's disease can lead to various abnormalities in platelet and fibrin association with subendothelium [1].
• Platelets from patients with Bernard-Soulier syndrome do not aggregate upon addition of ristocetin although, in contrast to von Willebrand's disease, plasma levels of factor VIII complex (factor VIII clotting activity, von Willebrand factor activity, and von Willebrand antigen) are normal [2].
• Menorrhagia since menarche was noted in 11 (8.9%) of 123 women without a bleeding disorder compared with 13 (65%) of 20 women with von Willebrand's disease (p=0.001) and four (66.7%) of six women with FXI deficiency (p<0.001) [3].
• CONCLUSIONS: This study indicates that most patients with bleeding angiodysplasia or telangiectasia have a deficiency of the largest multimers of von Willebrand factor induced by a latent acquired von Willebrand disease [4].
• With normal and von Willebrand disease (vWD) pigs, we studied the role of von Willebrand factor (vWF) in platelet-vessel wall interactions and occlusive arterial thrombosis [5].

Psychiatry related information on von Willebrand Disease

• Adolescents with menstrual bleeding that is less frequent than every 45 days, is prolonged > 7 days, or is excessively heavy should be evaluated in order to detect conditions such as eating disorders, polycystic ovary syndrome, and von Willebrand disease [6].
• OBJECTIVE: To assess the medical, gynaecological and reproductive experiences of women with von Willebrand's disease (VWD) and to evaluate the impact of VWD on mental health and life activities [7].

High impact information on von Willebrand Disease

• Acquired type I von Willebrand's disease associated with highly substituted hydroxyethyl starch [8].
• Platelet aggregation induced by DDAVP in platelet-type von Willebrand's disease [9].
• Type IIB von Willebrand's disease is a distinct form of this disorder, in which there are abnormal factor VIII/von Willebrand factor multimers in plasma (but normal multimers in platelets) and heightened interaction between the von Willebrand factor and platelets in the presence of ristocetin [10].
• These findings suggest that ristocetin-mediated interactions between platelets and FVIII/vWF do not accurately reflect the "bleeding-time" (von Willebrand factor) defect in this newly described subtype of von Willebrand's disease [11].
• Expression of the phenotypic abnormality of platelet-type von Willebrand disease in a recombinant glycoprotein Ib alpha fragment [12].

Chemical compound and disease context of von Willebrand Disease

• Treatment of von Willebrand disease with two plasma antihemophilic factor (AHF) concentrates, cryoprecipitate and glycine-precipitated AHF, was compared [13].
• Also in plasma from patients with the IIA-type variant of von Willebrand's disease, Factor VIII was protected [14].
• The effects of epinephrine infusion in patients with von Willebrand's disease [15].
• Resistance to arteriosclerosis in pigs with von Willebrand's disease. Spontaneous and high cholesterol diet-induced arteriosclerosis [16].
• A variant of von Willebrand's disease has been identified in which sodium dodecyl sulfate agarose electrophoresis provides evidence that the von Willebrand factor present is structurally abnormal [17].

Biological context of von Willebrand Disease

• Identification of a point mutation in type IIB von Willebrand disease illustrating the regulation of von Willebrand factor affinity for the platelet membrane glycoprotein Ib-IX receptor [18].
• Defective dimerization of von Willebrand factor subunits due to a Cys-> Arg mutation in type IID von Willebrand disease [19].
• Functional analysis of a type IIB von Willebrand disease missense mutation: increased binding of large von Willebrand factor multimers to platelets [20].
• Germ-line mosaicism for a valine-to-methionine substitution at residue 553 in the glycoprotein Ib-binding domain of von Willebrand factor, causing type IIB von Willebrand disease [21].
• The 3' end of the VWF gene was screened in the affected members of 3 different families with type 2A (phenotype IID) von Willebrand disease (vWD) [22].

Anatomical context of von Willebrand Disease

• von Willebrand factor synthesized by endothelial cells from a patient with type IIB von Willebrand disease supports platelet adhesion normally but has an increased affinity for platelets [23].
• 9. A reproducible difference in the IEF pattern of vWF has been established between normal plasmas and those of individuals with variant von Willebrand's disease (vWd) type IIA and type IIB [24].
• Measurement of the von Willebrand factor (vWF) propeptide, also known as von Willebrand antigen II, has been suggested to be helpful in the discrimination of congenital von Willebrand disease type I from type 2 and in assessing the extent of activation of the endothelium [25].
• We examined exon 28 of the von Willebrand factor gene in a patient with both von Willebrand's disease and recurrent bleeding from angiodysplasia in the duodenum as well as his father's, and found a point mutation, C 3916-->T (amino acid substitution; Arg 543-->Trp), in the A1 domain of the von Willebrand factor gene [26].
• In the present studies we report that this high molecular weight endothelial cell-derived von Willebrand factor, when incubated with granulocyte lysates, was cleaved into a series of multimers indistinguishable from those seen in normal plasma (or type II von Willebrand disease) [27].

Gene context of von Willebrand Disease

• Diminished or abnormal vWF activity results in von Willebrand's disease (vWD), a common and complex hereditary bleeding disorder [28].
• In von Willebrand's disease plasma, which was depleted of protein S, APC did not inactivate Factor VIII [14].
• Type 1 von Willebrand disease (VWD), characterized by reduced levels of plasma von Willebrand factor (VWF), is the most common inherited bleeding disorder in humans [29].
• In the latter region of GPIbalpha, the gain-of-function platelet-type von Willebrand disease (PT-vWD) mutations have been identified [30].
• In type 2A (group 2) von Willebrand disease, the mutant vWF is excessively susceptible to cleavage by ADAMTS13, resulting in a decrease of large vWF multimers and bleeding diathesis [31].

Analytical, diagnostic and therapeutic context of von Willebrand Disease

• Epitope mapping of the von Willebrand factor subunit distinguishes fragments present in normal and type IIA von Willebrand disease from those generated by plasmin [32].
• ELISA titers of immunoreactive AHF, using the monoclonal antibody, were closely correlated to those using rabbit antiserum against AHF in normal, hemophilic, and most von Willebrand's disease plasma [33].
• Treatment of von Willebrand disease with a high-purity factor VIII/von Willebrand factor concentrate: a prospective, multicenter study [34].
• The aortic transplantation data are compatible with the hypothesis that the absence of von Willebrand factor in pigs with von Willebrand's disease may cause impairment of platelet-arterial wall interaction and resistance to arteriosclerosis [35].
• Southern blotting was performed with cDNA probes for the human von Willebrand factor (vWF) gene on six patients with severe type III von Willebrand's disease (vWD) [36].

References