Through the addition of the ristocetin to the platelet rich plasma, an evaluation of the affinity of VWF to the platelets in the patients plasma is performed [12]

Through the addition of the ristocetin to the platelet rich plasma, an evaluation of the affinity of VWF to the platelets in the patients plasma is performed [12]. Three concentrations between 0. 5 and 1 . 5mg/mL are used. routine tests are the bleeding time, the activated partial thromboplastin time and the platelet count, however , singly, they may not suggest the diagnosis of VWD, requiring further Allopregnanolone specific tests, such as VWF function evaluation through its ristocetin cofactor assay (VWF: RCo), VWF protein concentration immunoassay (VWF: Ag), the factor VIII coagulation assay (FVIII: C), VWF binding to immobilized collagen (VWF: CB), ristocetin-induced platelet aggregation (RIPA), VWF multimers patterns, factor VIII binding of immobilized VWF (VWF: FVIIIB), among others. From the moment the diagnosis is confirmed, the appropriate treatment for each patient is sought, with the purpose of increasing plasma concentrations of the deficient protein, both in bleeding episodes, as for invasive procedures. Although diagnosis facilitates treatment other approach in the present scenario is prenatal diagnosis which, is the need of the hour. Keywords: Von Willebrand disease, Von Willebrand factor, Platelet count, Platelet aggregation, Ristocetin cofactor == Introduction == Hemostasis maintains fluidity of the blood not allows bleeding or thrombosis [1]. A bleeding disorder usually happens when there is defective hemostasis, CD178 meaning that clotting is compromised [2]. Bleeding disorders can be hereditary or acquired. They are characterized by bleedings of varying intensity related to hematologic diseases or systemic situations [1]. Von Willebrand disease (VWD) is the most frequent hereditary hemorrhagic disease and its prevalence varies between 0. 8 and 2 % in the population, according to studies of population screening [3]. The prevalence of clinically significant disease is probably closer to 1: 1000, being an extremely heterogeneous and complex disorder that is related to deficiency in concentration, structure or function of von Willebrand Allopregnanolone factor (VWF) [4]. VWF is a multimeric glycoprotein structure, synthesized by endothelial cells in WeibelPalade bodies and megakaryocytes, its found in plasma and in the platelets. [5]. VWF is formed by identical sub-units, which have binding sites for both platelet glycoproteins and collagen [6]. VWF links the platelets to the lesioned subendothelium through its binding to the collagen, this is the function of VWF in the platelet adhesion which triggers the activation of the platelets with consequent aggregation. Another important function is the binding to the plasmatic FVIII, this binding prevents the degradation of the FVIII and extends the plasmatic half-life [3]. In 1926, Erich von Willebrand described the hereditary form of VWD for the first time. Allopregnanolone At the time, the hypothesis sustained that it was a problem in platelet function or a vascular modification [7]. Years later, it was found that a mutation in the gene responsible for the coding of VWF occurs and it is located in the chromosome 12 short arm [1]. An update classification system has been proposed in 2006, from then the VWD was classified into three major categories: type 1, partial deficiency in VWF concentration; type 2, qualitative defects in VWFs molecule and it is sub-divided into 2A, 2B, 2M, 2N; and type 3, that shows total deficiency in the concentration of VWF [8]. The qualitative defects sub-divided into four types are described as: type 2A, a variant with altered platelet function and is associated with the loss of VWF high molecular weight multimers; in type 2B, VWF has more affinity to the platelet membranes receptor Ib; the type 2M shows alterations in the platelet function without being associated to the loss of high molecular weight multimers; and the type 2N has a smaller affinity to FVIII [9]. The type 2B is responsible for less than 5 % of VWD cases [10]. In these cases, the mutations in a single amino acid in the gene A1 domain result in an increase of the von Willebrand factor binding to the GP-lb platelet receptors, causing the increase in the depuration of.