Because cysteines are involved, many if not all of these mutations can be diagnosed by multimer analysis. Although the VWF seems to be dysfunctional, DDAVP therapy is able to normalize not only the concentration but also the function of the protein in most if not all the patients [58]. Budde et al. have found that 22% of type 1 patients show this peculiar multimer pattern (i.e. 75 per year in their laboratory). A grey zone certainly exists, but the implementation

of multimer analysis as a first-line test together with an antigen and functional tests will detect 13% of patients within the grey zone who definitely have inherited VWD or AVWS. The pharmacokinetics of VWF has been studied in adults, selleck inhibitor but there are few data investigating the pharmacokinetics of VWF in children and adolescents. This section reviewed the pharmacokinetics of VWF throughout a patient’s lifespan. The aims of

treatment of VWD are to correct the abnormal platelet adhesion due to reduced and/or dysfunctional VWF and to increase the low level of factor VIII. The principles of treatment of VWD are as follows: Accurate diagnosis of the individual patient’s VWD type and baseline VWF:RCo and FVIII:C activity; Assessment of the severity of the haemorrhage to be treated or procedure to be performed; Determination of DDAVP responsiveness in a non-bleeding state; Knowledge of the VWF:RCo and factor VIII:C content of the product to be used if replacement therapy is necessary; Plan for monitoring when treating severe bleeds/major surgery; Plan for intervention if bleeding occurs despite recommended therapy [59]. There are intrinsic selleck products difficulties when studying pharmacokinetics in VWD. Problems include the heterogeneity of the disease (type 3, severe type 1, types 2A and 2M) and low compliance of patients involved

in pharmacokinetic studies. In a model of FVIII cycle in type 3 patients, at least for the first hour there is a plateau effect Rho due to an increase in FVIII concentration. Most pharmacokinetic studies in VWD patients do not fulfil the golden rule of general pharmacokinetics: the concentration of drug must decay to the baseline value at the end of single dose kinetics. In a study to investigate the effect of four plasma concentrates in 10 patients with severe VWD, none of the concentrates consistently normalized the bleeding time in a sustained manner [60]. The concentrates studied were an intermediate-purity, pasteurized FVIII–VWF concentrate (Humate-P); an intermediate-purity, dry-heated FVIII–VWF concentrate (8Y); a solvent/detergent-treated VWF concentrate, containing little FVIII (lot 87 9000 80); and a high purity solvent/detergent-treated FVIII–VWF concentrate (Alpha VIII). All concentrates were equally effective in attaining normal and sustained levels of FVIII:C postinfusion, although peak levels were more delayed after the VWF concentrate.