Thus, VWF levels are reduced in individuals who have a blood group O, and this reduction is secondary to a reduced half-life with a corresponding increase in VWFpp/VWF:Ag ratio [32,33]. Accelerated

clearance of VWF is Ulixertinib in vivo also seen in individuals with an autoimmune antibody to VWF [6]. This results in a rapid clearance of VWF but not VWFpp. Thus, the VWFpp/VWF:Ag ratio is markedly increased. Clinical syndromes with accelerated clearance of VWF are therefore suggested by (i) an elevated VWF/VWF:Ag ratio, (ii) normal platelet VWF:Ag with reduced plasma VWF, (iii) an excessive desmopressin response between steady-state plasma VWF and the 30 min or 1 h assay of plasma VWF or (iv) a reduced mTOR inhibitor VWF survival after desmopressin. Interestingly, when VWF has increased clearance, FVIII also appears to have accelerated clearance. The converse is

not usually seen. If there is an antibody to FVIII (acquired haemophilia), VWF is not usually reduced. With the exception of an acquired antibody to VWF, other causes of reduced VWF are the result of an abnormal host VWF. Treatment with exogenous VWF would be expected to be normal. In contrast, acquired autoimmune VWD will result in accelerated clearance of exogenous VWF. Although infused r-FVIII has a reduced survival in the absence of VWF, that survival is not affected by an antibody to VWF. Thus, continuous FVIII has been clinically effective in some cases of acquired

autoimmune VWD. Few studies have established the biological predictive markers of surgical bleeding in VWD [34,35]. Ziv reported [36] that postoperative bleeding could have been avoided in 83% of the cases if a preoperative family or bleeding history had been obtained. However, until recently, no quantitative description of bleeding symptoms in VWD has been available to fully appreciate their diagnostic relevance to discriminate between a significant bleeding history and trivial symptoms in VWD. A further question for the clinician is whether patients with a history of severe bleeding may be at higher risk of bleeding during invasive procedures (e.g., tooth extraction, surgery). This is clinically relevant, because the laboratory evaluation of mild bleeding disorders selleck chemical has no practical value as a guideline for the optimal antihaemorrhagic prophylaxis, as abnormal laboratory tests do not predict clinical bleeding. In the MCMDM-1VWD study, by using a standardized bleeding questionnaire to establish a bleeding score (BS), the association between spontaneous, mucocutaneous bleeding symptoms (epistaxis, cutaneous bleeding and menorrhagia) and bleeding after surgery or tooth extraction in patients with type 1 VWD was evaluated [37]. Interestingly, the BS showed a predictive value similar to VWF level for bleeding after tooth extraction, but was superior to VWF measurement for the prediction of bleeding after surgery.