VWF can also be assessed by other

methods including multimer analysis to assess for loss of HMW VWF as well as structural abnormalities. In brief, type 1 VWD can be identified as a deficiency of VWF, with the level of deficiency correlating with the find more severity of the disorder. In these cases, low levels of VWF:Ag, VWF:RCo, VWF:CB and other activity assays (‘VWF:Act’) will be determined by laboratories testing patient plasma. However, as the VWF is functionally normal, similar (‘concordant’) levels of VWF will be identified using all VWF assays, and the ratio of any VWF assay to another will be close to one. In practice, a low level of VWF together with a ratio of VWF activity (VWF:RCo, VWF:CB or VWF:Act) to VWF:Ag above 0.7 is consistent with type 1 VWD (Table 1). In contrast, in type 2

VWD, VWF activity based assays will identify some VWF defect, with the defect identified helping to characterize the VWD type. Thus, loss of HMW VWF (present in 2A and 2B VWD) can be identified directly by multimer analysis or indirectly by a relatively larger reduction in VWF:RCo, VWF:CB and VWF:Act click here compared to VWF:Ag. This ‘VWF discordance’ can be expressed by a ratio of VWF activity to VWF:Ag below 0.5–0.7. Type 2M reflects a variety of functional defects, with most representing a platelet GP-Ib binding defect; hence VWF:RCo/VWF:Ag will usually be low, but VWF:CB/VWF:Ag may be normal. Type 2N VWD reflects a loss of VWF-FVIII binding; hence FVIII/VWF:Ag will be low, and phenotypically these patients resemble mild haemophilia A. The main problems relating to laboratory identification of VWD and its type are high inter-laboratory and inter-method assay variability, problems with lower limit of VWF detection, performance of insufficient test panels by laboratories to appropriately define all forms of VWD, and challenges in the interpretation of test findings. Thus, most laboratories struggle with differentiation between severe type 1 vs.

3 VWD, type 2M vs. 2A, 2M vs. 1, 2A vs. 2B, 2N vs. haemophilia A and type 3 VWD vs. haemophilia A. Severe type 1 and 3 VWD can only be distinguished if laboratories perform assays that are capable of detecting VWF levels selleckchem down to <2 U dL−1. Type 2M VWD identification requires performance of VWF:CB in addition to VWF:RCo. As many laboratories do not perform multimer analysis, identification of low VWF:RCo/Ag ratios, may be incorrectly identified as 2A rather than 2M VWD. Alternatively, high inter-assay VWF:RCo variability may lead to false normal VWF:RCo/Ag ratios and misidentification of type 1 VWD. Differentiation of types 2A and 2B VWD requires ristocetin induced platelet aggregation analysis. Differentiation of type 2N and haemophilia A requires performance of a VWF-FVIII binding assay or genetic analysis of the VWF and F8I genes. Type 3 VWD will be misdiagnosed as haemophilia A if FVIII testing is not accompanied by VWF testing.