Desmopressin therapy to assist the functional identification and characterisation of von Willebrand disease: Differential utility from combining two (VWF:CB and VWF:RCo) von Willebrand factor activity assays?

Potential supplementary utility of combined PFA-100 and functional von Willebrand factor testing for the laboratory assessment of desmopressin and factor concentrate therapy in von Willebrand disease

“…VWF 'activity'/VWF:Ag ratios of 0.7), with the type of discordance helping to identify the probable type of VWD. In this and the previous [15] study, the VWF:CB was used by us as a surrogate marker of high-molecular weight (HMW) VWF, as previously validated and reported [2,3]. Thus, a consistently reduced CB/Ag as well as a consistently reduced RCo/Ag ratio would suggest either VWD type 2A or type 2B, whereas consistently reduced RCo/Ag but consistently normal CB/Ag would suggest a VWD-2M (i.e.…”

“…The current study is an extension of a previous study performed by us that looked at the potential combined benefit of performing VWF:CB testing with VWF:RCo testing, together with DDAVP responsiveness, to help better identify and characterize different VWD patients [15]. That study incorporated data from a total of 208 patients comprising severe type 1 VWD ('VWD1s', n ¼ 17), mild/moderate type 1 VWD ('VWD-1m', n ¼ 30), 'possible mild' type 1 VWD ('VWD-1p', n ¼ 113), haemophilia A/carriers ('HA', n ¼ 19), type 2A VWD ('VWD-2A', n ¼ 19) and type 2M VWD ('VWD-2M', n ¼ 10).…”

“…The current study draws from that pool and incorporates patients where PFA-100 closure times were also available. Patient categories were as per our previous report [15]. Thus, type 1 VWD was defined by consistently low but concordant test values for all VWF tests performed and evident on initial and repeat testing.…”

“…Thus, a consistently reduced CB/Ag as well as a consistently reduced RCo/Ag ratio would suggest either VWD type 2A or type 2B, whereas consistently reduced RCo/Ag but consistently normal CB/Ag would suggest a VWD-2M (i.e. platelet function discordant type [1][2][3]15]). These patterns and classifications are both consistent with the current classification scheme [1] and with previous observations regarding the ability of optimized VWF:CB assays to most appropriately identify HMW VWF [3] more reproducibly than interlaboratory VWF:RCo testing.…”

“…Accordingly, a consistent test pattern comprising reduced RCo/Ag but normal CB/Ag would by definition comprise platelet function discordant VWD-2M and exclude VWD-2A phenotype, and a consistent test pattern comprising reduced RCo/Ag and reduced CB/Ag would most likely reflect a specific loss of HMW VWF, and thus a VWD-2A phenotype. Type 1 VWD was further separated according to 'severity' as previously identified [15], with VWD-1s defined in those with VWF:Ag of 15 U/dl or less, VWD-1m in those with VWF:Ag between 16 and 35 U/dl and VWD-1p in those with VWF:Ag between 36 and 65 U/dl.…”