A comparative study in patients with type 2 von Willebrand disease using 4 different platelet-dependent von Willebrand factor assays

Reply to “Comment on: A comparative study in type 2 von Willebrand disease patients using four different platelet-dependent von Willebrand factor assays”

“…We agree that this quality control survey can be very useful in establishing the sensitivity and specificity of diverse assays evaluating samples from patients with different types of von Willebrand disease (VWD) [ 1 ]. In our manuscript [ 2 ], we focused only on the assays that measure the platelet-dependent von Willebrand factor (VWF) activity using either platelets and ristocetin (VWF:RCo) or gain-of-function recombinant glycoprotein (GP) Ib molecules (VWF:GPIbM), with the goal to investigate the possible advantages or disadvantages of these 2 methods among a heterogeneous group of patients with type 2 VWD. All investigated cases have been characterized at both biochemical and molecular levels and classified following the International Society on Thrombosis and Haemostasis guidelines.…”

“…Moreover, we take the opportunity to evaluate our results by applying the cutoff of 0.7 for the platelet-dependent VWF activity/VWF:Ag ratio as suggested to discriminate type 1 from type 2 patients with VWD in the new guidelines [ 3 ]. The graphical abstract [ 2 ] showed the percentage of the correct diagnosis and misdiagnosis obtained in each VWD type group with the 4 different assays using either 0.6 or 0.7 as cutoff. Contrary to what was reported by Favaloro [ 1 ], it is clear that the misidentification does not concern only the type 2B without HMWM but also the type 2A, 2M, and 2M/2A patients.…”

“…Contrary to what was reported by Favaloro [ 1 ], it is clear that the misidentification does not concern only the type 2B without HMWM but also the type 2A, 2M, and 2M/2A patients. Hence, the choice of 0.6 or 0.7 as a cutoff affects all groups of type 2 evaluated in our study, with the obvious exception of the 2B with HMWM, behaving as type 1 VWD [ 2 ]. This finding emphasized this critical aspect and how the diagnosis of type 1 or type 2 VWD in patients with “borderline” platelet-dependent VWF activity/VWF:Ag ratios should not rely only upon this feature.…”

“…Since only 9 type 2M patients were evaluated in our study [ 2 ], we herein investigated 9 additional patients ( Table ) to further examine the limitations of the commercial VWF:GPIbM assay with this VWF variant often being misdiagnosed as type 1. At variance with our previous findings [ 2 ], all investigated cases, with a single exception, were correctly diagnosed by both assays. Nevertheless, the VWF:GPIbM assay appears to marginally overestimate these patients compared with the VWF:RCo assay.…”

“… a Patients carrying the same variant are related. The assays used to evaluate type 2M patients were performed as reported previously [ 2 ]. …”