Ongoing Effect of Therapeutic rVWF in Patients with Severe VWD

Recently we reported that in vitro addition of recombinant von Willebrand factor (rVWF; Veyvondi) to blood matrix of patients with severe VWD led to a dose-dependent reduction of closure time in the PFA 200 (Pekrul, Kragh et al, 2018). The relevant components are the ultra-large multimers (ULM) of VWF, because conventional plasma products and rVWF without ULM did not normalize primary hemostasis measuring PFA in our VWD patients in vitro and in vivo. Previous studies showed that administration of DDAVP in patients with severe type I VWD led to the release of endogenous VWF and normalization of the PFA (Weston et al, 2009) probably related to ULM. Now we measured closure times of a severe VWD patients receiving rVWF therapeutically and found ongoing effects on primary hemostasis as detected in PFA.

For routine monitoring, blood was taken 1 to 4 hours after administration of rVWF. The closure times in the PFA were measured in addition to standard parameters of the VWF laboratory diagnostics (VWF:Ag, VWF:GP1bM, VWF:CBA).

The administration of 1,300 IU rVWF for a 65-kg patient (VWD type 2A) showed a maximum closure time of ADP/KOLL: 120 s and EPI/KOLL: 148 s after 10 and 20 minutes, respectively. No occlusion was detectable at baseline and 3.5 hours after administration, closure times were >300 s. Doubling the dose (2,600 IU) extended the effect on the closure times accordingly (150 s after 3.5 hours). The VWF:Ag developed from an initial 43% to a maximum of 103 to 80% after 3.5 hours (VWF:GP1bM correspondingly: 5%, 56%, 40%). 1,300 IU rVWF administered to a 52-kg female patient (VWD type 2A) normalized closure time after 10 minutes but no closure was detected 2.5 hours afterward.

In this context, rapid closure of the PFA cartridge indicates the presence of ULM of VWF in our patients. The effect of these multimers is detectable ex vivo for several hours after administration of rVWF depending on the dosage applied.

Publication History

Article published online:
13 November 2020