Recombinant von Willebrand Factor in Bleeding Patients with Extracorporeal Circulation

Acquired von Willebrand Disease (aVWD) induced by extracorporeal circulation (ECC) is caused by loss of large multimers due to increased shear stress. Information is sparse regarding the contribution of ECC-aVWD to bleeding and wether or how to treat. As compared to plasma derived von Willebrand factor Vonicog alfa (rVWF) contains ultralarge multimers. We present pharmacodynamic data from patients with refractory bleeding who were treated with rVWF on an ultima ratio basis.

Six patients with suspected ECC-aVWD were compared to a patient with congenital vWD (cVWD) type 2, all treated with rVWF (Veyvondi®, Takeda). VWF activity (VWF:Ac) as well as VWF antigen levels (VWF:Ag) (Innovance®, Siemens) were assessed before and immediately after substitution (trough and peak levels). VWF:Ac/VWF:Ag ratios (VWF:R) were used as a surrogate for high-molecular-weight multimers (HMWM). VWF:R < 0.7 was considered indicative of loss of HMWM. Descriptive statistics were used for patient characteristics and therapeutic responses, including absolute and relative as well as body weight related values. n=10 measurements in six patients with ECC-aVWD and n=3 measurements in the patient with cVWD were analysed.

Five out of six patients with suspected ECC-aVWD showed reduced VWF:R (range 0,23-0,64), while trough levels of VWF:Ac and VWF:Ag being normal. In contrast VWF:Ac in the patient with cVWD was reduced to 16%. Overall, increments of VWF:Ac and VWF:Ag after rVWF substitution ranged from +0,4 to +5,5%/1IU/kg b.w. and -0,9 to >2,2%/1IU/kg b.w., respectively. The increase (mean value) of VWF:Ac per 1IU/kg b.w. rVWF was 1,5% and 1,3% in ECC-aVWD and cVWD, as compared to increases of vWF:Ag by 1,4% and 0,9%. Correspondingly, the mean difference between the VWF:R after and before substitution was 0,06 (ECC-aVWD) and 0,3 (cVWD) (0,002 and 0,007/1IU/kg b.w.) Trough levels of VWF:Ac and increment were inversely correlated (r = -0,64).

ECC-aVWD shows reduced VWF:R with normal VWF:Ac. Thus loss of HMWM predominates and rVWF might specifically meet antihemorrhagic needs. Less effective correction of the VWF:R as compared to cVWD points to faster degradation. Overall the efficacy of rVWF substitution is highly variable, but is correlated inversely with trough levels of VWF:Ac. In future studies adressing the antihemorrhagic efficacy of VWF substitution in ECC-VWD, dosing should be targeted by monitoring the VWF:R.

There is no conflict of interest.