Acquired von Willebrand Syndrom (avWS) Typ 2 in children with severe pulmonary arterial hypertension (PAH)

Objective In the last few years there has been found some evidence of an increased degradation of von Willebrand factor and a decrease in high molecular weight multimers in patients with pulmonary arterial hypertension (PAH). One of the first reported cases (Sokkary et al. 2011) was that of a young woman with PAH and menorrhagia suffering from avWS type 2. But apart from this case, very little data has been reported so far. In 2018, a small study was published of 8 children with PAH, all of whom had avWS type 1. Meaning, all multimers were found in all cases. (Pelland-Marcotte et al. 2018).

Material and Methods Based on these available publications we decided to analyse von Willebrand parameters (at least: vWF:Ag, vWF:Ak, multimers) in all patients with severe PAH evaluated for lung transplantation starting in spring 2018.

Results From May 2018 to October 2020 we evaluated 10 children with severe PAH for lung transplantation. Von Willebrand parameters were determined in 8 of these patients. 7 of 8 (87.5 %) patients showed a decrease or loss of high molecular weight multimers, which is typical of avWS type 2. Five of these 7 patients (71 %) had an Ak:Ag ratio <0.8. In the remaining 2 patients the Ak:Ag ratio was 1.4 and 1.6 respectively. However, in these patients a sample error may be considered. The patient with normal von Willebrand multimers showed borderline low vWF:Ak and vWF:Ag, an increased PFA-100 of >300 seconds and pathological aggregation. This patient therefore suffered at least from a platelet dysfunction and possibly also from a mild von Willebrand syndrome type 1.

Conclusion Overall, all children with PAH suffered from a coagulation disorder. Most patients had acquired von Willebrand syndrome type 2. Platelet dysfunction could be another possible coagulopathy that occurs in patients with severe PAH. A ratio of vWF:Ak/vWF:Ag <0.8 and a prolongation of PFA-100 could be early indications of avWS type 2. For all these patients, we recommend an analysis of von Willebrand parameters including multimer analysis, PFA-100 and platelet function testing.

Publication History

Article published online:
18 June 2021