Type 2B von Willebrand disease – a rare cause of neonatal thrombocytopenia

Objective Von Willebrand disease (VWD) type 2B is a rare hereditary disorder characterized by activating mutations in the von Willebrand factor (VWF) gene leading to spontaneous platelet aggregation and variably pronounced thrombocytopenia and coagulopathy. Treatment is primarily based on VWF substitution. Management of VWD 2B in the neonatal period is not standardized and only few case reports exist. Here, we present the case of a newborn with a prolonged course of thrombocytopenia caused by VWD 2B.

Material and Methods Standard laboratory assays for the assessment of VWF activity and antigen were used. VWF multimers were analyzed using agarose gel electrophoresis. Ristocetin-induced platelet agglutination (RIPA) was performed using low-dose ristocetin concentration (≤ 0.6 mg/ml).

Results The female newborn presented with hematomas and thrombocytopenia (11/nl) on the 4th day of life. Family history was notable for a suspected VWD 2B of the patient’s father. Initial laboratory exams revealed a low VWF activity to antigen ratio of 0.39. VWF therapy was started because of high suspicion for a VWD 2B. Platelets were administered to treat severe thrombocytopenia. Multimer analysis showed loss of high molecular weight VWF multimers. RIPA with half of the ristocetin concentration (reaching 70% of maximal aggregation) found in this patient is typical for VWD 2B. The diagnosis was confirmed by detection of a known disease-causing heterozygous missense mutation (V1316M) in the VWF gene which is known to be related to severe thrombocytopenia and bleeding diathesis, especially in stressful situations (infections, surgery). Close-meshed clinical and ultrasound exams ruled out new bleeding episodes. Laboratory controls showed increasing platelet counts under VWF substitution and also when substitution was stopped. Capillary blood withdrawals were preferred to venipuncture to reduce stressful events. After discharge from hospital, no new bleeding episodes occurred so far.

Conclusion VWD 2B is a rare cause of neonatal thrombocytopenia. VWD 2B is strongly suggested by RIPA and confirmed by molecular genetic analysis. The mutation of this patient is related to a severe course. Further bleeding episodes were prevented by prompt initiation of VWF substitution. As stressful events can enhance the degree of thrombocytopenia, capillary blood withdrawals should be performed if the patient carries this variant of the VWF gene.

Publication History

Article published online:
18 June 2021