Type 2B von Willebrand Disease: Early Manifestation as Neonatal Thrombocytopenia

Abstract

Here, we report about a preterm female newborn with a prolonged course of severe thrombocytopenia and hematomas. The family history was positive for von Willebrand disease type 2B (VWD 2B). Diagnosis of VWD 2B was identified analyzing von Willebrand factor (VWF) parameters (VWF:antigen, VWF:activity, VWF multimer analyses) and performing light transmission aggregometry (with half concentration of ristocetin). In addition, the diagnosis was confirmed by molecular genetic analysis: identification of a disease-causing missense mutation (Val1316Met) in the VWF gene associated with a severe course of VWD 2B, which had been previously reported. Treatment with a VWF-containing plasma concentrate was initiated. Because the combination of prematurity and very low platelet count is often associated with intracranial bleeding, at the beginning platelet concentrates were transfused. Fortunately, the patient did not develop serious bleeding episodes. Interestingly, the patient had a mutation in the VWF gene, which had been described to be associated with aggravation of thrombocytopenia especially in stressful situations. Therefore, we replaced venous blood withdrawals by capillary blood samplings when possible and, consequently, we observed an increase of the platelet count after this change in management. At the age of 2 months, the patient was discharged after stabilization of the platelet count without any bleeding signs and without a need of long-term medication.

The Vascular Endothelium and Coagulation: Homeostasis, Disease, and Treatment, with a Focus on the Von Willebrand Factor and Factors VIII and V

“…Type II involves a mutation-derived functional vWF deficiency. Four subtypes have been identified: subtype 2A, which can be subdivided into 2A1, where there is a decreased affinity of vWF for platelets and the subendothelium caused by a deficiency in high-molecular-weight vWF multimers, and 2A2, characterized by increased proteolytic degradation of vWF [ 237 ]; subtype 2B, which involves increased affinity of vWF for platelets, resulting in a depletion of platelets and of vWF itself and increasing the risk of thrombotic episodes [ 238 ]; subtype 2M, where the GPIb glycoprotein complex, responsible for platelet aggregation and adhesion to the vascular endothelium [ 237 ], is reduced or absent; and subtype 2N, where binding of vWF to FVIII is impaired [ 239 ]. Lastly, type III vWD is characterized by a total absence of vWF and by extremely low levels of FVIII (1–9 IU/dl) [ 240 ].…”