Thrombocytopenia associated with pregnancy in a patient with type IIB von Willebrand's disease

Abstract

Thrombocytopenia may accompany variant (type IIB) von Willebrand's disease (vWD) and is thought to result from binding of the abnormal von Willebrand factor (vWF) to the patient's platelets with subsequent platelet aggregate formation and clearance. We have studied a patient with type IIB vWD who became thrombocytopenic during two pregnancies. During the third trimester of pregnancy, her platelet counts dropped to 20,000 to 30,000/microL, and an increase in the intermediate-sized vWF multimers was seen on agarose gel electrophoresis. During this time her platelet-rich plasma showed spontaneous platelet aggregation, and her plasma caused spontaneous aggregation of normal washed platelets. Antibody to platelet glycoprotein Ib completely blocked the spontaneous platelet aggregation, while antibody to platelet glycoprotein IIb/IIIa did not block the response at the concentrations used. Inhibitors of platelet function that elevate platelet cyclic AMP also blocked the response, but aspirin had no effect on the spontaneous platelet aggregation. The patient illustrates that the platelet counts in one individual can vary greatly in type IIB vWD and that the thrombocytopenia that occurs can appear under physiologic conditions that stimulate the endogenous production of the patient's abnormal vWF. The mechanisms leading to spontaneous platelet aggregation and thrombocytopenia appear to be similar to those described for other patients with type IIB vWD.

Pregnancy in women with von Willebrand's disease or factor XI deficiency

“…This may explain the lack of clinical improvement in pregnancy and the greater risk of postpartum haemorrhage in these women than those with type 1 von Willebrand's disease 11 . In addition, women with subtype 2B may develop worsening thrombocytopenia during pregnancy 16 due to increased production of the abnormal intermediate von Willebrand factor multimers. These multimers bind to platelets and induce spontaneous platelet aggregation.…”

“…Therefore, it is essential to monitor both von Willebrand factor antigen and activity levels, together with factor VIII procoagulant activity during pregnancy. The platelet count should also be monitored in type 2B women 16 . In women with factor levels < 50 IU/dL during the third trimester, appropriate prophylactic therapy for delivery requires correction of the quantitative and or qualitative von Willebrand factor defect, in addition to elevation of factor VIII levels.…”

Haemorrhagic problems in obstetrics and gynaecology in patients with congenital coagulopathies

“…Patients with type IIB von Willebrand's disease may pose slightly different problems. They can develop thrombocytopenia due to binding of the abnormal intermediate sized multimers of vWF:Ag to platelets and inducing spontaneous platelet aggregation and subsequent thrombocytopenia (Rick et al 1987). This is more likely to occur in pregnancy, when there is a stimulus to vWF:Ag production resulting in a high concentration of these abnormal multimers.…”

“…This is more likely to occur in pregnancy, when there is a stimulus to vWF:Ag production resulting in a high concentration of these abnormal multimers. Such patients need careful monitoring in pregnancy and may require treatment with both platelets and vWF containing blood products (Rick et al 1987).…”

von Willebrand disease (VWD): evidence‐based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA)1

“…Although laboratory results for type 2B VWD may be similar to those in type 2A or type 2M VWD, patients with type 2B VWD typically have thrombocytopenia that is exacerbated by surgery, pregnancy or other stress [62–64]. The thrombocytopenia probably is caused by reversible sequestration of VWF‐platelet aggregates in the microcirculation.…”