Pregnancy and delivery in women with von Willebrand's disease and different von Willebrand factor mutations

Abstract

Background: Pregnancy in von Willebrand's disease may carry a significant risk of bleeding. Information on changes in factor VIII and von Willebrand factor and pregnancy outcome in relation to von Willebrand factor gene mutations are very scanty.

Design and methods: We examined biological response to desmopressin, changes in factor VIII and von Willebrand factor and pregnancy outcome in a cohort of 23 women with von Willebrand's disease characterized at molecular level and prospectively followed during 2000-2007.

Results: Thirty-one pregnancies occurred during the study period. Remarkably, similar changes of factor VIII and von Willebrand factor were observed after desmopressin and during pregnancy in nine women with R854Q, R1374H, V1665E, V1822G and C2362F mutations. Women with von Willebrand's disease and R1205H and C1130F mutations (17 pregnancies in 12 women) had only a slight increase of factor VIII and von Willebrand factor during pregnancy while their response to desmopressin was marked but short-lived. For these women, two to three desmopressin administrations within the first 48 hours were sufficient to successfully manage vaginal delivery. Two women with recessive von Willebrand's disease due to compound heterozygosity for different gene mutations had a spontaneous, major increase in factor VIII while von Willebrand factor remained severely reduced. Desmopressin increased factor VIII and was clinically useful in the first case, while a factor VIII/von Willebrand factor concentrate was required in the second patient not responsive to the compound. Factor VIII/von Willebrand factor concentrate was also required for two women with type 2 A von Willebrand's disease with V1665E mutations who had no von Willebrand factor activity change during pregnancy. In one of them, delayed bleeding occurred 15 days later requiring treatment with Factor VIII/von Willebrand factor concentrate. No miscarriages or stillbirths occurred.

Conclusions: Close follow-up and detailed guidelines for the management of parturition have produced a very low rate of immediate and late bleeding complications in this setting. Desmopressin was effective and safe in preventing significant bleeding at delivery in most of these patients.

Figure 1.

Upper part. FVIII:C and VWF measurements before and after desmopressin infusion (0.3 μg/kg body weight). For women with R1205H and C1130F mutations, the results are the average ± SD of a single test in six patients each, for V1822G the results are of a single test, for C2362F the results are the average ± SD of a single test in three patients, for R854H the results are the average for two patients. Lower part. FVIII:C and VWF changes during 12, 24 and 36 weeks of pregnancy. For R1205H and C1130F, the results are the average ± SD of a single pregnancy in six patients each, for V18229 the average of two pregnancies for C2362F, the average ±SD of a single pregnancy in three patients and for R854Q, the average of two pregnancies.

Figure 2.

Upper part. FVIII:C and VWF measurements before and after desmopressin infusion (0.3 μg/kg body weight). For C2671Y/deletion, 1534-3C>A intron 13/Q77X and R1374H, the result of a test-infusion is reported, for V1665E the average of the results of a test-infusion in two patients is reported. Lower part. FVIII:C and VWF changes at 12, 24 and 36 weeks of pregnancy. The results represent the mean of two different pregnancies, apart from the patient with C2671Y/gene deletion.