Gynecologic and obstetric management of women with von Willebrand disease: summary of 3 systematic reviews of the literature

Abstract

Von Willebrand disease, (VWD) disproportionately affects women due to potential issues with heavy menstrual bleeding (HMB), delivery complications, and postpartum hemorrhage (PPH). To systematically synthesize the evidence regarding first line management of HMB, treatment of women requiring/desiring neuraxial analgesia, and management of PPH. We searched Medline and EMBASE through October 2019 for randomized trials, comparative observational studies, and case series comparing the effects of desmopressin, hormonal therapy, and tranexamic acid (TXA) on HMB, comparing different von Willebrand factor (VWF) levels in women with VWD undergoing labor and receiving neuraxial anesthesia and the effects of TXA on PPH We conducted duplicate study selection, data abstraction, and appraisal of risk of bias. Whenever possible, we conducted meta-analyses. We assessed the quality of the evidence using the GRADE approach. We included 1 randomized trial, 3 comparative observational studies and 10 case series. Moderate certainty evidence showed that desmopressin results in a smaller reduction of menstrual blood loss (difference in mean change from baseline, 41.6 [95% CI, 16.6 to 63.6] points in pictorial blood assessment chart score as compared to TXA. There was very low certainty evidence about how first line treatments compare against each other, the effects of different VWF levels in women receiving neuraxial anesthesia, and the effects of TXA administration postpartum. Most of the evidence relevant to the gynecologic and obstetric management of women with VWD addressed by most guidelines is very low quality. Future studies addressing research priorities will be key when updating such guidelines.

von Willebrand disease and von Willebrand factor

“…33,37 Tranexamic acid (1 g iv following umbilical clamping and then 1 g orally every 8 h up to 2 weeks) is generally recommended in women with type 1 VWD and preferably also in those with types 2 and 3. 25 In type 1 pregnant women with FVIII and/or VWF levels lower than 30 U/dl at time of parturition and with evidence of a remarkable positive response, the administration of desmopressin preferably after umbilical clamping to avoid neonate hypotension 29 and for 3-4 days thereafter is required, 31,34 especially if midline episiotomy is required. Monitoring FVIII and VWF levels is advisable, especially when repeated doses are given, together with urinary output and fluid restriction to avoid the risk of hyponatremia.…”

“…Monitoring FVIII and VWF levels is advisable, especially when repeated doses are given, together with urinary output and fluid restriction to avoid the risk of hyponatremia. 26,34 The same approach, with fewer infusions, can be applied to those with VWF >30 and <50 U/dl. The use of VWF/FVIII concentrates may be advisable, especially when close surveillance of the patient is not easily available.…”

“…The use of utero‐tonic agent soon after delivery is recommended similarly to normal women to reduce the risk of bleeding 34 …”

“…All concentrates are equally effective and safe, but the choice should be based according to the associated levels of FVIII and local availability. In presence of high FVIII levels and low VWF observed in women with type 2 VWD, a concentrate with low FVIII is advisable and FVIII and VWF monitoring is recommended during treatment, as well as with the other concentrates 25,26,34 . Similar doses as reported with type 1 should be used.…”

“…In type 1 pregnant women with FVIII and/or VWF levels lower than 30 U/dl at time of parturition and with evidence of a remarkable positive response, the administration of desmopressin preferably after umbilical clamping to avoid neonate hypotension 29 and for 3–4 days thereafter is required, 31,34 especially if midline episiotomy is required. Monitoring FVIII and VWF levels is advisable, especially when repeated doses are given, together with urinary output and fluid restriction to avoid the risk of hyponatremia 26,34 . The same approach, with fewer infusions, can be applied to those with VWF >30 and <50 U/dl.…”