A Tiered Management Program To Conserve Replacement Therapy Resources for a Rural Population of Women with Type 2M von Willebrand Disease during Labor and Delivery.

Introduction: Type 2M Von Willebrand Disease (VWD) results from a mutation in the Von Willebrand factor (VWF) gene resulting in decreased or absent binding to platelet glycoprotein Ib. Bleeding episodes in type 2M VWD are variable, but can be severe or life-threatening; effective treatment requires administration of exogenous normal VWF. Pregnant women with type 2M VWD require close monitoring to prevent adverse bleeding events. Following a fatal post-partum hemorrhage in a woman from a large kindred with type 2M VWD, routine prophylactic doses of VWF were administered both pre- and postpartum to women with this disorder. This population is uninsured and utilized product is donated for their care. To determine if the amount of VWF could be safely reduced, a tiered risk stratification and replacement therapy program was developed to manage women with type 2M vWD during labor, delivery and the peuperium. We report the results of this tiered risk stratification in terms of the total product utilized and the rate of bleeding experienced. Methods: Between Jan–Mar 2007, we followed 7 Amish women from a large kindred with type 2M VWD (mutation 4120 C-->T on exon 28). This rural community has limited access to sophisticated hematologic monitoring and is uninsured. Women were risk stratified into 1 of 3 tiers (T) based on their personal or immediate family history of bleeding with childbirth. A nurse provided peripartum monitoring via home visits on postpartum days 1, 3, 5, 10 with a portable hematocrit (Hct) machine. Women in T1 were at lowest risk and given VWF replacement only in the event of excessive bleeding or postpartum Hct <30; T2 (intermediate risk) were given a single prophylactic VWF replacement dose immediately prior to delivery then monitored as T1; T3 received prophylactic VWF dose immediately prior to delivery, at 12 hours postpartum, then monitored by serial Hct per the other tiers. Women requiring Cesarean section were placed into T3 but treated with further VWF replacement due to the surgical intervention. Results: The 7 women fell into the following tiers; T1: 4; T2: 2; T3: 1. Of the 4 women in T1, none experienced excessive bleeding and no VWF therapy was required. In the 2 women in T2, there were no bleeding events requiring additional VWF. Postpartum Hct remained >30 on all evaluations in T1 and 2. One woman was delivered by elective caesarean section for complicated twin pregnancy, and given VWF prior to surgery and once daily for three consecutive postoperative days. She had no bleeding complications, and maintained Hct >30. Compared with the prior method of required pre- and post-partum prophylactic VWF administration regardless of tier or Hct, this pilot protocol safely decreased VWF usage in women assigned to T1 and 2 without adverse bleeding outcome or the need for transfusion. Conclusions: Women with type 2M VWD can be safely managed with a tiered risk stratification system and close postpartum clinical/Hct monitoring that utilizes conservative VWF replacement. For T1 and 2 this lead to a reduction in VWF administration of 83% compared with the prior method of mandatory pre- and postpartum VWF administration. This further translated into a substantial cost savings while still achieving safe hemostatic outcomes. Women at highest risk continue to receive prophylactic VWF pre- and postpartum to prevent serious hemorrhagic events.