How I manage pregnancy in carriers of hemophilia and patients with von Willebrand disease

Abstract

Women with inherited bleeding disorders, including carriers of hemophilia A and B, or with von Willebrand disease, have an increased risk of bleeding during pregnancy and delivery. Also the unborn child may be affected by the bleeding disorder for which specific measures have to be considered. This requires a multi-disciplinary approach, including a hematologist, pediatric hematologist, clinical geneticist, obstetrician-perinatologist, and anesthesiologist. An optimal approach includes pre-pregnancy genetic counselling, prenatal diagnostic procedures, and making a treatment plan for delivery for both the mother and child. Recent retrospective studies show that even if strict guidelines are followed, these women are still at risk of postpartum bleeding. This occurs even in case of normalization of coagulation factor levels, either due to the pregnancy-induced rise of factor levels or by infusion of coagulation factor concentrates at the time of delivery. In this article we describe our current diagnostic and clinical management of pregnancy and delivery in women with inherited bleeding disorders. We also briefly discuss possible interventions to improve the outcome of current strategies by increasing target factor levels during and after delivery.

European principles of care for women and girls with inherited bleeding disorders

“…HTCs should draft a clear multidisciplinary birth plan, with an interim plan in place from 24 weeks to cover all eventualities, including preterm delivery, to be adjusted at 28–36 weeks based on reassessment of clotting status and PND results. It includes clear and specific advice regarding haemostatic management during delivery and postpartum, suitability for neuraxial anaesthesia, foetal restrictions requirements for safe delivery (if any) and postpartum neonatal management 45,77–79 . Cord blood testing may be needed and referral for haemostasis testing of possibly‐affected children to a paediatric haematologist.…”

Current Challenges in the Peripartum Management of Women with von Willebrand Disease

“…20 Such restrictions may increase the rate of caesarean section in labor, particularly in the second stage, where the risk of maternal bleeding is greater. 26 Similar to severe hemophilia, some centers offer late amniocentesis to determine if a fetus is affected with type 2 VWD to allow relaxation of restrictions in the event of negative fetal mutational analysis 27 ; maternal hemostatic cover should be provided to ensure that plasma VWF and FVIII levels are 50 IU/dL prior to any invasive procedure. 20 Cord blood sampling and administration of vitamin K by the oral route is recommended for neonates at risk of type 2 and type 3 VWD.…”

“…Several ongoing studies are seeking to address this issue using blood volume based or higher plasma VWF threshold approaches. 27,55,56 A recent publication compared the peripartum use of rVWF (n ¼ 6) or pdVWF (n ¼ 6), both administered at higher doses of 80 IU/kg. 47 Despite this higher prophylactic dose, primary PPH still occurred in 25% of women, with no significant difference between treatment arms.…”

Pregnancy in special populations: challenges and solutions practical aspects of managing von Willebrand disease in pregnancy

“…Genetic test ing and PND are not rou tinely performed in VWD but are con sid ered in fam i lies with type 3 VWD. 2 PND in late preg nancy (usu ally at 34 weeks ' ges ta tion) is also con sid ered in women with severe types of VWD if the muta tion is known to assist man age ment of deliv ery 3,4 ; for exam ple, if the baby is affected, deliv ery can be planned in a ter tiary cen ter, or deliv ery can be man aged with out any restric tions and pos si bly in the local mater nity unit if the baby is unaf fected.…”

“…Labor and deliv ery are asso ci ated with an increase in VWF and FVIII in neo na tes, 26 and thus neo na tes with mild type 1 VWD have a neg li gi ble bleed ing risk. 4 Neonates with type 2 and 3 and severe type 1 VWD still have reduced lev els of VWF and FVIII at birth and have a the o ret i cal risk of increased bleed ing. 27 Despite this the o ret i cal risk, bleed ing risks in neo na tes with VWD, includ ing type 3 VWD, are uncom mon, and life threat en ing intra cra nial hem or rhage is very rare.…”