Successful Management of Pregnancy with Severe Von Willebrand Disease in a Jehovah's Witness with Recombinant Von Willebrand Factor

Abstract

Background: Von Willebrand disease (vWD) is the most common inherited bleeding disorder with a reported prevalence of 1% in epidemiological studies and symptomatic prevalence of 1 in 10,000.Pregnancy in vWD is associated with increased bleeding risk particularly postpartum hemorrhage. Treatment options include desmopressin acetate (DDAVP), plasma derived factor concentrates and antifibrinolytic agents. Human Recombinant von Willebrand factor (vWF) (Vonvendi®) has been approved in the United States for on demand treatment and perioperative management of adults with vWD. It has been shown to maintain sustained levels of VWF activity but requires co-administration with FVIII to achieve adequate FVIII levels. Recombinant VWF is an option for patients who refuse blood for religious reasons.Case: Here we describe a 39 year old patient in her third pregnancy who is a Jehovah's Witness. Consent was obtained from the patient for this report. She was initially diagnosed with von Willebrand's disease at the age of six, when she had hematuria. At the age of 11, with menarche, she had significant menorrhagia resulting in symptomatic anemia, a reduction in her hemoglobin concentration to 44 g/L, requiring uterine artery embolization. She was placed on an oral contraceptive pill for menorrhagia. She used DDAVP for trauma induced injury. Her first pregnancy resulted in spontaneous abortion. She required a D&C and DDAVP was used. Prior to delivery of the second pregnancy DDAVP was used but she had postpartum hemorrhage, requiring additional dosing of DDAVP and uterine artery embolization.In the current pregnancy, aPTT was 36.4 seconds with normal PT and platelet count and blood group O. At 15 weeks' gestational age, VWF antigen (ACL TOP 700 -IL HemosIL) was 0.11 units/ml (normal range for blood group O 0.45-1.5 unit/ml), ristocetin cofactor (ACL TOP 700 -IL HemosIL), 0.09 units/ml (normal range 0.48-2.0 units/ml for blood group O), and FVIII level (Sysmex CS5100 -Dade Actin FS) 0.09 units/ml (normal range 0.58-1.9 units/ml). Factor levels at 23 weeks' gestation 1 hour following DDAVP were FVIII 1.05 units/ml, VWF antigen 0.5 units/ mL, and ristocetin cofactor 0.52 units/ml. She was willing to accept recombinant factor concentrates only.Results: She had an elective admission for induction of labor at 37 weeks but proceeded to Cesarean Section due to non-progression of labor. Her PTT on admission was 40 seconds with VWF antigen of 0.11 units/ml, VWF activity < 0.07 units/ml and FVIII 0.13 units/ml. The Table describes her levels following the administration of recombinant vWF. She was administered Vonvendi® on a planned dose of 40 IU/kg Xynta® and rFVIII 30 IU/kg to increase factor levels to more than 50%; 60-min following infusions vWF : RCo was 0.64 U/ml with FVIII 0.79 U/ml. The Cesarean section was performed under spinal anesthesia without complications. Tranexamic acid was used intravenously before the delivery of the neonate and continued for first two days and then changed to oral dose.Target levels were achieved over the 5 days after delivery with the current regimen. She experienced a transient hypersensitivity reaction with urticaria and dyspepsia after the third dose of Vonvendi®. She did not have significant bleeding. Her hemoglobin concentration remained stable at 120 g/L throughout her inpatient stay.The neonate did not have bleeding with delivery but was found to have VWF antigen of 0.11 U /ml, VWF activity of 0.07 U/ml and FVIII of 0.16 U/ml. Genetic analysis of the mutation associated with her vWD is in progress.Conclusion: The use of rvWF and rVIII resulted in adequate hemostasis peripartum. Further prospective data are required to reaffirm the safety and dosing of rvWF for peripartum management of patients with vWD who require intervention. DisclosuresKazi:Shire: Other: Vonvendi was provided by Shire.