Published in:
09-05-2022 | Pharmacokinetics | Case Report
Combination therapy with von Willebrand factor concentrate plus recombinant factor VIII during cesarean section in a patient with type 3 von Willebrand disease and a low inhibitor titer: a case report
Authors:
Yushi Chikasawa, Takeshi Hagiwara, Masato Bingo, Kagehiro Amano, Shigeru Kikuchi, Ayano Mitsuhashi, Keiko Shinozawa, Katsuyuki Fukutake, Ei Kinai
Published in:
International Journal of Hematology
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Issue 4/2022
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Abstract
Type 3 von Willebrand disease (VWD), a rare and severe subtype, can produce inhibitors in roughly 5% to 10% of cases. We present a case of type 3 VWD with inhibitors in late pregnancy, which was successfully managed with a combination of neutralization and factor (F)VIII replacement during cesarean delivery. The patient, a 30-year-old woman, had no history of inhibitors despite over 100 exposures to VWF/FVIII. She developed inhibitors after 28 weeks of weekly pd VWF/FVIII prophylaxis for recurrent urolithiasis-associated hematuria during pregnancy. Genetic analysis detected two novel frameshift mutations: VWF Exon7 c.777_784dup and Exon14 c.1625_1646del. Titers of inhibitors to factors VIII and VWF using the Bethesda assay were 1.2 and 1.1 BU/mL, respectively. Pharmacokinetics revealed significantly low in vivo recovery of FVIII:C and VWF:Rcof and shortened half-life. During cesarean delivery, a combination of bolus pd VWF/FVIII once daily for neutralizing inhibitors plus continuous infusion of recombinant FVIII Fc fusion protein resulted in minimal bleeding without allergic reactions. Both VWF:Rcof and FVIII:C levels increased transiently during the 7-h of combination therapy without thrombotic events. In conclusion, combination therapy with neutralization and continuous FVIII replacement was effective for hemostasis with a low VWD inhibitor titer, though further optimization is required.