PB1156 - Desmopressin in hemophilia A carriers: determinants and duration of FVIII response

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

LR

Lorenzo G.R. Romano, MD

PhD candidate
Department of Hematology, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
Rotterdam, Zuid-Holland, Netherlands

Co-Author(s)

Td

Tirza C. den Hertog

Medical student
Department of Hematology, Erasmus MC, Erasmus University Medical Center.
Rotterdam, Zuid-Holland, Netherlands
Greta Mulders-van der Meer, RN

Nurse practitioner
Erasmus MC, Erasmus University Medical Center.
Rotterdam, Zuid-Holland, Netherlands
MC

Marjon H. Cnossen

Associate professor, pediatric hematologist, MD, PhD
Department of Pediatric Hematology, Erasmus MC – Sophia Children’s Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
Frank W.G. Leebeek, MD, PhD

Professor and Head of Department of Hematology
Erasmus MC, University Medical Center Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
MK

Marieke J.H.A. Kruip

Associate professor, hematologist, MD, PhD
Department of Hematology, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands

Background: Desmopressin is a synthetic derivative of vasopressin often utilized in hemophilia A carriers to treat or prevent bleeding as it increases von Willebrand factor (VWF) and endogenous factor VIII (FVIII). Despite its worldwide use, determinants of FVIII response in carriers are largely unknown. Improved insight may increase its therapeutic use which has several advantages.

Aims: To assess the determinants and duration of desmopressin response (FVIII) in hemophilia A carriers.

Methods: Hemophilia A carriers with a historically lowest FVIII < 0.50 IU/mL who received desmopressin (0.3 µg/kg intravenously or subcutaneously) were included. Desmopressin response (FVIII) was measured at 0, 1, 3, 5 and 24 hours (T0-T24) after administration. F8 mutations were categorized according to F8 domain with severity based on male relatives with hemophilia A (severe/non-severe). Desmopressin response was defined as: complete (CR) if measured FVIII level >0.5 IU/mL, partial (PR) if 0.3 - 0.5 IU/mL and non-responder (NR) if < 0.3 IU/mL. Multiple linear regression was used to analyze associations between FVIII peak response (T1) and historically lowest FVIII level corrected for F8 mutation severity and historically lowest measured VWF:Ag.

Results: Fifty-four hemophilia A carriers were included (Table 1). The mean historically lowest FVIII:C measured was 0.36 (SD 0.10 IU/mL). All women showed complete response at T1. At T5 (n=40), 36 carriers (90%) retained CR, and four (10%) PR (Figure 1). The most important determinant for FVIII response was historically lowest FVIII: women with higher historically lowest FVIII (n = 37) presented with a higher absolute peak FVIII response (β=0.454, CI95% [0.29, 3.14] after correction).

Conclusion(s): All hemophilia A carriers had a complete response at T1 after desmopressin administration and retained at least a partial response at T5, with higher absolute peak FVIII response with higher historically lowest FVIII levels. Therefore, desmopressin is treatment of choice in hemophilia A carriers.