Abstract

Background: Acquired hemophilia A (AHA) is a serious bleeding disorder characterized by the formation of autoantibodies against coagulation factor VIII (FVIII). The condition differs from congenital hemophilia A by its strikingly different bleeding phenotype. Also in contrast to congenital hemophilia, the patient's baseline FVIII activity does not seem to correlate with the risk of bleeding as demonstrated in previous registries. The objective of the current study was to reassess the effect of FVIII activity on the risk of bleeding in AHA.

Methods: GTH-AH 01/2010 was a prospective non-interventional study of 102 patients with AHA performed in 29 centers in Germany and Austria. FVIII activity was measured at study baseline and weekly thereafter by local laboratories. FVIII activity was categorized into 5 clinically meaningful intervals: <1%, 1-<5%, 5-<20%, 20-<50%, and ≥50%. Bleeding events were assessed by treating physicians.

Results: A total of 289 bleeds were recorded. 141 bleeds occurred after first diagnosis of AHA; 130 (92%) of those occurred in the first 12 weeks after diagnosis, during an observation period of 1069 patient-weeks. The estimated mean bleeding rate was 0.12 bleeds per patient-week, from weeks 1 to 12 after diagnosis of AHA. Bleeding rate strongly declined with increasing time after diagnosis. A multivariate regression model demonstrated significant effects of the current (weekly) FVIII activity on the weekly bleeding rate (figure), with a clear reduction in bleeding seen when FVIII activity recovered to 20% or higher. Achieving partial remission of AHA (FVIII ≥50%) virtually eliminated the risk of bleeding. A good WHO performance status was also associated with a significantly lower risk of bleeding. Other baseline characteristics, including underlying disorder, concomitant coronary artery disease, heart or renal failure or diabetes mellitus did not influence bleeding rate in the multivariate model. Patients with an average FVIII activity of <1% during weeks 1 to 4 received significantly higher cumulative dose of recombinant factor VIIa (rFVIIa) during this time, potentially explaining that the bleeding rate in those patients was not higher than in patients with a FVIII activity of 1-<5% or 5-<20%.

Conclusion: This study is the first to systematically assess the risk of bleeding during the course of AHA. About 50% of the bleeds in AHA occur after first diagnosis, with a rate of about 0.12 bleeds per patient-week in the first 12 weeks. The bleeding rate is influenced by the current FVIII activity as assessed weekly during this study. Patients with FVIII <1% received more rFVIIa, potentially reducing their bleeding rate as compared to other patients. These results will help to define future strategies for prophylaxis of bleeding in AHA.

Disclosures

Holstein: Novo Nordisk: Consultancy, Research Funding; Shire: Research Funding. Knöbl: Novo Nordisk: Consultancy, Research Funding; Shire: Consultancy, Research Funding. Dobbelstein: Novo Nordisk: Research Funding; Shire: Research Funding. Spannagl: Novo Nordisk: Consultancy, Research Funding; Shire: Consultancy, Research Funding. Heinz: Novo Nordisk: Research Funding; Shire: Research Funding. Scholz: Novo Nordisk: Research Funding; Shire: Research Funding. Eichler: Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Baxalta: Honoraria, Research Funding; Biotest: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Sobi: Honoraria, Research Funding. Huth-Kühne: Novo Nordisk: Consultancy, Research Funding; Shire: Consultancy, Research Funding. Klamroth: Novo Nordisk: Consultancy, Research Funding; Shire: Consultancy, Research Funding. Tiede: Novo Nordisk: Consultancy, Research Funding; Shire: Consultancy, Research Funding.

Author notes

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Asterisk with author names denotes non-ASH members.