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Clinical Trial
. 2020 Jul 16;136(3):279-287.
doi: 10.1182/blood.2019003639.

Bleeding and response to hemostatic therapy in acquired hemophilia A: results from the GTH-AH 01/2010 study

Katharina Holstein  1 , Xiaofei Liu  2 , Andrea Smith  2 , Paul Knöbl  3 , Robert Klamroth  4 , Ulrich Geisen  5 , Hermann Eichler  6 , Wolfgang Miesbach  7 , Andreas Tiede  8
Affiliations
Clinical Trial

Bleeding and response to hemostatic therapy in acquired hemophilia A: results from the GTH-AH 01/2010 study

Katharina Holstein et al. Blood. .

Abstract

Acquired hemophilia A (AHA) is due to autoantibodies against coagulation factor VIII (FVIII) and most often presents with unexpected bleeding. In contrast to congenital hemophilia, the patient's residual FVIII activity does not seem to correlate with the risk of bleeding as suggested from previous studies. Risk factors for bleeding have not been described. We used data from the prospective GTH-AH 01/2010 study to assess the risk of bleeding and the efficacy of hemostatic therapy. FVIII activity was measured at baseline and weekly thereafter. Bleeding events were assessed by treating physicians. A total of 289 bleeds were recorded in 102 patients. There were 141 new bleeds observed starting after day 1 in 59% of the patients, with a mean rate of 0.13 bleed per patient-week in weeks 1 to 12, or 0.27 bleed per patient-week before achieving partial remission. Weekly measured FVIII activity was significantly associated with the bleeding rate, but only achieving FVIII activity ≥50% abolished the risk of bleeding. A good World Health Organization performance status assessed at baseline (score 0 vs higher) was associated with a lower bleeding rate. Hemostatic treatment was reportedly effective in 96% of bleeds. Thus, the risk of new bleeds after a first diagnosis of AHA remains high until partial remission is achieved, and weekly measured FVIII activity may aid in assessing the individual risk of bleeding. These results will help to define future strategies for prophylaxis of bleeding in AHA.

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Conflict of interest statement

Conflict-of-interest disclosure: K.H. received honoraria for advisory boards or speaker fees from Bayer, Biotest, Chugai, CSL Behring, Novo Nordisk, Pfizer, Roche, Shire/Takeda, and SOBI; and unrestricted research grants from Bayer, CSL Behring, and Pfizer. P.K. received honoraria, consultation and speaker fees, and research and travel grants from Biotest, CSL Behring, Novo Nordisk, Octapharma, Roche, Sanofi, and Baxalta/Shire/Takeda. R.K. received research funding and honoraria from Bayer, BioMarin, Biotest, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, SOBI, and Takeda. U.G. received honoraria for advisory boards and travel grants from Roche, Bayer, and Baxalta/Shire/Takeda. H.E. received honoraria or consultation fees, advisory boards or speaker fees, and research grants from Bayer, Biotest, CSL Behring, Novo Nordisk, Pfizer, Roche, Shire, and SOBI. W.M. received honoraria, research grants, and consultation fees for participating at educational meetings organized by Alnylam, Bayer, Biogen Idec, Biotest, Chugai, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and SOBI. A.T. received honoraria or consultation fees for participating at educational meetings organized by Alnylam, Bayer, Biogen Idec, Biotest, Boehringer Ingelheim, Chugai, CSL Behring, Daiichi Sankyo, Leo Pharma, Novo Nordisk, Octapharma, Pfizer, Portola, Roche, Shire, and SOBI. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Kaplan-Meier analysis of bleeding risk according to baseline characteristics and remission status. (A) Frequency of patients with bleeding event after day 1 of study (102 patients; red line, total bleeds; blue line, treated bleeds only) and after the day of first PR (81 patients; green line, total bleeds). All events include recurrent and nonrecurrent bleeding events. (B) Frequency of patients with bleeding event after day 1 according to baseline FVIII activity (102 patients). (C) Frequency of patients with bleeding event after day 1 according to baseline FVIII inhibitor (102 patients). In all panels, patients no longer at risk (because of death or end of follow-up) were censored.
Figure 2.
Figure 2.
Rate of total bleeds in weeks 1 to 12. The bars show crude numbers of observed bleeds (red bars) in patients alive (blue bars) according to treatment week (left y-axis). Circles show the mean estimated weekly bleeding rate according to negative binomial distribution for patients alive (right y-axis).
Figure 3.
Figure 3.
FVIII activity over time. FVIII activity was assessed at least weekly by local laboratories. Filled areas show the absolute number of patients in each FVIII activity category over time. Week 0 refers to the last 7 days before day 1. If more than one FVIII activity was available in a week, the lowest activity was used for analysis.
Figure 4.
Figure 4.
Model-estimated bleeding rate according to treatment week and current FVIII activity.
Figure 5.
Figure 5.
Hemostatic treatments and treatment success (bleed level).
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Comment in

References

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