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A. Tiede et al.
Figure 2. Choice and monitoring of hemostatic therapy in acquired hemophilia A. rFVIIa, recombinant activated factor VII (eptacog alfa); APCC, activated prothrom- bin complex concentrate; rpFVIII: recombinant porcine factor VIII (susoctocog alfa), hFVIII, human (plasma-derived or recombinant) factor VIII; h: hour; d: day.
bleeds treated with rFVIIa, were analyzed. The reported median initial rFVIIa dose was 90−105 μg/kg body weight, with ranges between 25−181 μg/kg in individual studies. Doses were repeated mostly every 2−3 h, with the medi- an total number of doses being 10−28. rFVIIa was used as first-line treatment in the majority of cases, and 39−90% of treated bleeds were severe. There was considerable variability across the 12 studies in terms of how hemosta- tic effectiveness was defined. The only effectiveness out- come that provided sufficient data was defined as ‘com- plete’ or ‘partial response’, available for six studies. In five of these six studies, treatment efficacy was >90%, at both patient and bleed levels.
The safety of rFVIIa in AHA was also addressed in the same systematic review.37 Thromboembolic and cardio- vascular events were assessed in eight of the 12 studies and reported in 0−5% of patients. Mortality was included in ten of the studies, with eight reporting no mortality related to rFVIIa. The two studies that reported deaths from thromboembolic events potentially related to rFVIIa were a Japanese surveillance study (2 deaths in 132 rFVIIa- treated patients)39 and the GTH study (3 deaths in 61 rFVIIa-treated patients).10 One patient in the GTH study died from portal vein thrombosis on day 6 while on rFVIIa for 3 days. The other two patients died of ischemic stroke on days 5 and 35 of rFVIIa treatment; these two patients received rFVIIa together with tranexamic acid. In EACH2, thrombotic events were reported in 5/174 (2.9%) patients in association with rFVIIa treatment.8
For initial treatment with rFVIIa, we recommend bolus injec- tions of 90 μg/kg every 2−3 h until hemostasis is achieved (GRADE 1B).
Activated prothrombin complex concentrate
APCC is used for the treatment and prevention of bleeds in patients with congenital hemophilia with
inhibitors,40-42 and is widely used for AHA, although no systematic reviews are available. The recommended dose is 50−100 U/kg every 8−12 h, up to a maximum of 200 U/kg/day.1 In the EACH2 registry, propensity score- matched analysis indicated indistinguishable efficacy for APCC compared with rFVIIa, with >90% bleed control rates when used as first-line treatment.8 An earlier study collected data from 34 cases in three centers in the USA over 10 years.43 A total of 55 bleeding events were observed and the response rate was 76% and 100% for patients with severe and moderate bleeds, respectively.43 APCC has also been used for secondary prophylaxis.44,45
In a retrospective study, APCC exhibited a favorable safety profile indicating that it is well-tolerated with few adverse events.46 Thrombotic events, including myocardial infarction and venous thrombosis, were mostly reported in patients with additional risk factors.46,47 In EACH2, thrombotic events with APCC were reported in 3/63 (4.8%) patients.8 Disseminated intravascular coagulation has been observed following APCC administration in some patients receiving doses higher than 200 U/kg/day.47 APCC is contraindicated in patients with signs of dissem- inated intravascular coagulation.
For initial treatment with APCC, we recommend bolus injec- tions of between 50−100 U/kg every 8−12 h, up to a maximum of 200 U/kg/day (GRADE 1B).
Recombinant porcine factor VIII
Although animal-derived concentrates are no longer available, porcine plasma-derived FVIII concentrate was used extensively in the past for the treatment of AHA because anti-FVIII autoantibodies often exhibited low cross-reactivity with porcine FVIII.48 rpFVIII (susoctocog alfa) was assessed in a prospective, single-arm clinical study.15 Patients with AHA and a serious bleed were eligi- ble, but were excluded if they had an anti-rpFVIII inhibitor
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haematologica | 2020; 105(7)