Use of recombinant activated factor VII for acute bleeding episodes in acquired hemophilia

Abstract

The Hemostasis and Thrombosis Research Society Registry was used to monitor the postapproval use and safety of recombinant activated factor VII (rFVIIa). The objective of this article is to evaluate the data from the Hemostasis and Thrombosis Research Society Registry related to rFVIIa-treated bleeding episodes in patients with acquired hemophilia. For each rFVIIa-treated bleeding episode, the initial dose, total dose, average infused dose, number of doses, and treatment duration were calculated. Efficacy was assessed on a three-point scale. Out of the 166 registered patients with acquired hemophilia, 110 patients were treated for 237 bleeding episodes (139 rFVIIa treated); the majority (70%) were in patients older than 60 years. The most frequently reported bleeding locations were subcutaneous (40%) and mucosal (32%). Subcutaneous bleeding episodes were more commonly reported in women (55% vs. 40% men) and white patients (44 vs. 27% black). Of the 139 rFVIIa-treated bleeding episodes, rFVIIa was used as first-line treatment in 127 bleeding episodes. The median initial dose was 90 μg/kg; the median total dose per episode was 333.5 μg/kg. Physician-rated efficacy of rFVIIa for each bleeding episode was reported as ‘bleeding stopped’ in 85% of bleeding episodes, ‘bleeding slowed’ in 11% of bleeding episodes, ‘no improvement’ in 4% of bleeding episodes, and was not documented in 1 bleeding episode. One thromboembolic event was reported; transient neurologic symptoms were reported in a 31-year-old postpartum patient after 110 doses of rFVIIa. Adequate hemostasis was provided for most rFVIIa-treated bleeding episodes at doses largely conforming to the package insert. No major safety concerns were reported.

Lessons from a systematic literature review of the effectiveness of recombinant factor VIIa in acquired haemophilia

“…1 ) met the inclusion criteria of the review. Additionally, data for three studies were available from reports provided by Novo Nordisk and an external expert (one a clinical study report for the study conducted by Ma et al [ 18 ], the data for which have subsequently been published [ 19 , 20 ], the second a report for the study conducted by Seita et al [ 21 ], which has also subsequently been published [ 22 ], and the last data on file provided by an author [A Tiede]).

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“…(Table 2 ). The percentage of males was higher than females in six of the included studies, ranging from 54% [ 7 ] to 69% [ 27 ], while in four other studies, females were the predominant population (51% [ 20 ]; 59% [ 28 ]; 60% [ 25 ]; 67% [ 29 ]). One study by Hay et al included patients with equal gender distribution [ 30 ].…”

Treatment of acute bleeding in acquired haemophilia A with recombinant activated factor VII: analysis of 10‐year Japanese postmarketing surveillance data

“…Bleeding was considered to be controllable after rFVIIa therapy in 91% of the patients. Data were recently reported on 139 rFVIIa-treated bleeding episodes in 68 acquired haemophilia patients from the Haemostasis and Thrombosis Research Society (HTRS) Registry [17]. Haemostasis was achieved in 135 episodes (97%), while only four bleeding episodes (3%) required change to another haemostatic agent.…”

“…Six cases were myocardial infarction, one was a stroke and four were venous thromboembolism. In the HTRS Registry, only one thromboembolic event was reported among 139 rFVIIa-treated bleeds: a transient ischaemic attack occurred in a 31-year-old postpartum woman with eclampsia and cerebral vasculitis who was treated with 110 doses at 2-h intervals; this event was reported as unrelated to rFVIIa treatment by the investigator [17]. No thromboses were reported during 30 rFVIIa-treated surgical procedures reported in the HTRS Registry [18].…”

A global quantitative survey of hemostatic assessment in postpartum hemorrhage and experience with associated bleeding disorders

“…PPH may be notably delayed in both congenital bleeding disorders and acquired hemophilia, with the latter manifesting as late as 117 days after delivery 4,14,15. Acquired hemophilia is a hemorrhagic disorder often presenting with diffuse soft tissue bleeding and exhibiting refractoriness to factor VIII therapy, and potentially causing life-threatening bleeding symptoms 9,11,16,17. Because of the extreme rarity of this condition, many obstetrician-gynecologists may be unfamiliar with the specialized laboratory assessments necessary to confirm the diagnosis.…”