Critical Bleeding in Acquired Hemophilia A: Bypassing Agents or Recombinant Porcine Factor VIII?

Introduction

Patients with acquired hemophilia A (AHA) often present in an emergency setting to physicians not specialized in bleeding disorders.[1] If symptoms and laboratory signs are appropriately recognized, physicians will usually consult with experts, who will guide management of the initial bleed, either remotely or after patient referral. In patients with clearly acquired bleeding, isolated prolongation of the activated partial thromboplastin time, and low factor VIII (FVIII) activity, the suspicion of AHA is likely enough to warrant hemostatic treatment in the case of significant bleeding. If time permits, the FVIII inhibitor titer will be quantified by the Bethesda assay (in Bethesda units [BU]/mL), and differential diagnoses (like the acquired von Willebrand syndrome[2] or lupus anticoagulant) will be excluded by appropriate testing, before treatment is commenced.[3] [4]

Although the diagnosis of AHA is usually clear-cut,[5] significant delays occur because of lack of awareness by nonexpert physicians. The European Acquired Hemophilia Registry (EACH2) documented a diagnostic delay of more than a week in 35% of patients, and the median time to start of hemostatic treatment was 20 days in these patients.[6] Delayed diagnosis and treatment may result in the accumulation of more severe tissue damage, in particular of large muscle hematomas, making hemostatic treatment more difficult and failure more likely. In EACH2, the only parameter that differed significantly between patients who responded to treatment and those who did not was a delay in time to treatment (median: 1 vs. 4 days).[7]

This narrative review article discusses the optimal use of existing hemostatic treatment options for patients with AHA, with emphasis on advantages and potential risks of particular agents in certain clinical situations.

The drugs discussed herein are summarized in [Table 1]. The inclusion of the bypassing agents (recombinant factor VIIa [rFVIIa] and activated prothrombin complex concentrate [APCC]) as well as recombinant porcine FVIII (rpFVIII) is based on their European Union (EU) licensing status for AHA and international treatment recommendations.[1] Plasma-derived and recombinant human FVIII concentrates are used only if other treatment options are not available and are therefore not discussed here.

Table 1 Hemostatic agents to treat acute bleeds in AHA

Agent	Recommended starting dose and interval	Laboratory monitoring	Hemostatic effectiveness	Thromboembolic risk
Bypassing agents
Recombinant factor VIIa (eptacog alfa activated, NovoSeven)	90 µg/kg q 2–3 h	None	Systematic review: 84–96%[12] Registries: EACH2 91%[7]	Systematic review: 0–5%[12] Registries: EACH2 2.9%[7]
Activated prothrombin complex concentrate (FEIBA)	50–100 U/kg q 8–12 h[a]	None	Systematic review: not available Registries: EACH2 93%,[7] US 76–100%[30]	Systematic review: not available Registries: EACH2 4.8%[7]
Recombinant porcine FVIII
Susoctocog alfa (Obizur)	200 U/kg q 4–12 h	FVIII one-stage clot assay • 30 min and 3 h after first dose • Before and 30 min after subsequent doses	Systematic review: not available Clinical trial: 100% effective or partially effective at 24 h; 86% control of qualifying bleed[14]	Systematic review: not available Clinical trial: 0%[14]

Abbreviations: AHA, acquired hemophilia A; EACH2, The European Acquired Hemophilia Registry.

^a Maximum daily dose of 200 U/kg body weight must not be exceeded.

Publication History

Received: 18 March 2020

Accepted: 05 May 2020

Article published online:
11 September 2020

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