Clinical evaluation of bleeds and response to haemostatic treatment in patients with acquired haemophilia: A global expert consensus statement

Abstract

Background Acquired haemophilia (AH) is a rare bleeding disorder with significant morbidity and mortality. Most patients initially present to physicians without experience of the disease, delaying diagnosis and potentially worsening outcomes. Existing guidance in AH is limited to clinical opinion of few experts and does not address monitoring bleeds in specific anatomical locations. Aim Derive consensus from a large sample of experts around the world in monitoring bleeding patients with AH. Methods Using the Delphi methodology, a structured survey, designed to derive consensus on how to monitor bleeding patients with AH, was developed by a steering committee for completion by a group of haematologists with an interest in AH. Consensus was defined as ≥75% agreement with a given survey statement. After three rounds of survey refinement, a final list of consensus statements was compiled. Results Thirty‐six global specialists in AH participated. The participants spanned 20 countries and had treated a median of 12.0 (range, 1‐50) patients with AH within the preceding 5 years. Consensus was achieved in all items after three survey rounds. In addition to statements on general management of bleeding patients, consensus statements in the following areas were presented: urinary tract, gastrointestinal tract, muscles, skin, joints, nose, pharynx, mouth, intracranial and postpartum. Conclusions Here, we present consensus statements derived from a broad sample of global specialists to address monitoring of location‐specific bleeds and evaluating efficacy of bleeding treatment in patients with AH. These statements could be applied in practice by treating physicians and validated by individual population surveys.

International recommendations on the diagnosis and treatment of acquired hemophilia A

“…Depending on the bleeding site, serial blood count measurements, inspection and palpation of bleeding sites, patient-reported changes in pain or mobility, as well as imaging studies should be taken into consideration. 38 When using rpFVIII treatment, monitoring of FVIII:C can also help to guide subsequent dosing, although clinical efficacy may not always correlate with FVIII:C. 15 Depending on the severity of the condition, failure to improve bleeding symptoms or the appearance of new symptoms may indicate the need for treatment intensification or switching to one of the alternative therapies.…”

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

“…Depending on the clinical circumstances, efficacy assessment and a decision to switch should made after 6 to >24 hours. 28 If time permits, longer time intervals may be justified before switching. In particular, when switching from a bypassing agent to rpFVIII, time may be well spent testing for antiporcine inhibitors to foresee if a switch will be likely successful.…”

Acquired hemophilia in a 7‐year‐old girl successfully treated with recombinant FVIIA and steroids: A case report

“…In case of the absence of antiporcine inhibitors, rpFVIII should be first choice, while in patients with high titers of antibody, bypassing agents should be considered. As for the safety profiles, thromboembolic and cardiovascular events were reported in less than 5% of patients treated with rFVIIa and APCC, while rpFVIIIa had no allergic reactions, thrombocytopenia or thrombotic events compared to plasma derived porcine FVIII 5‐7 . However, as mentioned before, rpFVIII is not indicated for pediatric and adolescent population at the moment.…”

“…First‐line hemostatic treatment choices are represented by bypassing agents: recombinant activated factor VII (rFVIIa; NovoSeven®), activated prothrombin concentrate complex (APCC; FEIBA®), and replacement therapy with recently available recombinant porcine factor VIII (rpFVIII, Obizur®), prior to antiporcine titer evaluation, due to their extremely high efficacy (around 90%). Treatment efficiency and dosage modification are assessed by clinical examination, hemoglobin monitoring, and repeated imaging 5‐7 . However, the use of rpFVIII is not indicated for the pediatric population at the moment, according to European Medical Agency (EMA).…”