Delays in the diagnosis of acquired hemophilia A (AHA) represent an important clinical challenge and may lead to prolonged bleeding and poorer outcomes. Therefore, the authors of a new study published in Cureus proposed an algorithm that might aid in the early diagnosis and treatment of AHA, particularly in nonspecialized settings.
The algorithm proposes the following initial steps:
- Identification of a patient with new, unexplained bleeding
- Detailed clinical history, including medication use and a thorough physical examination
- Primary laboratory testing, including a complete blood count, a metabolic panel including creatinine and bilirubin, and coagulation testing including activated partial thromboplastin time (aPTT) and prothrombin time with international normalized ratio
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If isolated aPTT elevation is observed, the patient should be referred for an early inpatient hematology consultation and an aPTT mixing study and a factor VIII activity (FVIII:C) should be ordered, the authors said. They then recommend the following steps to prevent further delay in patients’ recovery and, eventually, reduce complications:
- If the mixing study result is abnormal with low FVIII:C, then initiate hemostatic treatment plus concurrent confirmatory Bethesda assay or anti-FVIII enzyme-linked immunosorbent assay (ELISA)
- If the mixing study result is abnormal with normal FVIII:C, then repeat with incubation
- If the mixing study result is abnormal after incubation, then confirm Bethesda assay or anti-FVIII ELISA; if positive, initiate treatment
“If there is limited availability of specialty testing or prolonged delays in getting test results, such as for FVIII:C, or an inability to confirm a diagnosis at any stage of the algorithm, transferring the patient to a higher level of care with these laboratory and hematology services should be strongly considered,” the authors recommended.
The study enrolled 6 patients who met the criteria for AHA diagnosis (median time to diagnosis, 14 days from bleeding onset). Half of the patients had cancer, and one patient died before treatment initiation.
The others received recombinant factor VIIa (NovoSeven®), and 2 required a second-line bypassing agent, recombinant porcine sequence factor VIII (Obizur®). Although all patients achieved hemostasis, all died within a 5-year period, 4 of whom directly from bleeding complications.
Fragner M, Imbo B, Hobson J, et al. Time is blood: the impact of diagnostic delays on acquired hemophilia A. Cureus. Published online February 9, 2022. doi:10.7759/cureus.22048