Undiagnosed Acquired Hemophilia A: Presenting as Recurrent Gastrointestinal Bleeding

Abstract

Acute gastrointestinal bleeding (GIB) is a frequently encountered medical emergency and it can be lifethreatening depending on the etiology and the clinical condition of the patient. The most common causes of GIB are peptic ulcer disease, aspirin-induced gastritis, variceal hemorrhage, esophagitis, neoplasms like gastric cancer. Acquired hemophilia causing acute gastrointestinal bleed is extremely rare and only a few cases are reported worldwide. Acquired hemophilia A (AHA) is a rare disorder caused by the production of autoantibodies that inactivates clotting factor VIII. We present a case of upper gastrointestinal bleed due to AHA which was undiagnosed for two years. A 74-year-old patient with a history of myasthenia gravis, presented with anemia, and GIB. She underwent multiple endoscopies without a clear bleeding source. Coagulation studies showed isolated activated partial thromboplastin time prolongation which was not corrected by mixing study. Factor VIII activity was low and Bethesda titer showed elevated inhibitor levels. Factor Eight Bypassing Agent, recombinant factor VIIa, and steroids were given to control bleeding. Her clinical condition worsened, and she passed away. Elderly patients presenting with an undiagnosed source of GIBs, inconclusive endoscopic studies should be evaluated for acquired coagulopathies, especially in those with a history of autoimmune diseases and malignancies. Prompt diagnosis and treatment are warranted as it carries a high mortality.

Review of Potential Barriers to Effective Hemostatic Management of Acquired Hemophilia A by Non-Hemophilia Experts in the United States

“…Although these delays might appear relatively short, they could still contribute to poor clinical outcomes, given that most patients presenting with AHA are elderly, have significant comorbidities, and may have life-threatening bleeds [6]. Notably, in our review, one of the patients who died was undiagnosed for two years and had previously presented with life-threatening acute gastrointestinal bleeding [22].…”

“…Four patients (17%) identified in our literature review died [15,20,22,32]. Although AHA is acknowledged to have a high mortality rate [8], there may be indications of some lack of knowledge and awareness about AHA and its optimal therapies that may have negatively affected the clinical outcome.…”

“…Twelve of the 24 articles did not discuss all recommended first-line hemostatic treatment options (Table 1), and seven of these 12 did not cite the 2009 International AHA recommendations [12][13][14][15][16][17][18]. In the subset of articles that were published after the publication of the 2017 AHA guidance [8], eight out of did not cite them [14,16,[19][20][21][22][23][24], and five of eight also did not discuss all available recommended first-line hemostatic treatment options [14,16,19,22,23]. Three out of five articles published in 2021 that could have referenced the 2020 international AHA recommendations [9] did not [18,24,25].…”

“…Four of the 24 patients (17%) in our review died: one because of suspected intracranial hemorrhage (without autopsy confirmation, so a thrombotic event was not excluded; treated with aPCC and rFVIIa) [22]; one because of pulmonary embolism possibly attributed to aPCC treatment (dose unspecified) [15]; and one because of cardiac arrest following a stroke (treated with FVIII, rFVIIa, and rpFVIII; Table 1) [20]. The fourth patient died from progressive shock with renal and hepatic failure following cardiac arrest 23 days after admission; bleeding remained uncontrolled despite treatment with 4-factor prothrombin complex concentrate, recombinant FVIII (rFVIII), and rFVIIa, and a pulmonary embolism eventually developed after two days of rFVIIa therapy (30 µg/kg), prompting a switch to plasma exchange [32].…”

“…Although AHA is acknowledged to have a high mortality rate [8], there may be indications of some lack of knowledge and awareness about AHA and its optimal therapies that may have negatively affected the clinical outcome. Clearly, there were delays in diagnosis and three [15,20,22] of four reports did not mention the dosing regimens used for bypassing agents. For example, Roy et al did not provide doses of both bypassing therapies used or specified if they were administered sequentially or concomitantly [22]; these agents have a known potential for thrombotic adverse events [38,39].…”