Pulmonary Embolism in Acquired Hemophilia A: A Rare Complication With Factor VIII Inhibitor Bypassing Activity Therapy

Abstract

Acquired hemophilia A (AHA) is an uncommon complication caused by autoantibodies against Factor VIII. The main concern with these patients is hemorrhage, which is often treated with Factor VIII inhibitor bypassing activity (FEIBA). On rare occasions, treatment with FEIBA can result in thromboembolism, a potentially fatal complication. This unfortunate situation occurred in our patient, a 64-year-old female who was treated with FEIBA after being diagnosed with AHA. After initiating FEIBA, she developed clinical signs and symptoms of pulmonary embolism, which was ultimately responsible for her acute death. While pulmonary embolism may be a rare complication of FEIBA treatment, clinicians should be aware of its possibility, especially as the complete safety profile for this treatment is not well known.

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

“…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.…”

“…Fifteen of the 24 studies did not reference the 2009 international AHA recommendations (Table 1) [11]. 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].…”

“…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].…”

“…In many of the identified articles, physicians might have been unaware of all available hemostatic treatment options (especially the availability of rpFVIII) or unclear of how they should be dosed [15]. In 2017, Kruse-Jarres et al provided comprehensive guidance for the management of AHA, including recommended first-line hemostatic treatments and dosing regimens [8].…”

“…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].…”