Acquired hemophilia A following wasp stings: a case report

Acquired hemophilia A is a rare acquired bleeding disorder caused by autoantibodies against factor VIII (FVIII).^[1] Wasp stings can cause local inflammation, allergic reactions, and even multiple organ dysfunction. Acquired hemophilia A secondary to a wasp sting is rare and may lead to missed diagnosis or delayed treatment. We report a case of acquired hemophilia A secondary to a wasp sting in a 61-year-old man.

A 61-year-old man with progressive ecchymosis was referred to our hospital with left thigh swelling and pain for 10 d after a wasp sting. He developed left thigh pain and swelling 1 d after the sting. Topical treatment was ineffective, and the symptoms gradually worsened. On day 6 after the sting, computed tomography (CT) and magnetic resonance imaging at a local hospital suggested a lower-limb hematoma. Hematoma aspiration and left lower-limb arterial embolization were performed. After these procedures, the swelling and pain worsened, and the ecchymosis extended to the left lower limb.

The patient was previously healthy and had no history of hypertension, diabetes, or other chronic diseases. He had no personal or family history of bleeding disorders and had no recent exposure to anticoagulants, antiplatelet agents, or immunomodulatory drugs. His vital signs were stable. Physical examination showed marked swelling and extensive ecchymosis of the left lower limb, with tense and tender skin and limited movement. A healed punctured sting wound was noted over the medial malleolus of the right lower limb. The left dorsalis pedis pulse was palpable, and distal sensation and motor function were preserved.

Laboratory tests showed a red blood cell count of 2.12×10¹²/L, hemoglobin 67 g/L, and white blood cell count 11.6×10⁹/L. Coagulation tests showed FVIII activity 0.20%, FVIII inhibitor 4.8 BU, activated partial thromboplastin time (APTT) 82.20 s, prothrombin time 12.40 s, international normalized ratio 1.00, fibrinogen 6.38 g/L, fibrin/fibrinogen degradation products 7.40 mg/L, and D-dimer of 0.51 mg/L. The total bilirubin concentration was 24.1 μmol/L, and the direct bilirubin concentration was 9.0 μmol/L. The CT of the left lower limb showed swelling of the anterolateral thigh muscles with local hematoma formation. Tests for lupus anticoagulant, antinuclear antibodies, vasculitis-related antibodies, and tumor markers were negative.

A mixing study was not performed in this case, which was a limitation of the diagnostic workup. Nevertheless, the absence of a previous bleeding history, delayed progressive soft-tissue bleeding after wasp sting, isolated APTT prolongation, markedly reduced FVIII activity, and a positive FVIII inhibitor supported the diagnosis of acquired hemophilia A after hematology consultation.

He received hemostatic therapy with FVIII concentrates, prothrombin complex concentrates, and recombinant activated factor VII, followed by prednisone and cyclophosphamide after confirmation of the FVIII inhibitor. On day 13 after treatment, the swelling and pain of the left lower limb improved markedly, and the ecchymosis gradually resolved. He was discharged with continued oral immunosuppressive therapy. At the 2-week follow-up, the FVIII activity was 2.0%, and the FVIII inhibitor was 4 BU. The swelling and pain disappeared, and the patient resumed normal activity.

Acquired hemophilia A occurs more often in older adults and may be associated with autoimmune disease, malignancy, pregnancy, infection, or drug exposure, although approximately half of cases have no identifiable trigger.^[2] Typical manifestations include new-onset subcutaneous, muscular, mucosal, or postoperative bleeding in patients without a previous bleeding history. Laboratory findings usually include isolated APTT prolongation, reduced FVIII activity, and a positive FVIII inhibitor.^[1]

Wasp venom can affect the coagulation system. Previous studies have shown that bee or wasp venom may disturb hemostasis through phospholipase activity, protease activity, anticoagulant effects, fibrinogenolysis, and heparin-like coagulopathy.^[3-6] These changes mainly reflect direct venom toxicity or systemic toxicity reactions and may be accompanied by PT or APTT prolongation, hyperfibrinolysis, reduced fibrinogen levels, elevated D-dimer levels, or multiple organ injury. In contrast, this patient presented mainly with severe soft-tissue bleeding and an isolated intrinsic pathway abnormality. His INR was normal, fibrinogen was not reduced, D-dimer was only mildly elevated, and most importantly, FVIII activity was extremely low when a measurable FVIII inhibitor was used. These findings suggest that the bleeding was not simply caused by venom-induced factor consumption or fibrinolysis but was more consistent with autoimmune bleeding mediated by an acquired FVIII inhibitor.

A causal mechanism between wasp sting and acquired hemophilia A cannot be established from a single case. Bee venom phospholipase A2 can induce type 2 immune and antibody responses through the IL-33/ST2 pathway.^[7] Local tissue injury and venom-related immune activation may therefore disrupt immune tolerance to FVIII in a susceptible host. The gradual progression of bleeding after the sting was compatible with a delayed immune response, although causality remains unproven.

In conclusion, delayed progressive hematoma after wasp sting should not be attributed only to local venom toxicity, vascular injury, or toxic coagulopathy. Although a mixing study was not performed in this case, similar patients should undergo early mixing studies, coagulation factor activity testing, and inhibitor assays to avoid unnecessary punctures, surgeries, or interventional procedures and to allow timely hemostatic and immunosuppressive treatment.

Funding: This case report did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Ethical approval: Ethical approval was not required for this case report. Written informed consent for publication was obtained from the patient.

Conflicts of interest: The authors declare that they have no conflicts of interest.

Contributors: LD: conceptualization, data curation, writing - original draft; YZ: supervision, writing - review & editing; FZ: investigation (as the attending physician), clinical management; JW: methodology, validation; XML: supervision, project administration, writing - review & editing. All authors have read and approved the final manuscript.