Age: 61.0
Sex: M
Vaccine: FLUX
Symptoms: Electrophoresis protein normal, Factor VIII deficiency, Gait disturbance, Haematoma, Haemoglobin decreased
Clinical narrative: Acquired hemophilia A; Swelling, now involving bilateral extremities and abdomen; Lupus aPTT screen positive; Hematoma; worsening ecchymoses; worsening ecchymoses; bleeding/Soft tissue bleeding; This Literature case, initially received on 28-May-2024, was reported by a health professional and concerns an adult male patient.  This literature article describes a delayed initial diagnosis of aquired hemophilia A, in a patient who initially presented to the ED with ecchymoses, soft tissue bleeding and edema.  At the time of the event the patient had Hypertension, severe Gout, Ecchymoses of his left forearm and elbow, and Edema of his left forearm and elbow. The patient had negative family and medical history of bleeding or thrombosis. Concomitant medication: colchicine for severe gout.   On an unknown date, the patient presented to the emergency department (ED) with ecchymoses and edema on his left forearm and elbow after mild trauma from bumping into a table during the previous evening. Toxicology screens were negative, and the patient's history was negative for anticoagulans and other medication. The patient's hemoglobin (Hb) was 14.3 g/dL (normal; reference interval: 12.016.0 g/dL), platelet count (PLT) of 234 k/µL (normal; reference interval: 150450 k/µL), prothrombin time (PT) of 13.0 s (normal; reference interval: 11.814.8 s (discrepantly reported as 'g/dL')), and a marked prolonged activated partial thromboplastin time (aPTT) of 70.5 s (elevated; reference interval: 23.338.6 s). The patient was otherwise stable and referred to outpatient hematology to work-up a potential coagulation disorder. However, the patient was unable to secure hematology follow-up.  Administration of company suspect drug(s): On an unknown date, the patient received Influenza virus vaccine (brand not specified) for unreported Indication, Dose, Route of administration and anatomical Location: Not reported. Lot number: Not reported. Batch number requested within follow up queries.  No additional suspect drugs.  Adverse reactions/events and outcomes: On an unknown date, one month after the first ED presentation and a week after receiving influenza vaccine, the patient presented to the ED second time with worsening ecchymoses and swelling involving bilateral extremities and abdomen. The patient's Hb dropped from 14.3 g/dL to 10.2 g/dL (depressed), aPTT remained prolonged (73.3 s; elevated), PLT (297 k/µL; normal), and PT (13.7 s; normal). After hospital admission, mixing studies demonstrated immediate inhibition, partially correcting aPTT (aPTT 1:1 mix, immediate was 53.8 s (elevated; reference range: 23.3  38.6 s)), as well as a subsequent time-dependent inhibition 1-hour post incubation (>10 s difference) (aPTT 1:1 mix incubated was 67.5 s (elevated; reference range: 23.3  38.6 s)). While a lupus aPTT screen and StaClot lupus anticoagulant (LA) (with hexagonal phospholipid neutralization) were both positive, Dilute Russell Venom Viper Time (DRVVT) screen ratio (result: 1.08, reference range: 0.8-1.2), thrombin-time, fibrinogen serum protein electrophoresis, and platelet aggregation were normal. Additional labs performed included PTT (LA sensitive) 115.7 s (elevated; reference range: 34.7-47.9 s) and PTT (LA sensitive) 1:1 mix 72.8 s (elevated; reference range: 34.7-47.9 s).   On an unknown date, as reported one day post-admission, the patient's hematoma worsened with Hb dropping to 6.6 g/dL. The patient received one unit of red blood cells and one unit of plasma. Acquired hemophilia A (AHA) was suspected based on bleeding (soft tissue bleeding) severity and time-dependent inhibitor prolongation of aPTT. The patient was subsequently administered an empiric therapy of steroids, cyclophosphamide, and 4 doses of rituximab. Antibiotic therapy was initiated to address the immunosuppression associated with these therapeutic agents. Additionally, recombinant activated Factor VII (rFVIIa) was administered every 2 hours initially, then reduced to once every 6 hours. The send-out NijmegenBethesda assay confirmed the presence of a Factor VIII (FVIII) antibody titer at 310.1 Bethesda unit per millilitre (BU/ mL) (reference interval: <0.6 U/mL). FVIII activity was undetectable at <1% (reference interval: 60%150%).   On an unknown date, as reported two weeks after admission, the patient received porcine FVIII (pFVIII), with a loading dose of 200 U/kg, maintenance doses of 100 U/kg, and tapering doses of 50 U/kg by day 3. The patient's bleeding improved with full hemostasis, decreased swelling, and improved ambulation after 3 weeks of therapy. The patient's FVIII activity improved to 36%, as well as normalization of the aPTT by day 26.  On an unknown date, reported as day 27, the patient was discharged from the hospital and continued to receive care at a tertiary hemophilia clinic.  The outcomes of all events were not reported.   Non-drug treatment/Other action taken:  Influenza virus vaccine action taken: Not Applicable Treatment medication: Cyclophosphamide, Recombinant coagulation factor viii, Rituximab  Reporter's assessment: The reporter did not provide a causality assessment for the events. The reported stated it was uncertain whether the injection exacerbated his bruising.   In conclusion, although mortality rates of AHA may reach 50%, mainly in untreated patients, the patient responded to aggressive in-hospital treatment using bypassing agents, immunosuppression, and pFVIII.  The patient's presentation and laboratory workup indicated AHA due to soft tissue bleeding, time-dependent inhibition on mixing studies, preservation of other coagulation factors, and responses to immune suppression with bypassing agents of a FVIII inhibitor. It remained unclear whether the patient had a concurrent LA with a FVIII antibody or if the FVIII antibody caused a false positive LA assay.; Reporter's Comments: Causality for swelling is unassessable based on limited information provided. Causality of haematoma is unassessable based on limited information regarding location provided, and it could also be seen as a manifestation of acquired haemophilia. Causality for acquired haemophilia, antiphospholipid antibodies positive, and soft tissue haemorrhage is assessed as not related based on biological implausibility. Causality for Ecchymosis and condition aggravated is assessed as not related to the suspect vaccine, considering that the patient already had ecchymosis at the time of the vaccination.