Sex: M
Vaccine: COVID19
Symptoms: Haemoglobin, International normalised ratio, Investigation, Physical examination, Platelet count
Clinical narrative: Acquired Hemophilia A; This is a literature report.  Authors present a case of acquired hemophilia A (AHA) after application of Pfizer-BioNTech SARS-CoV-2 vaccine. The patient, a 67-year-old male with a history of hypertension and asymptomatic pulmonary sarcoidosis not receiving any pharmacological treatment, began to experience left thigh tightness and cramping pain at day + 19 after his second dose of the Pfizer-BioNTech COVID-19 vaccine. He originally presented to the emergency department (ED), where an ultrasound was performed, which was negative for deep venous thrombosis. He was instructed to follow up with his sarcoidosis clinic and was discharged from the ED. However, two days later, he presented to another ED for worsening pain and persistent swelling of his left thigh. He was found to have a large hematoma of his left posterior leg extending from his buttock to below his left knee. A smaller area of ecchymosis was also noted on his right arm proximal to the medial epicondyle. Physical exam was otherwise unremarkable. His activated partial thromboplastin time (aPTT) was 72 seconds (normal 25-35 seconds). Reviewof prior medical records showed normal aPTT in 2013 and 2014, but no more recent coagulation laboratories. He was transferred to Hospital for further evaluation. His hemoglobin level was 10.2 g/dL (from 11.4 g/dL 2 days prior and down from a baseline of 15.5 g/dL in September 2020). A 1:1mixing study combining the patient's plasma (aPTT of 78 seconds) with a normal control plasma (aPTT of 28 seconds) showed no significant correction of the aPTT (i.e., 60 seconds), suggesting the presence of an inhibitor other than factor deficiency. Factor VIII activity was undetectable (i.e., <1%) and an inhibitor assay confirmed the presence of a factor VIII inhibitor at 110 Bethesda Units/mL. Other laboratories were significant for: platelets 207,000/mm3, white blood cells 9,740/mm3, prothrombin time 13 seconds (international normalized ratio: 0.99), creatinine 1.27 mg/dL (estimated glomerular filtration rate>60mL/min), blood urea nitrogen 19 mg/dL, aspartate aminotransferase 16 U/L, alanine aminotransferase 19 U/L, total bilirubin 0.6 mg/dL. A computed tomography with intravenous contrast of the chest/abdomen/pelvis from 7 months before presentation showed stable calcified mediastinal and bilateral hilar lymph nodes, without any signs of malignancy. Patient had a colonoscopy in 2017 without any signs of malignancy. Last prostate specific antigen was 0.44 ng/mL and patient did not report any urinary symptoms. They also obtained antinuclear antibodies, ds-DNA antibodies, and rheumatoid factor, which were negative. The patient was started on factor eight inhibitor bypass activity (FEIBA) 4,500 u/kg every 8 hours, oral prednisone 1mg/kg daily (i.e., 90mg daily), and rituximab therapy (375 mg/m2 weekly for 4 doses). Due to continued hemoglobin drop over the first few days of hospitalization, recombinant factor VIIa was also initiated. Seven days after the first dose of rituximab, factor VIII inhibitor decreased to 59 Bethesda Units/mL, but aPTT persisted in the 70s. Finally, after another 7 days and before the third dose of rituximab, factor VIII inhibitor was 8 Bethesda Units/mL and FEIBA was stopped. Patient completed four doses of rituximab and a 28-day taper of prednisone after discharge. Factor VIII activity was at 171% with undetectable factor VIII inhibitor at day +34 after admission. No new signs of bleeding have been observed after completion of all treatments. AHA is a rare autoimmune disorder characterized by autoantibody formation against clotting factor VIII, resulting in disruption of secondary hemostasis. Most cases of AHA in nonpregnant and nonpostpartum patients are associated with pre-existing autoimmune conditions or malignancy. However, this patient had no evidence of malignancy and no pre-existing autoimmune disorders, except for sarcoidosis. No reports of an association between pulmonary sarcoidosis and AHA were found on literature review. While certain medications can be associated with AHA, the patient's medications included only amlodipine, benazepril, pantoprazole, and rizatriptan, none of which have been associated with AHA. The only identified risk factor for the development of AHA, based on the suspicious timing, was the Pfizer-BioNTech SARS-CoV-2 vaccine. While the causal relationship cannot be proven, authors still felt compelled to report this case to increase awareness among health care providers about potential adverse events after COVID-19 vaccination. Whether the course of AHA after COVID-19 vaccine is similar to regular AHA is also unknown. Unlike prior reports of post-COVID-19 vaccine AHA, the patient had persistence of aPTT elevation with significant hemoglobin drop, requiring a multi-strategy approach with FEIBA, recombinant factor VIIa, glucocorticoids, and rituximab. As we learn more about COVID-19 and the effects of its vaccine, there is an urgent need to report cases like this one, to share experiences, and help us battle this pandemic.; Sender's Comments: As there is limited information in the case provided, the causal association between the event and the suspect drug cannot be excluded. The case will be reassessed once new information is available. The impact of this report on the benefit/risk profile of the Pfizer drug is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committees, and Investigators, as appropriate.