• Association of Acquired Factor VIII Deficiency with COVID-19
  • Mohammad Shayestehpour,1,*
    1. Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, I.R. Iran


  • Introduction: Acquired factor VIII (FVIII) deficiency, or acquired hemophilia A (AHA), is a rare autoimmune disease characterized by severe bleeding. Severe acute respiratory syndrome coronavirus 2 (SARS CoV 2) is a novel viral agent that can cause a life-treating respiratory disorder named coronavirus disease 2019 (COVID 19). We present here a case of acquired factor VIII deficiency associated with COVID-19.
  • Methods: A 34-year-old woman with abnormal uterine bleeding was referred to the hospital ten days after cesarean delivery. Platelet count (PLT), prothrombin time (PT), partial thromboplastin time (PTT) tests were in the normal ranges, but the hemoglobin (Hb) level was reduced to 7 g/dL. Administration of Fresh-Frozen Plasma (FFP), packed cell (P.C), and recombinant factor VII could not control bleeding. She was discharged and returned to the hospital nine days later with symptoms of fever, bleeding, and respiratory failure. The patient underwent hysterectomy, discharged and returned to the hospital nine days later with symptoms of fever, bleeding, and respiratory failure.
  • Results: She was intubated, and had a heart rate of 110 per min and blood pressure of 100/70. The patient's body temperature was 38℃ and antibiotics (vancomycin and meropenem) were started. She had Hb level of 6.5 g/dL, PLT of 150000/mm3, and PTT of 75 s. Polychromasia was observed in the patient's peripheral blood smear (PBS) while blast cells and schistocytes were not seen. Hemoperitoneum detected on sonography, and abdominal angiography was normal. The patient underwent laparotomy and splenectomy. Administration of FFP and P.C increased PTT to the normal range, Hb to 9 g/dL and decreased the bleeding. SARS-CoV-2 was detected in the patient's sample by reverse-transcription polymerase chain reaction test (RT-PCR), although she had a normal chest CT. The sedimentation rate (ESR) and level of C-reactive protein (CRP) were normal and lymphopenia was not happened. The patient was discharged with good general condition and PPT of 45 s without receiving any treatment for COVID-19. She was readmitted to the hospital 4 days later, that result of laboratory tests as fallow: White Blood Cells (WBC) 23000/mm3, PLT 450000/mm3, lactate dehydrogenase (LDH) 700 U/L, Hb 5.8 g/dL, PT 14s, PTT 95s. In PTT mixing study, PTT decreased to 50s without incubation time and to 73s after 3h incubation in 37℃. In PT mixing study, PT was 12.9s immediately after mixing test, and it increased to 17s, 3h after incubation. The sonography showed a hematoma with 500 cc of blood (diameter of 10 cm) in the hypogastric region. In addition, a hematoma with diameter of the 13 cm was observed near to the gastric. After administration of P.C (one unit), FFP, recombinant factor VII, IVIG (34g daily for 5 days), dexamethasone (24mg/day), vancomycin and meropenem the following laboratory data were obtained: Hb 8.2 g/dL, PTT 41s, INR 1.43 and WBC 22100/mm3. Anti-factor VIII antibodies were detected in serum (180 BU) and level of factor VIII was 1%. Treatment with cyclophosphamide (100mg bidaily) was initiated. The patients under treatment with dexamethasone and cyclophosphamide had a PTT ranged from 50 to 70 s without bleeding. In final sonography, the diameter of hematoma was decreased. The patient was discharged on 75 mg of prednisone daily and 100mg of cyclophosphamide bidaily. She had not fever and had Hb of 11 g/dL and PTT of 71s. Anti-factor VIII antibodies were undetectable and factor VIII activity was normal.
  • Conclusion: Infection with SARS-CoV-2 can be associated with an acquired factor VIII (FVIII) deficiency in human. Performing PTT mixing test in cases of COVID-19 with a prolonged PPT and unexplained bleeding is recommended.
  • Keywords: Coagulation, Factor VIII, COVID-19, Hemophilia A