UNCORRECTABLE AUTOIMMUNE FACTOR VIII DEFICIENCY IN PROTHROMBOTIC SETTING IN A PATIENT WITH ADVANCED LUNG DISEASE

Abstract

TYPE: Case Report TOPIC: Lung Pathology INTRODUCTION: Fibrotic lung diseases are associated with systemic hypercoagulability and elevated levels of factor VIII (FVIII). Autoantibodies against coagulation factors have been reported in patients with autoimmune disease. We report uncorrectable FVIII deficiency in a patient with advanced nonspecific interstitial pneumonia (NSIP). CASE PRESENTATION: A 54-year-old man with NSIP, referred to us for lung transplant (LTx) evaluation in December 2020, had elevated platelets (646,000/μL), D-dimer (2139 ng/mL), factor-V activity (174%), fibrinogen (569 mg/dL), and partial thromboplastin time (>150 seconds). Mixing studies suggested high FVIII inhibition with decreasing inhibitor titer of 485, 80.5, and 1.8 Bethesda units from January to March 2021, and FVIII activity <1%. Activity of factors IX-XII, von Willebrand factor, anti-thrombin-III, protein C, and protein S were normal. Connective tissue disease (CTD) serology was consistent with systemic lupus erythematosus and anti-synthetase syndrome. His IgG1 and IgG3 levels were elevated (1610 mg/dL and 143 mg/dL, respectively). There was no clear evidence of bleeding; deep venous thrombosis and pulmonary embolism evaluations were negative. Despite receiving FVIII replacement therapy, immunoglobulin, mycophenolate mofetil, rituximab, cyclosporine, and corticosteroids, his FVIII level remained critically low, and he was not considered an LTx candidate. DISCUSSION: Acquired FVIII deficiency is mediated by inhibitor polyclonal IgG antibodies and is often associated with CTD. Treatment involves FVIII replacement and immunosuppression. Our patient had uncorrected, possibly autoimmune FVIII deficiency, which is an absolute contraindication for LTx. CONCLUSIONS: This is the first report of uncorrectable autoimmune FVIII deficiency in the setting of systemic hypercoagulability in a patient with NSIP. DISCLOSURE: Nothing to declare. KEYWORD: AUTOIMMUNE FACTOR VIII DEFICIENCY