A Case Series of Acquired Factor Inhibitor Following Sars-COV2-Vaccination

Abstract : Autoimmune disorders post viral illness and post vaccination are some of the known complications. COVID 19 is known to cause complement dysregulation and possible reactivation of known autoimmune disorders. New data are emerging on the possible autoimmune reactivation and cases of de novo ITP and vaccine induced immune thrombotic thrombocytopenia are reported. We are presenting two cases of factor deficiencies due to acquired factor inhibitor in patients who had no apparent cause but who had recently received the Moderna COVID-19 vaccine. We hypothesize that just like native COVID 19 infection can be associated with development of acquired inhibitors, so can the COVID 19 vaccination.

Cases:An 83 year old Caucasian Male with history of Arrhythmia, Coronary artery disease, H/O heart artery stent and hypertension, had received the second dose of Moderna covid vaccine one month prior to presentation. Presented with new onset headache and noted to have large right sub insular acute intra parenchymal hemorrhage. He was managed conservatively, and this bleed was attributed to his h/o hypertension. Post treatment was discharged to rehab, where he had worsening neurological status and repeat imaging showed slightly expanded size of a parenchymal hemorrhage centered in the right sub insular region and increasing surrounding edema with new tiny right frontal cortical parenchymal hemorrhage. Initial admission labs reveled a prolonged APTT of 70 and PT normal after his readmission from rehab, his PTT remained elevated to 70 and PT became prolonged to 17. PT. APTT mixing studies demonstrated only partial correction of PT and no correction of APTT. All factor levels were normal except Factor IX low at 8% and Factor XI low at 2.4%. Bethesda titer was positive at 11 BU to specific to factor IX. Further work up demonstrated no oncologic or rheumatological etiology for the coagulation inhibitor. The only possible etiology had been his age and patient had received SARS COV2 moderna vaccine. The patient was treated with rituximab, prednisone and cyclophosphamide with improvement in the inhibitor titer.

A 77-year-old Caucasian female with history of hypertension, obesity, steroid induced psychosis, and Moderna Covid-19 vaccination four months prior. She presented to the hospital with epigastric pain, hematochezia, hematuria, epistaxis, and significant bruising without trauma. Laboratory studies showed hemoglobin drop from baseline of 13.8 to 11.8 to 8.2 g/dL. Significant coagulopathy, with elevated PT 130 sec, PTT 108.7. All factor levels were normal except Factor X levels low at <2%. Mixing study of the prolonged prothrombin time mainly demonstrates an inhibitory pattern, with incomplete correction. (1:1 mix PT 22.7 sec; normal 9.4-12.5 sec). Bethesda titers could not be demonstrated. No neoplastic or rheumatologic etiology of her inhibitor was found. She was given cryoprecipitate and vitamin K with no improvement in her coagulation studies. She received factor X infusion for 3 doses 2500 units during day 3 of her hospitalization. She was treated with prednisone and weekly rituximab with complete normalization of her Factor X levels at 132%.

Discussion:Acquired inhibitors to coagulation factors are rare disorders that can be related to infections, malignancy, autoimmune conditions, and pregnancy and sometimes seen spontaneously in older individuals. There have been several individual case reports of acquired coagulation inhibitors with COVID 19 infection including inhibitors to III, Factor XI, Factor V and Thrombin. To our knowledge there have been no acquired inhibitors described to the COVID vaccine however, it would seem conceptually possible. Acquired factor deficiencies should be suspected when a patient presents with no previous history of bleeding, use of anticoagulation and unexplained prolonged prothrombin, and activated partial thromboplastin time. It is vital to have high index of suspicious for prompt recognition as it can have a high mortality. Treatment would involve resuscitation and eradicating the inhibitor with immunosuppression. It would be interesting to follow this patient long term for any relapse. In the above mentioned cases, no other etiologies could be attributed to the abnormal coagulopathy and could be related to the SARS-COV-2 vaccine.