Case Presentation: This is a unique case of acquired thrombotic thrombocytic purpura (aTTP) due to the novel SARS-CoV-2 virus (COVID-19). Our patient is a 36-year old male with hypertension, alpha-thalassemia trait, who presented with abdominal pain. He has a family history pertinent for a sister with immune thrombocytopenic purpura. He was found to have cholecystitis and was treated with antibiotics and an endoscopic retrograde cholangiopancreatography with biliary stent placement. At admission, his initial CBC showed hemoglobin 11.2 g/dL and a platelet count of 209,000 platelets per mcL, elevated liver enzymes, and a total bilirubin of 4.8 mg/dL. On COVID-19 screening, he was found to have COVID-19 IgG antibodies but negative on COVID PCR testing. He had no recollection of COVID-19 symptoms previously. On day two of admission, the patient’s platelet counts acutely dropped to 45 K/uL and his total bilirubin increased to 20.8 mg/dL, with a direct bilirubin count of 14.1 mg/dL. Labs were notable for lactate dehydrogenase of 908 U/L and haptoglobin < 20 g/L. His platelet count dropped further to 19 K/uL. His ADAMTS13 Ab was found to be elevated at 62 U/ml and activity level <2%, consistent with aTTP. Peripheral smear revealed 8-9 schistocytes per hpf. The patient was treated with plasma exchange therapy for five days and 1 gm of Solumedrol once a day for three days followed by a prednisone taper. He was discharged ten days later with platelet count of 498 K/uL and weekly Rituximab for four weeks.
Discussion: aTTP is a life-threatening thrombotic microangiopathy (TMA) caused by reduced platelet adhesion and aggregation. ADAMTS13 is a proteinase enzyme that cleaves the ultra-large Von Willebrand factor (ULVWF). When levels of ADAMTS13 are low, ULVWF is not cleaved, leading to ULVWF-platelet aggregation and consumption and destruction of platelets, which can also shear red blood cells, causing anemia, end-organ damage and ultimately death. Several reports demonstrate that COVID-19 could lead to autoimmune and auto-inflammatory conditions.[1] Molecular mimicry by infectious diseases has long been identified as a trigger for autoimmune disease. However, a second proposed pathogenesis is that pro-inflammatory and dysregulated immune response onset by COVID-19 may cause environmental insults to predisposed individuals. Although the pathogenesis of aTTP is unknown, often viral etiologies have been the cited culprits due to the development of autoantibodies to the ADAMTS13 enzyme. Investigating this link through genome-wide studies may provide insights into this connection.So far there are three COVID-19-induced aTTP cases that have been reported.[2-4] One case had an active COVID-19 infection and two cases had negative COVID-19 tests for active infection and positive COVID-19 IgG Ab, similar to our patient. All cases improved with treatment for TTP.
Conclusions: This abstract uniquely describes a case of aTTP triggered by COVID-19 in a patient who was likely predisposed to autoimmune hematologic conditions based on family history. COVID-19 is increasingly recognized as a cause for long-term sequelae after the acute viral infection has been resolved. aTTP has largely been attributed to an autoantibody to ADAMTS13 but may now be recognized as triggered after COVID-19, as in our patient and other case reports. Further investigation into this association and its possible mechanisms are important for the early treatment of this deadly disease.