REFRACTORY THROMBOTIC THROMBOCYTOPENIC PURPURA DUE TO COVID-19

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Thrombotic Thrombocytopenic Purpura (TTP) is a hematologic emergency with a mortality of 90% if left untreated. Its is formerly characterized by a pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia (MAHA), acute kidney injury (AKI), and neurologic deficits. These were classic before the routine use of therapeutic plasma exchange (PEX) because the majority of patients developed progressive thrombotic microangiopathy(TMA) and died from untreated disease. There are multiple etiologies associated with TTP and among those rarely reported is COVID-19. SARS-CoV-2 can result in the production of platelet-rich microthrombi and decrease the level of ADAMTS13. This can precipitate TMA and rarely result in TTP. CASE PRESENTATION: A 44-year-old African-American Female with no medical history presented to our facility complaining of vomiting and diarrhea associated with bleeding gums and easy bruising. On presentation, she was calm with stable vital signs. On physical exam, she had scleral icterus and conjunctival pallor associated with petechial rash and localized ecchymosis. Initial labs were remarkable for anemia(8.6g/dL), severe thrombocytopenia(3x103/µL), AKI(creatinine 1.70mg/dL), elevated lactate-dehydrogenase(1297Units/L), and high D-dimer(636ng/mLDDU). Hemolysis workup revealed MAHA and schistocytes were confirmed on blood smear. The PCR for COVID-19 was positive. All stool studies and other workup was unremarkable. Her PLASMIC score was 6 indicating high risk for severe ADAMTS13 deficiency, and therefore she was immediately admitted to the ICU and started on steroids, rituximab, and PEX. After 5-days of PEX, her platelet count improved to 199x103/µL and was deemed responsive to initial therapy. The following day the platelet count dropped to 8x103/µL and the patient was restarted on PEX. She failed to improve despite appropriate therapy and the disease was deemed to be refractory. A multidisciplinary decision was made to initiate Caplacizumab. She completed a total of 17 PEX sessions and significant improvement in her clinical course was achieved. She was eventually discharged home in stable condition on a tapered course of steroids. DISCUSSION: When ADAMTS13 is deficient, von Willebrand factor multimers accumulate and increase platelet aggregation causing TTP. Since its activity testing has a prolonged turnaround time, the PLASMIC score is validated to identify patients at risk for severe ADAMTS13 deficiency and facilitate timely management. Our patient ADAMTS13 activity was 2.2% correlating with a severe deficiency. PEX is associated with a significant decline in mortality as it replaces the deficient ADAMTS13 and removes the inhibitory autoantibodies from the circulatory system. CONCLUSIONS: TTP is a hematologic emergency that requires prompt therapy. It's important to include COVID-19 as a potential etiology and to explore other therapeutic approaches for a refractory TTP. REFERENCE #1: Sayani, F. A., & Abrams, C. S. (2015). How I treat refractory thrombotic thrombocytopenic purpura. Blood, 125(25), 3860–3867 REFERENCE #2: Bendapudi PK, Hurwitz S, Fry A, et al. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol 2017; 4:e157. REFERENCE #3: Sweeney, J. M., Barouqa, M., Krause, G. J., Gonzalez-Lugo, J. D., Rahman, S., & Gil, M. R. (2021). Low ADAMTS13 Activity Correlates with Increased Mortality in COVID-19 Patients. TH open : companion journal to thrombosis and haemostasis, 5(1), e89–e103 DISCLOSURES: No relevant relationships by Joel Brooks, source=Web Response No relevant relationships by Ruben Cabrera, source=Web Response No relevant relationships by Jorge Cruz, source=Web Response No relevant relationships by Nathalie De paz, source=Web Response No relevant relationships by Tarig Elhakim, source=Web Response No relevant relationships by Jose Gascon, source=Web Response No relevant relationships by Daniel Gonzalez, source=Web Response No relevant relationships by Carlos Guida, source=Web Response No relevant relationships by Robert Hernandez, source=Web Response No relevant relationships by Ilde Lee, source=Web Response No relevant relationships by Daniel Zapata, source=Web Response