SESSION TITLE: Medical Students/Residents' COVID-19
SESSION TYPE: Med Student/Res Case Report
PRESENTED ON: October 18-21, 2020
INTRODUCTION: The novel Coronavirus-2019 pandemic brings a largely unfamiliar landscape and continual quest for understanding of the spectrum of presentation for this disease. Recent studies have shown endothelial injury as the trigger for the cytokine storm seen in Covid-19 infection. Hypercoagulability and excessive complement activation can lead to a diffuse thrombotic angiopathy and organ dysfunction
CASE PRESENTATION: 40 year old Hispanic male with no past medical history presented to the emergency room with weakness, AMS, recurrent hematemesis. Upon arrival, he was immediately intubated for airway protection. On exam pertinent findings included fever of 102°F, response to noxious stimuli only, and scleral icterus. Laboratory data revealed creatinine 8.08 mg/dL, LDH >2500 IU/L, haptoglobin <10 mg/dL, bilirubin 1.2 mg/dL, hemoglobin 6.8 g/dL, platelets 7,000/L with presence of 3+ schistocytes and positive test for COVID-19. PCR was negative for STEC and shigella. Given a PLASMIC score of 7, a presumptive diagnosis of thrombotic thrombocytopenic purpura (TTP) was made and daily plasma exchange (PEX) with dialysis was urgently initiated. A normal ADAMTS13 level led to discontinuation of PEX after 3 sessions; however, after 4 days hemolysis worsened with low C3 complement, therefore PEX was restarted. A complement panel was suggestive of alternative pathway dysregulation. Patient underwent 15 additional sessions of PEX with resolution of hemolysis, improved renal function and mental status.
DISCUSSION: Endothelial injury results in exposure of collagen, vWF, fibrinogen. This serves as a trigger for the hypercoagulability and TMA. TMA encompasses a group of disorders characterized by MAHA, thrombocytopenia with varying degrees of end organ damage. One subtype is TTP usually relating to endothelial dysfunction with formation of microthrombi from large platelet-vWF subunits. Another entity is hemolytic uremic syndrome, which is characterized by excessive complement activation often caused by shigella-toxin. Neither of which were seen in this patient. We suspect this patient’s presentation to be a manifestation of complement mediated TMA (CM-TMA) due to COVID. Previous review articles propose the possibility of viral infections including H1N1 causing dysregulation of complement cascade leading to TMA. Autoantibodies can form to complements that regulate complement cascade such as Factor H or Membrane Cofactor Protein. This can lead to dysregulation leading to C3 consumption, endothelial damage and formation of platelet microthrombi. His improvement with PEX poses a probable mechanism of removing cytokines, activated complements and antibodies.
CONCLUSIONS: Complement mediated thrombotic microangiopathy could be the final pathway in critical illness. Our case shows that PEX may provide therapeutic benefit by normalization of the complement pathway while awaiting clearance of COVID viremia.
Reference #1: Lopes R. Viral-associated thrombotic microangiopathies. Hematol Oncol Stem Cell Ther. 2011;4:51-9.
Reference #2: Bitzan M, Zieg J. Influenza-associated thrombotic microangiopathies. Pediatr Nephrol. 2018;33:2009-25.
Reference #3: Magro C, Mulvey J, Berlin D, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases. Transl Res. 2020;S1931 5244(20)30070-0.
DISCLOSURES: No relevant relationships by Usha Anand, source=Web Response
No relevant relationships by John French, source=Web Response
No relevant relationships by Mehrin Jawaid, source=Web Response
No relevant relationships by Danielle Logan, source=Web Response
No relevant relationships by Vijay Nath, source=Web Response