Immune Thrombocytopenia Secondary to COVID-19: a Systematic Review

Abstract

Immune thrombocytopenia, often known as immune thrombocytopenic purpura (ITP), has emerged as an important complication of COVID-19. A systematic review was done to analyze the clinical profile and outcomes in a total of 45 cases of new-onset ITP in COVID-19 patients described in literature until date. A comprehensive approach is essential for diagnosing COVID-19-associated ITP after excluding several concomitant factors that can cause thrombocytopenia in COVID-19. Majority of ITP cases (71%) were found to be elderly (> 50 years) and 75% cases had moderate-to-severe COVID-19. Three patients (7%) were in the pediatric age group. Reports of ITP in asymptomatic COVID-19 patients (7%) underscore the need for COVID-19 testing in newly diagnosed patients with ITP irrespective of COVID-19 symptoms amid this pandemic. ITP onset occurred in 20% cases 3 weeks after onset of COVID-19 symptoms, with many reports after clinical recovery. SARS-CoV-2-mediated immune thrombocytopenia can be attributed to the underlying immune dysregulation, susceptibility mutations in SOCS 1, and other mechanisms, including molecular mimicry, cryptic antigen expression, and epitope spreading. No bleeding manifestations were reported in 31% cases at diagnosis. Severe life-threatening bleeding was uncommon. One case of mortality was attributed to intracranial hemorrhage. Secondary Evans syndrome was diagnosed in one case. Good initial response to short course of glucocorticoids and intravenous immunoglobulin has been found with the exception of delayed lag response in one case. Thrombopoietin receptor agonist usage as a second-line agent has been noted in few cases for short duration with no adverse events. In the relatively short follow-up period, four relapses of ITP were found.

Keywords: Bleeding; COVID-19; Hematological complication; ITP; Low platelet; Purpura.

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Diagnostic approach to COVID-19-associated immune thrombocytopenia. DIC, disseminated intravascular coagulation; HLH, hemophagocytic lymphohistiocytosis; TTP, thrombotic thrombocytopenic purpura; PT, prothrombin time; APTT, activated partial thromboplastin time; ADAMTS-13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13; PF4, platelet factor 4; DITP, drug-induced thrombocytopenia; HbsAg, hepatitis B surface antigen; HCV, hepatitis C virus; HIV, human immunodeficiency virus; CMV, cytomegalovirus; EBV, Epstein-Barr virus; VZV, varicella zoster virus; H. pylori, Helicobacter pylori; ANA, anti-nuclear antibody; ANCA, anti-neutrophil cytoplasmic antibody; ACLA, anti-cardiolipin antibody; MM, multiple myeloma; SPEP, serum protein electrophoresis; MAIPA, monoclonal antibody–specific immobilization of platelet antigen; IVIG, intravenous immunoglobulin; TP-RA, thrombopoietin receptor agonists