SARS-CoV-2 and pulmonary embolism: who stole the platelets?

Abstract

Background: Patients infected with SARS-CoV-2 often develop venous and arterial thrombosis. The high patient mortality is partly attributed to thrombotic events. An emerging trend is the presence of immunological phenomena including antiphospholipid antibodies which may promote thrombosis. The mechanism for these observations is not clear though many patients with SARS-CoV-2 develop thrombocytopenia. Case presentation: We describe a patient with SARS-CoV-2 pneumonitis who presented with intermediate risk pulmonary embolism (PE). Careful attention to his daily platelet count suggested the possibility of immune mediated heparin-induced thrombocytopenia (HIT) which was confirmed by laboratory testing and resolved when anticoagulation was switched to a direct thrombin inhibitor. Conclusions: Since excessive platelet activation and in situ thrombosis occur in HIT, this case underscores the need to consider that thrombocytopenia in patients with SARS-CoV-2-most of whom receive heparinoids-may be unrecognized HIT. A central role for the platelet in the etiology of thrombosis during the COVID-19 pandemic should be explored.

COVID-19 and Cardiovascular Disease

“… 163 , 164 Implicating adaptive immune system dysfunction, antiplatelet, antiphospholipid, and antiendothelial cell autoantibodies have been demonstrated in patients with SARS-CoV-2. 165 – 168 Prothrombotic autoantibodies targeting phospholipids and phospholipid binding proteins (aPL antibodies) were found in 52% of 172 hospitalized patients with COVID-19 169 and included anticardiolipin IgG, IgM, and IgA; anti-B2 glycoprotein I IgG, IgM, and IgA; and antiphosphatidylserine/prothrombin (aPS/PT) IgG and IgM. Antiphospholipid antibodies also activated neutrophils and initiated neutrophil extracellular trap extrusion, consistent with the proposed immunothrombosis mechanism in COVID19.…”

“…Antiphospholipid antibodies also activated neutrophils and initiated neutrophil extracellular trap extrusion, consistent with the proposed immunothrombosis mechanism in COVID19. 170 Early case reports indicated thrombocytopenia in some patients with COVID-19 may be caused by easier haptenization of platelet antigens, including the cytokine CLCL4, also known as PF4 (platelet factor 4), as evidenced by circulating anti-PF4 antibodies 165 , 171 and earlier observations in which light transmission aggregometry functional assays with the additional of heparin to donor platelets mixed with serum from patients with COVID-19 promoted platelet activations. 165 These observations present a true treatment dilemma, given the propensity of patients with COVID-19 to form thrombi, and the need for anticoagulation.…”

“… 170 Early case reports indicated thrombocytopenia in some patients with COVID-19 may be caused by easier haptenization of platelet antigens, including the cytokine CLCL4, also known as PF4 (platelet factor 4), as evidenced by circulating anti-PF4 antibodies 165 , 171 and earlier observations in which light transmission aggregometry functional assays with the additional of heparin to donor platelets mixed with serum from patients with COVID-19 promoted platelet activations. 165 These observations present a true treatment dilemma, given the propensity of patients with COVID-19 to form thrombi, and the need for anticoagulation. Curiously, several patients with COVID-19, meeting clinical diagnostic criteria for heparin-induced thrombocytopenia, subsequently tested positive for anti-PF4 antibodies, but in heparin-induced platelet aggregation assays were negative using the heparin-induced thrombocytopenia confirmatory test platelet serotonin release assay.…”

Heparin-induced thrombocytopenia in patients with COVID-19: a systematic review and meta-analysis

“…Of these, 1,986 were excluded, and 22 full texts were screened for eligibility. Eventually, 15 studies [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] met the eligibility criteria and were included in qualitative synthesis, and 7 studies 29,[32][33][34][35][36]40 were sufficient for quantitative synthesis. Of 7 studies eligible for meta-analysis, the risks of bias were individually assessed.…”

Contrast between Prevalence of HIT Antibodies and Confirmed HIT in Hospitalized COVID-19 Patients: A Prospective Study with Clinical Implications

“…To date, HIT data in SARS-CoV-2-infected patients are scarce, limited to the report of a few HIT cases confirmed using platelet activation assay, and HIT-associated antibody prevalence remains poorly investigated. [3][4][5][6][7][8][9][10][11][12][13] Our prospective cohort study aimed to characterize patients with clinical suspicion of HIT and determine HIT-associated antibody prevalence in hospitalized SARS-CoV-2-infected patients. This study was part of the ICU-COVID and French-COVID cohort registries approved by our institutional ethics committee (IDRCB, 2020-A00256-33; CPP, 11-202020.02.04.68737).…”