Is COVID-19 an Independent Risk Factor for Heparin-Induced Thrombocytopenia?

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a viral respiratory illness initially described in Wuhan, China, and was declared a pandemic by World Health Organization (WHO) in 2020, and the disease is named coronavirus disease (COVID-19). SARS-CoV2 is known to cause fever, cough, fatigue, and acute respiratory distress syndrome. As more patients become infected, extrapulmonary manifestations came to rise and hypercoagulability is one among those. COVID-19 could predispose patients to both venous and arterial thromboembolic events which are commonly treated with unfractionated heparin or low molecular weight heparin (LMWH). The treatment of patients who develop heparin-induced thrombocytopenia (HIT) while being treated with heparin or LMWH for COVID-induced thromboembolic complications is challenging. We describe a patient admitted to the hospital with COVID-19 pneumonia, found to have a cerebrovascular event treated with unfractionated heparin. She also received therapeutic LMWH for anticoagulation on day 1 of presentation due to atrial fibrillation. She was diagnosed with HIT and was found to have a pulmonary embolism, aortic arch mural thrombus, and arterial thrombi in the lower extremities. As more recent studies showed HIT antibodies in COVID-19 patients who are naive for heparin-based products, COVID-19 may be an independent risk factor for the development of HIT. The role of COVID-19 in the development of HIT is uncertain. High vigilance is required to diagnose and initiate treatment for HIT early in the disease course as it can be life-threatening.

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.…”

“…The main characteristics of the 15 included studies (12 published full-texts, 1 fullpreprint report and 2 abstracts) [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] were summarized in Table 1. Across 15 studies (8,053 total patients), there were a total of 40 reported HIT patients.…”

“…Of these, 19 HIT cases and one with autoimmune HIT who had diagnosis confirmed by SRA or HIPA were included for clinical and laboratory characterization. [26][27][28][29][30][31][32][33][37][38][39] From 6 concurrent cohorts, clinical and laboratory data of 26 patients who were suspected to have HIT but had negative confirmatory tests were available for comparison. [26][27][28][29]33,37 A total of 7 studies were included for the estimation of the pooled incidence of HIT.…”

Untangling the Intricacies of Infection, Thrombosis, Vaccination, and Antiphospholipid Antibodies for COVID-19

“…The specificity of platelet factor 4 antibodies has been questioned [ 81 , 86 , 87 ]. Even more so, the concept of heparin-independent genesis of platelet factor 4 antibody during severe COVID-19 has been discussed [ 82 , 85 , 89 ]. Zhu et al provide evidence to drive the hypothesis that anti-Spike RBD antibodies may function in part to activate platelets [ 89 ].…”

“…As anticoagulants have been used for both treatment and prevention during COVID-19 especially in advanced illnesses, it is not surprising that eventually there would emerge uncommon citations of heparin-induced thrombocytopenias [76][77][78][79][80][81][82][83][84][85][86][87][88]. Most of the latter, although not all, have been associated with LAC lupus anticoagulant, anti-CL anticardiolipin, anti-ß2 anti-ß2-glycoprotein-I,…”