Heparin-Induced Thrombocytopenia Is a High Risk of Mortality in Critical COVID-19 Patients Receiving Heparin-Involved Treatment

Abstract

Background: The coronavirus infectious disease 2019 (COVID-19) has developed into a global pandemic. It is essential to investigate the clinical characteristics of COVID-19 and uncover the potential risks of mortality to reduce the overall mortality rate of COVID-19. Methods: 61 critical COVID-19 patients admitted into intensive care unit (ICU) and 93 severe non-ICU patients in Huoshenshan Hospital (Wuhan, China) were included in this study. The medical records of demographic, platelet counts, heparin-involved treatments, heparin-induced thrombocytopenia (HIT) related laboratory tests, and the fatal outcomes of these patients were analyzed and compared between survivors and non-survivors. Findings: Among 61 critical ICU patients, including 15 survivors and 46 non-survivors, 41% of them (25/61) had severe thrombocytopenia with platelet count less than 50´109/L, of whom 76% (19/25) had a >50% platelet fall compared to baseline and 96% (24/25) had a fatal outcomes. Among 46 non-survivors, 52·2% (24/46) had severe thrombocytopenia, compared to 6·7% (1/15) in survivor. Moreover, continuous renal replacement therapy (CRRT) could induce significant decrease of platelet count in 81·3% of critical CRRT patients (13/16), resulting in a fatal outcome. Next, high level of anti-Heparin-PF4 antibodies, a marker of heparin-induced thrombocytopenia (HIT), was observed in most of ICU patients. Surprisingly, HIT occurred not only in patients with heparin exposure such as CRRT but also in heparin-naive patients, suggesting that a spontaneous HIT might occur in COVID-19. Interpretation: Anti-heparin-PF4 antibodies are induced in critical COVID-19 patients, resulting in a progressive platelet decrease. Exposure to high dose of heparin may trigger further severe thrombocytopenia with a fatal outcome. An alternative anticoagulant other than heparin should be used in the therapy of COVID-19 patients in critical condition. Funding Statement: This investigation was supported by Grant 2016CB02400 and 2017YFC1201103 from National Major Research and Development Program of China. Declaration of Interests: Authors declare no potential conflicts of interests. Ethics Approval Statement: This study was approved by the Ethics Committee of Huoshenshan Hospital (Wuhan, China).