Key result
Continuous renal replacement therapy, which involves heparin exposure, induced severe thrombocytopenia in 81.3% of critical COVID-19 patients compared to 26.7% in non-CRRT patients.
Why the study?
Investigating clinical characteristics and uncovering potential risk factors for severe disease was needed to reduce the overall mortality rate of COVID-19.
Does heparin exposure increase the risk of severe thrombocytopenia and mortality in critical COVID-19 patients?
Observational (n=154)
No
Does heparin exposure increase the risk of severe thrombocytopenia and mortality in critical COVID-19 patients?
Absolute Event Rate: 81.3% vs 26.7%
p-value: p=0.0004363
Heparin exposure, particularly through CRRT, is associated with severe thrombocytopenia and high mortality in critical COVID-19 patients, suggesting the occurrence of spontaneous or heparin-induced thrombocytopenia.
Heparin-exposed CRRT was associated with severe thrombocytopenia; leaves open HIT mechanisms and should not yet change practice.
Summary Background 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 potential risk factors for severe disease to reduce the overall mortality rate of COVID-19. Methods Sixty-one critical COVID-19 patients admitted to the intensive care unit (ICU) and 93 severe non-ICU patients at Huoshenshan Hospital (Wuhan, China) were included in this study. Medical records, including demographic, platelet counts, heparin-involved treatments, heparin-induced thrombocytopenia-(HIT) related laboratory tests, and fatal outcomes of COVID-19 patients were analyzed and compared between survivors and nonsurvivors. Findings Sixty-one critical COVID-19 patients treated in ICU included 15 survivors and 46 nonsurvivors. Forty-one percent of them (25/61) had severe thrombocytopenia, with a platelet count (PLT) less than 50×10 9 /L, of whom 76% (19/25) had a platelet decrease of >50% compared to baseline; 96% of these patients (24/25) had a fatal outcome. Among the 46 nonsurvivors, 52·2% (24/46) had severe thrombocytopenia, compared to 6·7% (1/15) among survivors. Moreover, continuous renal replacement therapy (CRRT) could induce a significant decrease in PLT in 81·3% of critical CRRT patients (13/16), resulting in a fatal outcome. In addition, a high level of anti-heparin-PF4 antibodies, a marker of HIT, was observed in most ICU patients. Surprisingly, HIT occurred not only in patients with heparin exposure, such as CRRT, but also in heparin-naïve patients, suggesting that spontaneous HIT may occur in COVID-19. Interpretation Anti-heparin-PF4 antibodies are induced in critical COVID-19 patients, resulting in a progressive platelet decrease. Exposure to a high dose of heparin may trigger further severe thrombocytopenia with a fatal outcome. An alternative anticoagulant other than heparin should be used to treat COVID-19 patients in critical condition. Funding This investigation was supported by grants 2016CB02400 and 2017YFC1201103 from the National Major Research and Development Program of China.
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Liu et al. (2020) conducted an observational in COVID-19 (n=154). Continuous renal replacement therapy (CRRT) / Heparin exposure vs. Non-CRRT / No heparin exposure was evaluated on Severe thrombocytopenia (PLT ≤ 50 × 10^9/L) (p=0.0004363). Continuous renal replacement therapy, which involves heparin exposure, induced severe thrombocytopenia in 81.3% of critical COVID-19 patients compared to 26.7% in non-CRRT patients.
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