Therapeutic dosing of low-molecular-weight heparin may decrease mortality in patients with severe COVID-19 infection

Abstract

BACKGROUND: Venous thromboembolism or extensive thrombosis is relatively common in patients with severe COVID-19 infection and has been associated with increased mortality. During the current COVID-19 pandemic, several prophylactic doses and types of low-molecular-weight heparin (LMWH) are being used worldwide; however, there are no high-quality studies or recommendations for an optimal prophylactic LMWH dose. OBJECTIVES: Investigate the relationship between coagulation parameters and the LMWH dose, and mortality and ICU admission in hospitalized patients with severe COVID-19 pneumonia. DESIGN: Retrospective. SETTING: Tertiary care hospital. PATIENTS AND METHODS: Data on clinical features, coagulation parameters and anticoagulant medications of inpatients with severe COVID-19 were collected for the period between 11 March 2020 and 31 April 2020. MAIN OUTCOME MEASURES: Mortality and ICU admission for prophylactic dose LMWH (0.5 mg/kg twice daily) and therapeutic dose LMWH (1 mg/kg twice daily). SAMPLE SIZE: 154 cases. RESULTS: Ninety-eight (63.6%) patients were treated with the LMWH prophylactic dose and 56 (36.4%) patients were treated with the therapeutic dose. Forty-four (44.9%) of 98 patients using the prophylactic dose LMWH died, while 10 (17.9%) of 56 patients using the therapeutic dose LMWH died ( P =.001). Mortality was 6.4-fold higher in the prophylactic dose LMWH users than in the therapeutic dose LMWH users (OR=6.5, 95% CI: 2.4–17.6, P <.001). CONCLUSIONS: Therapeutic dosing of LMWH may decrease mortality in patients with severe COVID-19 infected pneumonia. More aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies. LIMITATIONS: Lack of information about bleeding complications. LMWH was not compared with other anticoagulant therapies. There was no comparison between our two groups on the APACHE score. Used different doses of LMWH in different clinics in our hospital. Single-center, retrospective study. CONFLICT OF INTEREST: None.

Different Anticoagulant Regimens, Mortality, and Bleeding in Hospitalized Patients with COVID-19: A Systematic Review and an Updated Meta-Analysis

“…Four studies were from China, 20,21,42,47 14 from Europe, 22,23,28,29,31,32,34,35,40,41,43,44,46,48 and 11 from United States (►Table 1). [24][25][26][27]30,33,[36][37][38][39]45 All were retrospective observational studies.…”

“…29 Eighteen studies reported data exclusively for heparin (UFH or LMWH) treatment. [20][21][22][23]28,[30][31][32]34,35,[40][41][42][43][44][46][47][48] Six studies investigated the role of any anticoagulant treatment, including LMWH or UFH, direct thrombin inhibitors, and/or direct oral anticoagulants. 24,33,[36][37][38]45 Only one study investigated three types of anticoagulant drugs separately (i.e., apixaban, enoxaparin, UFH).…”

“…20,21,23,[25][26][27]29,[31][32][33][34][35][36][37]39,41,42,45,47,48 Additionally, 13 studies compared two groups of patients at different dosages of anticoagulant (therapeutic vs. prophylactic) (►Table 2). 22,24,28,30,33,34,37,38,40,43,44,46,48 The studies were mostly considered of good quality (23/29) (►Supplementary Table S1). 50 Wide heterogeneity was found regarding the outcomes investigated (domain 3), the type of anticoagulant used, and the definition of the dosage (domains 1 and 2).…”

“…Thirteen studies compared two different dosages of anticoagulant treatment. 22,24,28,30,33,34,37,38,40,43, 44,46,48 The defi-nitions of therapeutic or prophylactic dose were different among studies (►Table 2). In the majority of the works reporting heparins' dosages (66%), the prophylactic dosage included UFH <5,000 IU; enoxaparin 20 to 40 mg/daily or 1 mg/kg/daily; therapeutic dosage included 5,000 > UFH < 15,000 IU; enoxaparin > 40 mg/daily or 1 mg/kg twice or three times daily (►Table 2).…”

“…In the majority of the works reporting heparins' dosages (66%), the prophylactic dosage included UFH <5,000 IU; enoxaparin 20 to 40 mg/daily or 1 mg/kg/daily; therapeutic dosage included 5,000 > UFH < 15,000 IU; enoxaparin > 40 mg/daily or 1 mg/kg twice or three times daily (►Table 2). 24,30,34,37,38,44,46,48 The study by Pesavento et al reported that the rate for overall mortality was 12.2 (95% CI: 8.1-17.8) per 100 persons/month in patients who received LMWH prophylactic doses and 20.1 (95% CI: 11.0-33.8) per 100 persons/month in those treated with higher doses, defined as subtherapeutic. 28 Di Castelnuovo et al showed that both prophylactic and therapeutic regimens were effective in reducing mortality, the prophylactic doses to a higher extent (HR: 1.54, 95% CI: 1.06-2.25).…”