Last updated on November 11th, 2020
Based on new evidence, clinical equipoise exists and it is reasonable to consider expanded systemic anticoagulation for patients with Covid-19.
- Unfractionated Heparin may have antiviral properties based on in vitro studies discussed below
- Patients with severe COVID-19 with an elevated D-dimer or SIC score ≥ 4 may benefit from systemic heparin
- It is unclear at this time if systemic doses higher than standard prophylaxis should be used, although some are recommending it given the high rate of thrombosis with standard systemic prophylaxis (15,000 U/day) in the above studies
- Encourage weight based or targeted VTE prophylaxis regimens as standard PPX doses may be inadequate to prevent VTE
- As patients with Covid-19 may be hypercoaguable higher doses of systemic PPX may be needed
- Strongly recommend titration of systemic prophylaxis to achieve these targets in Covid-19 patients
= Supporting use article | = Neutral Article | = Contradicting use article |
Systematic Reviews/Meta-Analysis
Meta-analysis
- Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database of Systematic Reviews 2020, Issue 10. Art. No.: CD013739. Flumignan_RLG, Tinôco_JD, Pascoal_PIF, Areias_LL, Cossi_MS, Fernandes_MICD, Costa_IKF, Souza_L, Matar_CF, Tendal_B, Trevisani_VFM, Atallah_ÁN, Nakano_LCU. Search date for review – June 20, 2020
AMSTAR rating
Search sources for review - Medline PubMed, Embase, Cochrane Central, LILACS, IBECS, medRxiv, supplementary hand searches
Reviews incorporated into meta-analysis:- Tang N et al. 2020 – rated as critical (extra-high) risk of bias
- Paranjpe et al. 2020 – rated as serious (high) risk of bias
- The association between treatment with heparin and survival in patients with Covid-19. Ayerbe_L, Risco_C, Ayis_S. Journal of Thrombosis and Thrombolysis 2020;50(2):298-301.
- Clinical impact of pre-admission antithrombotic therapy in hospitalized patients with COVID-19: a multicenter observational study. Russo_V, Di Maio_M, Attena_E, Silverio_A, Scudiero_F, Celentani_D, et al. Pharmacological Research 2020; 159:104965.
Pre-peer reviewed/pre-publication studies:- Heparin induced thrombocytopenia is associated with a high risk of mortality in critical COVID-19 patients receiving heparin-involved treatment. Liu_X, Zhang_X, Xiao_Y, Gao_T, Wang_G, Wang_Z, et al. medRxiv [Preprint].
- The potential of low molecular weight heparin to mitigate cytokine storm in severe COVID-19 patients: a retrospective clinical study. Shi_C, Wang_C, Wang_H, Yang_C, Cai_F, Zeng_F, et al. medRxiv [Preprint].
- Therapeutic anticoagulation is associated with decreased mortality in mechanically ventilated COVID-19 patients. Trinh_M, Chang_DR, Govindarajulu_US, Kane_E, Fuster_V, Kohli-Seth_R, et al. medRxiv [Preprint].
Other: 22 on-going studies as of systematic review search date. Can pull from report if desired to list.
Longform Review
Systematic review covered prophylactic anticoagulants heparinoids (heparins or pentasaccharides), vitamin K antagonists, and direct anticoagulants versus active comparator, placebo, or no intervention in people hospitalized with COVID-19.
All anticoagulants
Evidence from 7 retrospective non-randomized controlled trials with 5,685 participants was insufficient (very low certainty) to answer whether anticoagulants (all types) reduced all-cause mortality. Uncertainty in the evidence was due to inconsistency in the findings and the high risk of bias in the included studies.
- (Critically high risk of bias) One study of 2,075 patients reported reduced mortality. [Ayerbe]
- (High risk of bias) One study with a subgroup of 395 people on mechanical ventilation reported reduced mortality [Paranjpe sub-group] But no difference between group for all patients.
- (Critically high risk of bias) Three studies reported no difference in mortality in 795 patients. [Liu, Tang, Russo]
- (Critically high risk of bias) One small study of 42 patients reported no mortality in either group. [Shi]
Low-certainty evidence from one high risk of bias study for (2,773 patients) increased major bleeding in the anticoagulation group:
- 3% bleeding events in anticoagulation group versus 1.9% bleeding events in the no-intervention group. (OR 1.62, 95% CI 0.96 to 2.71). Confidence reduced by imprecise estimates and serious risk of bias. [Paranjpe]
Pre-print Review
Evidence was insufficient to address hospitalization length of stay from one critical high risk of bias with 42 participants. [Shi]
Therapeutic dose versus prophylactic dose:
- Low-certainty evidence from one high risk of bias study (244 patients) for lower all-cause mortality in therapeutic group compared with the prophylactic group (adjusted hazard ratio 0.21, 95% CI 0.10 to 0.46). Confidence reduced by imprecise estimates and serious risk of bias. [Trinh]
- Low-certainty evidence from one high risk of bias study (244 patients) for no difference in major bleeding in therapeutic group compared with the prophylactic group (31.7% vs 20.5%, odds ratio 1.80, 95% CI 0.96 to 3.37). Confidence reduced by imprecise estimates and serious risk of bias. [Trinh]
- Low-certainty evidence from one high risk of bias study (244 patients) for increase length of hospitalization in therapeutic group compared with the prophylactic group (23.3 vs 15.7 days, mean difference 7.6 days, 95% CI 5.35 to 9.85). Confidence reduced by imprecise estimates and serious risk of bias. [Trinh]