Guidelines for Anticoagulation in Hospitalized COVID-19 Patients ≥ 18 Years of Age
BACKGROUND
• Severe COVID-19 disease is associated with features of disseminated intravascular coagulation (DIC) and hypercoagulable states which can manifest as venous thromboembolism (VTE) and/or microthrombosis.1,2

• Centers for Disease Control and Prevention (CDC) estimates approximately 90% of hospitalized COVID-19 patients have underlying disease states such as obesity, hypertension, chronic lung disease, diabetes, and heart disease, which may increase the risk of thrombosis.3
• Critically ill patients with COVID-19 have been reported to have a VTE incidence rate around 30% which is significantly higher than non-COVID-19 critically ill populations4,5

• A study of 449 COVID-19 patients found that deep vein thrombosis (DVT) prophylaxis decreased 28-day mortality by 20% in patients with a D-dimer ≥ 3,000 ng/mL or a sepsis-induced coagulopathy (SIC) score ≥ 4 without increasing rates of major bleeding.6

• Elevated D-dimer is associated with worse outcomes;7-9 Recent studies have found d-dimer above certain thresholds to have a high positive predictive value for VTE events and suggest these thresholds may be useful in determining when ultrasound screening and even empiric full dose anticoagulation is indicated.4

• Randomized controlled trials evaluating empiric full dose anticoagulation in patients with COVID-19 without a diagnosed indication (e.g. venous or arterial thrombosis, stroke prevention in atrial fibrillation, heart valve replacements) or clinical signs of clotting are currently underway. In the meantime, however many institutions are implementing empiric full dose anticoagulation based on the risk of VTE and overall low incidence of bleeding (3-5%).10,11

• Hospitalized patients with a diagnosis necessitating therapeutic anticoagulation should be treated with treatment dose unfractionated or low molecular weight heparin instead of direct oral anticoagulants (DOACs) and warfarin which are less desirable due to illness-related hepatic dysfunction, reduced appetite and poor oral intake which may affect absorption or affect response to warfarin, and the possibility of rapid deterioration.12

• Incidence of VTE and major bleeding in COVID19 patients post-discharge are unknown. The decision to prescribe extended thromboprophylaxis should be individualized and based on the patients VTE and bleed risk.14

• The algorithm below is intended to provide guidance for anticoagulation prophylaxis and treatment in COVID-19 patients and should not supersede clinical judgement. It may also be applied to “Persons Under Investigation” (PUIs) at the physician’s discretion.



REFERENCES

1. Yuriditsky E, Horowitz JM, Merchan C, et al. Thromboelastography profiles of critically ill patients with coronavirus disease 2019. Crit Care Med. 2020; [published online ahead of print]. https://doi.org/10.1097/ccm.0000000000004471
2. Lin L, Lu L, Cao W, et al. Hypothesis for potential pathogensis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes & Infect.2020;9(1):727-732.

3. Garg S, Kim L, Whitaker M, et al. Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 — COVID-NET, 14 States, March 1–30, 2020. MMWR Morb Mortal Wkly Rep 2020;69:458–464. DOI: http://dx.doi.org/10.15585/mmwr.mm6915e3
4. Trigonis RA, Holt DB, Yuan RY, et al. Incidence of thromboembolism in critically ill coronavirus disease 2019 patients receiving prophylactic anticoagulation. Crit Care Med. 2020; [published online ahead of print]. doi: 10.1097/CCM.0000000000004472

5. Klok FA, Kruip MJ, Van der Meer NJ, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID19. Throm Res.2020 (191);145-147.
6. Tang N, Bai H, Chen X, et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020(18);1094–1099.
7. Guan W, Ni Z, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720.
8. Tang N, Li D, Wang X, et al. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18:844- 847.
9. Yin S, Huang M, Li D, et al. Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2. J Throm Thrombolysis.2020; [published online ahead of print] doi.org/10.1007/s11239-020-02105-8
10. Paranjpe I, Fuster V, Lala A, et al. Association of treatment dose anticoagulation with in-hospital survival among hospitalized patients with COVID-19. JACC. 2020;76(1):122-29.
11. Al-Samkar H, Leaf RK, Dzik W, et al. COVID and coagulation: bleeding and thrombotic manifestations of SARS-CoV2 infection. Blood. 2020;[published ahead of print]. https://doi.org/10.1182/blood.2020006520
12. Barnes GD, Burnett A, Allen A, et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: Interim clinical guidance from the Anticoagulation Forum. J Thromb Thrombolysis. 2020;50(1):72-81.
13. Moores LK, Tritschler T, Brosnahan S, Prevention, diagnosis and treatment of venous thromboembolism in patients with COVID-19: CHEST Guideline and Expert Panel Report. Chest.2020;[published online ahead of print] https://doi.org/10.1016/j.chest.2020.05.559

Created by Christina Gutierrez, PharmD, Crystal Franco-Martinez, PharmD, Jose Gonzalez, PharmD, & Dana Foster, PharmD: 4/14/2020 Revised by Crystal Franco-Martinez, PharmD, Christina Gutierrez, PharmD, and Jose Gonzalez, PharmD: 7/13/2020 Reviewed by Rebecca Attridge PharmD, Diego J Maselli MD, Omar Enriquez MD, Vincent Gould AGACNP-BC, Maria Velez MD & Adriel Malave MD: 7/15/2020 Approved by Anticoagulation Safety Committee (expedited approval): 4/16/2020; 7/27/2020 Approved by Pharmacy & Therapeutics Committee (expedited approval): 4/17/2020; 8/6/2020