University

V Health System
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) with coagulopathy.
• The large inflammatory response is implicated in induction of this pro-thrombotic state.
• 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.1
• The Centers for Disease Control and Prevention (CDC) estimates that approximately 90% of hospitalized COVID-19 patients have one or more
underlying disease states such as obesity, hypertension, chronic lung disease, diabetes, and heart disease, some of which are associated
with increased risk of thrombosis and severe disease.2
• A study of 184 ICU patients with COVID-19 pneumonia demonstrating a 31% incidence of thrombotic complications reinforces
recommendations to continue to provide DVT prophylaxis and consider higher-dose prophylaxis in this high-risk population.3
• Elevated D-dimer is associated with worse outcomes;4-6 however, fluctuations with severity of illness highlight the importance for treatment
decisions to be based on overall clinical features vs. a single factor or lab value.
• Currently, there is no evidence to support full dose anticoagulation as a preventative measure in COVID-19 patients without a diagnosed
indication (e.g. venous or arterial thrombosis, stroke prevention in atrial fibrillation, heart valve replacements) or clinical signs of clotting.
• Patients with a diagnosis necessitating therapeutic anticoagulation should be treated with treatment dose unfractionated or low molecular
weight heparin while hospitalized, vs. direct oral anticoagulants (DOACs) which are less desirable due to illness-related hepatic dysfunction,
reduced appetite and poor oral intake which may affect absorption, and the possibility of rapid deterioration.
• 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.

Created by: Christina Gutierrez, PharmD, Crystal Franco-Martinez, PharmD, Jose Gonzales, PharmD, & Dana Foster, PharmD: 4/14/2020
Reviewed by: Maria Velez, MD & Adriel Malave, MD: 4/15/2020
Approved by Anticoagulation Safety Committee (expedited approval): 4/16/2020
Pharmacy and Therapeutics Committee (expedited approval): 4/17/2020
 j COVID-19 (+) patient ≥ 18 years of age
with no contraindications to anticoagulation
DVT Prophylaxis
i
Critically Ill DVT Prophylaxis
Non-Critically Ill
Indication for Anticoagulation
Treatment BMI < 40: Enoxaparin 40 mg SC once daily***
D-dimer > 2,000 – 3,000 ng/mL* (Thrombosis, atrial fibrillation, BMI ≥ 40: Enoxaparin 40 mg SC BID
OR heart valve replacement) BMI ≥ 50: Enoxaparin 60 mg SC BID
SIC score ≥ 4 (See APPENDIX)
Use Enoxaparin or Heparin with/without CrCl < 30 mL/min:
1 Warfarin per standard Enoxaparin 30 mg SC once daily**
I dosing protocols Heparin 5,000 units SC every 8 hrs
YES NO ≥ 100 kg: Heparin 7,500 units SC every 8 hrs
t f
Consider “High Dose Prophylaxis” if
High Dose Prophylaxis Enoxaparin 30 mg SC BID D-dimer ≥ 2,000-3,000 ng/mL* or SIC score ≥ 4
BMI ≥ 40: Enoxaparin 40 mg SC BID (See APPENDIX)
Enoxaparin 0.5 mg/kg SC BID (TBW)** BMI ≥ 50: Enoxaparin 60 mg SC BID
Avoid DOACs for prophylaxis during hospitalization
CrCl < 30 mL/min: CrCl < 30 mL/min:
Enoxaparin 0.5 mg/kg SC once daily** Enoxaparin 30 mg SC once daily**
< 50 kg: Heparin 5,000 units SC every 8 hrs Heparin 5,000 units SC every 8 hrs
≥ 50 kg: Heparin 7,500 units SC every 8 hrs ≥ 100 kg: Heparin 7,500 units SC every 8 hrs
0 t t -~
Extended Prophylaxis Post-Discharge
(Consider prescribing DVT prophylaxis upon discharge for 2-4 weeks as patients remain at risk for thrombosis)
Rivaroxaban 10 mg PO once daily (avoid in hepatic dysfunction) OR Enoxaparin 40 mg SC once daily
CrCl < 30 mL/min:
Enoxaparin 30 mg SC once daily
Heparin 5,000 units SC every 8 hrs
*Clinicians should check D-dimer at baseline, then at least weekly and with changes in severity of illness.
**May consider checking LMW heparin assay 4 hrs after the 2nd dose at provider’s discretion to ensure target level (0.2-0.4) achieved or assess for potential
drug accumulation in severe renal disease.
***Patients presenting with trauma should continue to receive Enoxaparin 30 mg SC BID per standard practice.
DOACs = Direct oral anticoagulants (apixaban, rivaroxaban, dabigatran, edoxaban, betrixaban)
Created by: Christina Gutierrez, PharmD, Crystal Franco-Martinez, PharmD, Jose Gonzales, PharmD, & Dana Foster, PharmD: 4/14/2020
Reviewed by: Maria Velez, MD & Adriel Malave, MD: 4/15/2020
Approved by Anticoagulation Safety Committee (expedited approval): 4/16/2020
Pharmacy and Therapeutics Committee (expedited approval): 4/17/2020
REFERENCES

1. Tang N, Bai H, Chen X, et al. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients
with coagulopathy.2020;Doi:10.1111/JTH.14817
2. 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
3. Klok FA, Kruip MJ, Van der Meer NJ, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID19. Thrombosis
Research [ahead of print]
4. Guan W, Ni Z, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. NEJM March 2020
5. 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.
6. Yin S, Huang M, Li D, et al. Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2.
Journal of Thrombosis and Thrombolysis.2020; doi.org/10.1007/s11239-020-02105-8
7. Iba T, DiNisio M, Levy J, et al. New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective
analysis of a nationwide survey. BMJ Open.2017;7(9)e017046).
8. 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. Emerging Microbes & Infections.2020; DOI: 10.1080/22221751.2020.1746199.
9. Li T, Lu H, Zhang W. Clinical observation and management of COVID-19 patients. Emerging Microbes & Infection.2020;
doi/full/10.1080/22221751.2020.1741327

APPENDIX

ISTH SIC score7

Score Range
1 100 - 150
Platelet count (X 109/L)
2 < 100
1 1.2 - 1.4
PT-INR
2 > 1.4
1 1
Total SOFA score*
2 ≥2
Total score for SIC ≥4
*Total SOFA score is the sum of the four items (respiratory SOFA, cardiovascular SOFA, hepatic SOFA, and renal SOFA)

Created by: Christina Gutierrez, PharmD, Crystal Franco-Martinez, PharmD, Jose Gonzales, PharmD, & Dana Foster, PharmD: 4/14/2020
Reviewed by: Maria Velez, MD & Adriel Malave, MD: 4/15/2020
Approved by Anticoagulation Safety Committee (expedited approval): 4/16/2020
Pharmacy and Therapeutics Committee (expedited approval): 4/17/2020