Antithrombotic Treatment in COVID-19

Publication Date: July 5, 2022
Last Updated: August 9, 2022

Recommendations

3.1 Antithrombotic therapy for non-hospitalized patients

In non-hospitalized patients with symptomatic COVID-19, initiation of antiplatelet therapy is not effective to reduce risk of hospitalization, arterial or venous thrombosis, or mortality. (III - No Benefit, B-R)
573
In non-hospitalized patients with symptomatic COVID-19, initiation of direct oral anticoagulant (DOAC) therapy is not effective to reduce risk of hospitalization, arterial or venous thrombosis, or mortality. (III - No Benefit, B-R)
573
In non-hospitalized patients with COVID-19 at higher risk of disease progression, initiation of oral sulodexide therapy within 3 days of symptom onset may be considered to reduce risk of hospitalization. (IIb, B-R)
573

3.2 Antithrombotic therapy for non–critically ill, hospitalized patients

In non-critically ill patients hospitalized for COVID-19, low (prophylactic) dose LMWH or UFH is recommended in preference to no LMWH or UFH to reduce risk of thromboembolism and possibly death. (I, B-NR)
573
In select non-critically ill patients hospitalized for COVID-19, therapeutic-dose LMWH or UFH is beneficial in preference to low (prophylactic) or intermediate dose LMWH or UFH to reduce risk of thromboembolism and end organ failure. (I, A)
573
In non-critically ill patients hospitalized for COVID-19, intermediate-dose LMWH or UFH is not recommended in preference to low (prophylactic) dose LMWH or UFH to reduce risk of thromboembolism and other adverse outcomes. (III - No Benefit, B-R)
573
In non-critically ill patients hospitalized for COVID-19, add-on treatment with an antiplatelet agent is potentially harmful and should not be used. (III - Harm, A)
573
In non-critically ill patients hospitalized for COVID-19, therapeutic-dose DOAC is not effective to reduce risk of thromboembolism and other adverse outcomes. (III - No Benefit, B-R)
573

3.3 Antithrombotic therapy for critically ill, hospitalized patients

In critically ill patients hospitalized for COVID-19, intermediate dose LMWH/UFH is not recommended over prophylactic dose LMWH/UFH to reduce risk of adverse events, including mortality and thromboembolism. (III - No Benefit, B-R)
573
In critically ill patients hospitalized for COVID-19, therapeutic dose LMWH/UFH is not recommended over usual-care or prophylactic dose LMWH/UFHs. (III - No Benefit, B-R)
573
In select critically ill patients hospitalized for COVID-19, add on treatment with an antiplatelet agent to prophylactic dose LMWH/UFH is not well established but might be considered to reduce mortality. (IIb, B-R)
573

3.4 Antithrombotic therapy for patients discharged from hospital

In select patients who have been hospitalized for COVID-19, post-discharge treatment with prophylactic dose rivaroxaban for approximately 30 days may be considered to reduce risk of VTE. (IIb, B-R)
573

Tables and Figures

TABLE 1. Dose levels of the anticoagulants used in the studies cited in the guideline

Having trouble viewing table?
Drug Prophylactic Intermediate Therapeutic
UFH 000 U SQ BID or TID 7500 U SQ BID or TID Intravenous, adjusted to APTT or anti-Xa
LMWH Enoxaparin 40 mg SQ QD, dalteparin 5000 IU SQ QD, tinzaparin 4500 IU SQ QD, bemiparin 3500 IU SQ QD Enoxaparin 40 mg SQ BID or 80 mg SQ QD, or 0.5 mg/kg SQ QD Enoxaparin 1 mg/kg SQ BID, dalteparin 200 IU/kg SQ QD, tinzaparin 175 IU/kg SQ QD, bemiparin 115 IU/kg SQ QD
DOAC Rivaroxaban 10 mg PO QD, apixaban 2.5 mg PO BID Not applicable Rivaroxaban 20 mg PO QD, apixaban 5 mg PO BID

FIGURE 2. Summary of recommendations


Recommendation Grading

Overview

Title

Antithrombotic Treatment in COVID-19

Authoring Organization

Publication Month/Year

July 5, 2022

Last Updated Month/Year

February 13, 2024

Supplemental Implementation Tools

Document Type

Guideline

Country of Publication

US

Document Objectives

Antithrombotic agents reduce risk of thromboembolism in severely ill patients. Patients with coronavirus disease 2019 (COVID-19) may realize additional benefits from heparins. Optimal dosing and timing of these treatments and benefits of other antithrombotic agents remain unclear. In October 2021, ISTH assembled an international panel of content experts, patient representatives, and a methodologist to develop recommendations on anticoagulants and antiplatelet agents for patients with COVID-19 in different clinical settings. We used the American College of Cardiology Foundation/American Heart Association methodology to assess level of evidence (LOE) and class of recommendation (COR). Only recommendations with LOE A or B were included. Panelists agreed on 12 recommendations: three for non-hospitalized, five for non–critically ill hospitalized, three for critically ill hospitalized, and one for post-discharge patients. Two recommendations were based on high-quality evidence, the remainder on moderate-quality evidence. Among non–critically ill patients hospitalized for COVID-19, the panel gave a strong recommendation (a) for use of prophylactic dose of low molecular weight heparin or unfractionated heparin (LMWH/UFH) (COR 1); (b) for select patients in this group, use of therapeutic dose LMWH/UFH in preference to prophylactic dose (COR 1); but (c) against the addition of an antiplatelet agent (COR 3). Weak recommendations favored (a) sulodexide in non-hospitalized patients, (b) adding an antiplatelet agent to prophylactic LMWH/UFH in select critically ill, and (c) prophylactic rivaroxaban for select patients after discharge (all COR 2b). Recommendations in this guideline are based on high-/moderate-quality evidence available through March 2022. Focused updates will incorporate future evidence supporting changes to these recommendations.

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Treatment, Management

Diseases/Conditions (MeSH)

D000991 - Antithrombins, D017934 - Coronavirus

Keywords

antithrombotic, Coronavirus, covid-19, COVID

Source Citation

Schulman S, Sholzberg M, Spyropoulos AC, Zarychanski R, Resnick HE, Bradbury CA, Broxmeyer L, Connors JM, Falanga A, Iba T, Kaatz S, Levy JH, Middeldorp S, Minichiello T, Ramacciotti E, Samama CM, Thachil J; International Society on Thrombosis and Haemostasis. ISTH guidelines for antithrombotic treatment in COVID-19. J Thromb Haemost. 2022 Jul 8:10.1111/jth.15808. doi: 10.1111/jth.15808. Epub ahead of print. PMID: 35906716; PMCID: PMC9349907.

Supplemental Methodology Resources

Data Supplement

Methodology

Number of Source Documents
60
Literature Search Start Date
January 1, 2020
Literature Search End Date
March 6, 2022