ASH Guidelines on Use of Anticoagulation in Patients with COVID-19

The ASH guideline panel plans to continue to update this recommendation when the full results of other trials become available. Clinicians should weigh the potential benefits and harms based on the most up-to-date available evidence in caring for their patients.

A now expired recommendation published on October 27, 2020 compared therapeutic-intensity or intermediate-intensity with prophylactic-intensity anticoagulation in patients with COVID-19-related critical illness. With the emergence of new evidence, this recommendation has now been split into two recommendations: a recommendation comparing intermediate-intensity vs. prophylactic-intensity anticoagulation (Recommendation 1A) and a separate recommendation comparing therapeutic-intensity vs. prophylactic-intensity anticoagulation (Recommendation 1B).

Patients with COVID-19–related critical illness are defined as those suffering from an immediately life-threatening condition who would typically be admitted to an intensive care unit (ICU). Examples include patients requiring hemodynamic support, ventilatory support, and renal-replacement therapy.

An individualized assessment of the patient’s risk of thrombosis and bleeding is important when deciding on anticoagulation intensity. Risk-assessment models to estimate thrombotic and bleeding risk in hospitalized patients are available, but they have not been validated for patients with COVID-19. The panel acknowledges that higher-intensity anticoagulation may be preferred for patients judged to be at high thrombotic risk and low bleeding risk.

At present, there is no direct high-certainty evidence comparing different types of anticoagulants. The selection of a specific agent (eg, low-molecular-weight heparin, unfractionated heparin, etc) may be based on availability, resources required, familiarity, and the aim of minimizing personal protective equipment (PPE) use or staff exposure to COVID-19–infected patients as well as patient-specific factors (eg, renal function, history of heparin-induced thrombocytopenia, concerns about gastrointestinal tract absorption).
This recommendation does not apply to patients who require anticoagulation to prevent thrombosis of extracorporeal circuits such as those on extracorporeal membrane oxygenation (ECMO) or continuous renal-replacement therapy (CRRT).

Patients with COVID-19–related critical illness are defined as those suffering from an immediately life-threatening condition who would typically be admitted to an intensive care unit (ICU). Examples include patients requiring hemodynamic support, ventilatory support, and renal replacement therapy.

A separate recommendation (1A) addresses the comparison of intermediate-intensity and prophylactic-intensity anticoagulation in critically ill COVID-19 patients.

An individualized assessment of the patient’s risk of thrombosis and bleeding is important when deciding on anticoagulation intensity. Risk-assessment models to estimate thrombotic risk have been validated in hospitalized COVID-19 patients (critically or non-critically ill), with modest prognostic performance. No risk assessment models for bleeding have been validated in COVID-19 patients. The panel acknowledges that higher-intensity anticoagulation may be preferred for patients judged to be at low bleeding risk and high thrombotic risk.

At present, there is no direct high-certainty evidence comparing different types of anticoagulants in patients with COVID-19. Unfractionated or low molecular weight heparin were used in most of the identified studies.

This recommendation does not apply to patients who require anticoagulation to prevent thrombosis of extracorporeal circuits such as those on extracorporeal membrane oxygenation or continuous renal replacement therapy.

Patients with COVID-19–related acute illness are defined as those with clinical features that would typically result in admission to a medicine inpatient ward without requirement for advanced clinical support. Examples include patients with dyspnea or mild to moderate hypoxia.

An individualized assessment of the patient’s risk of thrombosis and bleeding is important when deciding on anticoagulation intensity. Risk-assessment models to estimate thrombotic risk in hospitalized patients have been validated in COVID-19 patients, with modest prognostic performance. No risk assessment models for bleeding have been validated in COVID-19 patients. The panel acknowledges that lower-intensity anticoagulation may be preferred for patients judged to be at high bleeding risk and low thrombotic risk.

At present, there is no direct high-certainty evidence comparing different types of anticoagulants in patients with COVID-19. Unfractionated or low molecular weight heparin may be preferred because of a preponderance of evidence with these agents.

The ASH guideline panel did not continue to review updated evidence regarding intermediate-intensity vs. therapeutic-intensity anticoagulation for acutely ill patients after the publication dated February 8, 2021.

Patients with COVID-19–related acute illness are defined as those with clinical features that would typically result in admission to a medicine inpatient ward without requirement for advanced clinical support. Examples include patients with dyspnea or mild to moderate hypoxia.

An individualized assessment of the patient’s risk of thrombosis and bleeding is important when deciding on anticoagulation intensity. Risk-assessment models to estimate thrombotic risk in hospitalized patients have been validated in COVID-19 patients, with modest prognostic performance. No risk assessment models for bleeding have been validated in COVID-19 patients.

An individualized assessment of the patient’s risk of thrombosis and bleeding and shared decision-making is important when deciding whether to use post discharge thromboprophylaxis. The panel acknowledged that post-discharge thromboprophylaxis may be reasonable in patients judged to be at high thrombotic risk and low bleeding risk.

ASH guidelines are primarily intended to help clinicians make decisions about diagnostic and treatment alternatives. Other purposes are to inform policy, education and advocacy, and to state future research needs. They may also be used by patients. These guidelines are not intended to serve or be construed as a standard of care. Clinicians must make decisions on the basis of the clinical presentation of each individual patient, ideally through a shared process that considers the patient’s values and preferences with respect to the anticipated outcomes of the chosen option. Decisions may be constrained by the realities of a specific clinical setting and local resources, including but not limited to institutional policies, time limitations, or availability of treatments. These guidelines may not include all appropriate methods of care for the clinical scenarios described. As science advances and new evidence becomes available, recommendations may become outdated. Following these guidelines cannot guarantee successful outcomes. ASH does not warrant or guarantee any products described in these guidelines.

Statements about the underlying values and preferences as well as qualifying remarks accompanying each recommendation are its integral parts and serve to facilitate more accurate interpretation. They should never be omitted when quoting or translating recommendations from these guidelines. Implementation of the guidelines will be facilitated by the evidence-to-decision frameworks and summary of findings tables linked above and by other implementation tools linked below.

In June 2020, ASH formed a multidisciplinary, international panel to develop guidelines on the use of anticoagulation in patients with COVID-19.

The McMaster University GRADE Centre supported the guideline development process. In collaboration with experts on the guideline panel, the team conducted urgent systematic reviews of available evidence on the baseline risk of thrombosis in patients with COVID-19 and on the use of prophylactic versus higher intensity anticoagulation in patients who are acutely or critically ill.

These guidelines are informed by living systematic reviews of available evidence, i.e., monthly literature searches and, as needed, updates to estimates for the baseline risk of thrombosis or the effects of anticoagulation. If and when estimates change, the guideline panel will reconvene to consider changes.

Cuker A, Tseng EK, Nieuwlaat R, et al. American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19. Blood Advances. 2021;5(3):872-888.  For additional information regarding update history, contact [email protected].