ASH Guidelines on Use of Anticoagulation in Patients with COVID-19
In June 2020, ASH formed a multidisciplinary, international panel to develop guidelines on the use of anticoagulation in patients with COVID-19. The panel prioritized questions about the use of anticoagulation in critically and acutely ill patients.
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.
Access the full guidelines on the Blood Advances website:
American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19
The following recommendation has been updated and is now available for public comment. Comments can be submitted through the following survey.
In patients with COVID-19 related critical illness who do not have confirmed or suspected venous thromboembolism, should we use prophylactic-intensity vs. intermediate-intensity anticoagulation?
Draft Recommendation 1A (Updated April 7, 2021)
The American Society of Hematology (ASH) guideline panel suggests using prophylactic-intensity over intermediate-intensity anticoagulation for patients with coronavirus disease 2019 (COVID-19)–related critical illness who do not have suspected or confirmed venous thromboembolism (VTE) (low certainty of evidence).
Remarks: 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).
In patients with COVID-19 related acute illness who do not have confirmed or suspected venous thromboembolism, should we use prophylactic-intensity vs. intermediate-intensity vs. therapeutic-intensity anticoagulation?
Recommendation (Updated as of February 8, 2021)
The ASH guideline panel suggests using prophylactic-intensity over intermediate-intensity or therapeutic-intensity anticoagulation in patients with COVID-19 related acute illness who do not have suspected or confirmed VTE (conditional recommendation based on very low certainty in the evidence about effects).
Remarks: Between the time this recommendation was published online (October 27, 2020) and when it was published in Blood Advances, a press release was issued describing the results of a planned interim analysis of three randomized controlled trials, REMAP-CAP, ACTIV-4, and ATTACC (NCT 02735707, 04505774, and 04372589, respectively). In these trials, therapeutic-intensity anticoagulation was compared with prophylactic-intensity anticoagulation in moderately ill hospitalized patients with COVID-19. The ASH guideline panel plans to update this recommendation when the full results of REMAP-CAP, ACTIV-4, and ATTACC become available. Clinicians should weigh the potential benefits and harms based on the most up to date available evidence in caring for their patients.
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 and bleeding risk in hospitalized patients are available, but they have not been validated in patients with COVID-19. The panel acknowledges that higher-intensity anticoagulation may be preferred in 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 (e.g., low molecular weight heparin, unfractionated heparin, etc.) may be based on availability, resources required, familiarity, and the aim of minimizing personal protective equipment use or staff exposure to COVID-19 infected patients as well as patient-specific factors (e.g., renal function, history of heparin-induced thrombocytopenia, concerns about gastrointestinal tract absorption).
Additional Recommendation Coming Soon
In patients with COVID-19 who are being discharged from the hospital and who do not have confirmed or suspected venous thromboembolism, should we prescribe post-discharge prophylactic-intensity anticoagulation or not?
Guideline Implementation Tools and Resources
This webinar highlights the guideline recommendations along with the underlying evidence and rationale for the recommendations. A slide set is available from the webinar.
The ASH Clinical Practice Guidelines App provides easy access to every recommendation from all guidelines published by ASH, including rationale for each recommendation, benefits and harms associated with each recommended course of action, and links to the complete evidence-to-decision tables used to develop the recommendations. This app is also available via web interface.
Help your colleagues treat VTE in Patients with COVID-19 with the following teaching slide designed for easy dissemination:
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.
For more information, see Izcovich et al. A user guide to the American Society of Hematology clinical practice guidelines. Blood Adv (2020) 4 (9): 2095-2110.
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 to these recommendations.
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.
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