Anticoagulation During Cardiopulmonary Bypass

Publication Date: March 1, 2018
Last Updated: March 14, 2022

Recommendations

Heparin Dosing for Initiation and Maintenance of CPB

A functional whole blood test of anticoagulation, in the form of a clotting time, should be measured and should demonstrate adequate anticoagulation before initiating and at regular intervals during CPB. (Level C, Class I (benefit > > >risk))
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Bolus administration of unfractionated heparin based on weight is reasonable for achieving adequate anticoagulation, but individual response to heparin is heterogeneous and requires a therapeutic functional test of clot inhibition before initiation of CPB, independent of the bolus dose used. (Level C, Class IIa (benefit > > risk))
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It is reasonable to use activated clotting time (ACT) tests that produce “maximally activated” clotting times as these tests mitigate ACT variability, are less susceptible to hypothermia, and correlate more closely with factor Xa activity compared with tests that use a single activator. (Level B, Class IIa (benefit > > risk))
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It is reasonable to maintain activated clotting time above 480 seconds during CPB. However, this minimum threshold value is an approximation and may vary based on the bias of the instrument being used. For instruments using maximal activation of whole blood or microcuvette technology, values above 400 seconds are frequently considered therapeutic. (Level C, Class IIa (benefit > > risk))
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Use of a heparin dose-response formula may identify reduced sensitivity to heparin, but has not been shown to be more useful than weight-based heparin dosing in determining the heparin dose required to achieve an adequate ACT for initiation of CPB. (Level B, Class IIb (benefit > >risk))
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Use of heparin concentration monitoring in addition to ACT might be considered for the maintenance of CPB, as this strategy has been associated with a significant reduction in thrombin generation, fibrinolysis, and neutrophil activation. However, its effects on postoperative bleeding and blood transfusion are inconsistent. (Level B, Class IIb (benefit > >risk))
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During CPB, routine administration of unfractionated heparin at fixed intervals, with ACT monitoring, might be considered and offers a safe alternative to heparin concentration monitoring. (Level C, Class IIb (benefit > >risk))
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Heparin Contraindications and Heparin Alternatives

Clinical scoring estimates that use a fall in platelet count greater than 50% or a thrombotic event between 5 and 14 days after a heparin exposure can be used to determine whether a heparin–platelet antibody test should be performed to diagnose heparininduced thrombocytopenia (HIT). (Level B, Class IIa (benefit > > risk))
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Serum tests that include functional testing with serotonin release assay (SRA) or heparin-induced platelet activation (HIPA) can be beneficial in identifying patients with HIT who have a history of thrombocytopenia, and elevated clinical HIT risk scores, when platelet factor 4 (PF4)–heparin antibody testing is inconclusive (weakly positive) for HIT. (Level C, Class IIa (benefit > > risk))
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For patients who are seropositive for heparinplatelet antibodies or have a recent history of HIT, it is reasonable to delay elective cardiac operations requiring CPB until a patient’s functional test or antigenic (antibody) assay are negative, with the expectation that heparin anticoagulation therapy for CPB is likely to be safe and effective. (Level C, Class IIa (benefit > > risk))
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For patients with a diagnosis of HIT and in need of an urgent operation requiring CPB, anticoagulation with bivalirudin is a reasonable option. (Level B, Class IIa (benefit > > risk))
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In patients with significant renal dysfunction who are seropositive for HIT and require urgent operation requiring CPB, use of plasmapheresis, argatroban, or heparin with antiplatelet agents (such as tirofiban, ilioprost) may be considered, understanding that there are increased risks of bleeding with these interventions. (Level C, Class IIb (benefit > >risk))
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Reversal of Anticoagulation During Cardiac Operations

Protamine dosing for heparin reversal: It can be beneficial to calculate the protamine reversal dose based on a titration to existing heparin in the blood as this technique has been associated with reduced bleeding and blood transfusion. (Level B, Class IIa (benefit > > risk))
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Protamine overdose: It is reasonable to limit the ratio of protamine/heparin to less than 2.6 mg protamine per 100 units heparin because total doses above this ratio inhibit platelet function, prolong ACT, and increase the risk of bleeding.

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Heparin rebound: Because of the risk of heparin rebound in patients requiring high doses of heparin and with prolonged CPB times, low-dose protamine infusion (25 mg/h) for as long as 6 hours after the end of CPB may be considered as part of a multimodality blood conservation program. (Level C, Class IIb (benefit > >risk))
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Complications associated with protamine reversal of heparin after CPB: For patients at high risk for anaphylactic response to protamine who have pulmonary hypertension and circulatory collapse shortly after protamine administration, discontinuation of protamine and implementation of resuscitative measures including reinstitution of CPB with adequate anticoagulation may be lifesaving. (Level C, Class I (benefit > > >risk))
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Anticoagulation reversal when using heparin alternatives and direct thrombin inhibitors: For patients requiring anticoagulation with bivalirudin who have excessive bleeding after CPB, a combination of modified ultrafiltration, hemodialysis, and the administration of recombinant factor VIIa with blood product replacement may be considered to improve hemostasis in these extreme situations. (Level C, Class IIb (benefit > >risk))
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Recommendation Grading

Overview

Title

Anticoagulation During Cardiopulmonary Bypass

Authoring Organizations

American Society of Extracorporeal Technology

Society of Cardiovascular Anesthesiologists

Society of Thoracic Surgeons

Publication Month/Year

March 1, 2018

Last Updated Month/Year

June 9, 2022

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

To fill the evidence gap and to establish best practices in anticoagulation for CPB using the available evidence.

Inclusion Criteria

Female, Male, Adolescent, Adult, Child, Older adult

Health Care Settings

Hospital, Operating and recovery room

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Management

Diseases/Conditions (MeSH)

D003327 - Coronary Disease, D001026 - Coronary Artery Bypass

Keywords

anticoagulation, cardiopulmonary bypass, Anticoagulation

Source Citation

Shore-Lesserson L, Baker RA, Ferraris V, et al. STS/SCA/AmSECT Clinical Practice Guidelines: Anticoagulation during Cardiopulmonary Bypass. J Extra Corpor Technol. 2018;50(1):5‐18.

Supplemental Methodology Resources

Data Supplement

Methodology

Number of Source Documents
118
Literature Search Start Date
January 1, 2000
Literature Search End Date
December 31, 2015
Description of External Review Process
The clinical guideline was rigorously peer reviewed at each participating society per their society's policy and procedures.
Specialties Involved
Anesthesiology, Cardiology, Thoracic Surgery
Description of Systematic Review
To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015. The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications.
List of Questions
Recommendations were written in the three following areas: (1) heparin dosing and monitoring for initiation and maintenance of CPB; (2) heparin contraindications and heparin alternatives; and (3) reversal of anticoagulation during cardiac operations.
Description of Study Criteria
The literature search must be systematic and documented including search terms and databases searched. Before the results of the literature search are reviewed, the Task Force members must clearly define the inclusion/exclusion criteria for selecting relevant publications, including the populations and interventions to be studied, and the outcomes being measured. A brief description of the search is included in the methods section of the published guideline. The detailed search strategy is posted on the STS Auxiliary Annals page on the STS website as supporting material for the guideline. If the systematic search does not identify enough published evidence to support guideline development, the Task Force members may choose to write a Systematic Review instead.
Description of Search Strategy
To identify relevant evidence, a systematic review was outlined and literature searches were conducted in PubMed using standardized medical subject heading (MeSH) terms from the National Library of Medicine list of search terms. Search dates were inclusive of January 2000 to December 2015.
Description of Study Selection
The search yielded 833 abstracts, which were reviewed by two independent reviewers. Once accepted into the full manuscript review stage, two members of the writing group evaluated each of 286 full papers for inclusion eligibility into the guideline document. Ninety-six manuscripts were included in the final review. In addition, 17 manuscripts published before 2000 were included to provide method, context, or additional supporting evidence for the recommendations as these papers were considered sentinel publications.
Description of Evidence Analysis Methods
The review and critical appraisal of the literature must be documented and transparent. A flow chart showing the number of journal articles identified in the initial search and the number of articles passing through each stage of validation is shown on the Auxiliary Annals page on the STS website. Evidence tables that summarize the studies on which the guidelines are based also are available as supplemental materials on this website.
Description of Evidence Grading
The quality of information for a given recommendation allowed assessment of the level of evidence as recommended by the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
Description of Recommendation Grading
The quality of information for a given recommendation allowed assessment of the level of evidence as recommended by the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
Description of Funding Source
STS provides funding for STS Guideline Development.
Company/Author Disclosures
The Task Force Chair and a majority of the Task Force members must be free of Conflicts of Interest (COI). Prospective Task Force members must disclose potential COI during the selection process. Task Force members agree not to enter into new, potentially conflicting relationships during the writing of the guideline and for one year after publication. Task Force members are asked to update their COI disclosures every year, or when there is a change of status. Task Force members with a COI are not permitted to vote on recommendations related to that particular topic but may vote on recommendations not related to the topic in which there is a COI. A table containing the Task Force members’ names and their relevant COI is included in the supporting materials on the Auxiliary Annals page on the STS website.
Percentage of Authors Reporting COI
100