First-ever clinical practice guidelines aimed at standardizing the use of blood thinners during heart surgery emphasize optimal heparin dosing during bypass, identification of contraindications to heparin use and heparin alternatives, and reversal of anticoagulation.
The guidelines, published Friday afternoon, were developed by leaders in the field representing the Society of Thoracic Surgeons (STS), the Society of Cardiovascular Anesthesiologists (SCA), and the American Society of ExtraCorporeal Technology (AmSECT).
The document was published concurrently in the journals Annals of Thoracic Surgery, Anesthesia & Analgesia, and the Journal of Extra Corporeal Technology.
“It is our hope that these guidelines will help clinicians practice consistent and safe anticoagulation and that there will be more standardization in practice,” said the lead author, Linda-Shore-Lesserson, MD, director of Cardiovascular Anesthesiology at North Shore University Hospital in Manhasset, New York. “Surgeons, anesthesiologists, and perfusionists will better appreciate the science behind the practices that they conduct every day.”
The joint writing group noted that even though cardiopulmonary bypass (CPB) surgery has been widely performed for more than 50 years, succinct guidelines on the delivery of heparin and other blood thinners have not existed.
“For this and other reasons, there is enormous practice variability relating to the use and dosing of heparin, monitoring heparin anticoagulation, reversal of anticoagulation, and the use of alternative anticoagulants,” the authors wrote.
The guidelines were derived based on evaluation of close to 100 recent, highly cited studies, identified through PubMed.
The writing group stressed that there is, as yet, no ideal anticoagulation strategy for cardiac surgery with CPB in patients who cannot take heparin: “Heparin and protamine remain the gold standard for anticoagulation therapy. A small subset of patients requires heparin alternatives for the conduct of CPB. Bivalirudin seems to offer the safest heparin alternative in this setting.”
Despite bivalirudin’s short half-life of approximately 25 minutes, episodes of uncontrolled bleeding do occur, the authors noted.
“Only anecdotal experience is available to address coagulopathy in cases of bivalirudin-related hemorrhage. Consensus suggests that a multifaceted approach offers the best chance of successful hemorrhage control for these patients. Recombinant activated factor VII may be an important part of hemorrhage control, but other interventions including modified ultrafiltration, hemodialysis, and clotting factor replacement are also advocated.”
Shore-Lesserson explained that there is still a lack of definitive studies dealing with various aspects of CPB anticoagulation, especially in the area of alternative drugs to heparin. And while heparin and protamine remain the gold standard for CPB, she said, they are not perfect.
She and her co-authors called for prospective scientific trials and meta-analyses to expand the evidence base regarding anticoagulation therapy for cardiopulmonary bypass.
Specific guidelines related to heparin contraindication and alternatives include the following:
- 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 heparin-induced thrombocytopenia (HIT). (Class IIa Recommendation, Level of Evidence B)
- 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. (Class IIa Recommendation, Level of Evidence C)
- For patients who are seropositive for heparin-platelet 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 is negative, with the expectation that heparin anticoagulation therapy for CPB is likely to be safe and effective. (Class IIa Recommendation, Level of Evidence C)
- For patients with a diagnosis of HIT and who are in need of an urgent operation requiring CPB, anticoagulation with bivalirudin is a reasonable option. (Class IIa Recommendation, Level of Evidence B)
- 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, with the understanding that there are increased risks of bleeding with these interventions. (Class IIb Recommendation, Level of Evidence C)
Guidelines related to reversal of anticoagulation during CPB include:
- 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. (Class IIa Recommendation, Level of Evidence B)
- 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. (Class IIa Recommendation, Level of Evidence C)
- 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. (Class IIb Recommendation, Level of Evidence C)
- 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 re-institution of CPB with adequate anticoagulation may be lifesaving. (Class I Recommendation, Level of Evidence C)
- 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. (Class IIb Recommendation, Level of Evidence C)
The guidelines were developed by The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology.
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner