The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology

Clinical Practice Guidelines—Anticoagulation During Cardiopulmonary Bypass

Linda Shore-Lesserson, MD; Robert A. Baker, PhD, CCP; Victor A. Ferraris, MD, PhD; Philip E. Greilich, MD; David Fitzgerald, MPH, CCP; Philip Roman, MD, MPH; John W. Hammon, MD


Anesth Analg. 2018;126(2):413-424. 

In This Article

Alternate Agents Used to Reverse Heparin Anticoagulation

Reversal of heparin with protamine affects platelet aggregation and whole blood clotting.[94] The overwhelming convenience of protamine reversal of heparin makes it the drug of choice for heparin neutralization despite potential adverse effects on platelet and clotting function. There are patients who are unable to receive protamine for various reasons. For this reason, PF4 has been investigated as a heparin reversal agent in ex vivo animal studies and occasional case reports.[114–116] The PF4 is released by activated platelets and has strong attraction for heparin. Studies show that recombinant PF4 provides adequate heparin neutralization. However, preformed antibodies against the PF4-heparin complex are important contributors to the pathophysiology of HIT. Patients previously exposed to heparin may have these preformed antibodies, and the addition of exogenous PF4 in the presence of heparin risks an anamnestic response and severe HIT or HIT with thrombosis. More clinical experience is required to validate the safety of PF4 for heparin reversal after CPB.[116]

Reports document attempts at using other drugs for heparin neutralization. Methylene blue, hexadimethrine, vancomycin, and heparinase I are among drugs tested for heparin neutralization.[115,117,118] None of these drugs has proved equivalent to protamine in its safety profile for reversal of heparin after CPB. One of these drugs, heparinase I, was compared with protamine in a multicenter, randomized, prospective trial; heparinase I had an inferior safety profile after reversal of heparin at the end of CPB that was a result of increased transfusion and prolonged hospital stay in the heparinase group compared with the protamine group.[118]

At this time, protamine is considered the gold standard for reversal of heparin anticoagulation. If protamine cannot be used, there are not enough data to make a recommendation regarding safety and efficacy of any of the alternative heparin reversal agents.

Class IIb Recommendation

  • 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 of Evidence C)