Neutralisation of systemic anticoagulation with heparin in cardiac surgery with cardiopulmonary bypass requires protamine administration. If adequately dosed, protamine neutralises heparin and reduces the risk of postoperative bleeding. However, as its anticoagulant properties are particularly exerted in the absence of heparin, overdosing of protamine may contribute to bleeding and increased transfusion requirements. This narrative review describes the mechanisms underlying the anticoagulant properties and side-effects of protamine, and the impact of protamine dosing on the activated clotting time and point-of-care viscoelastic test results, and explains the distinct protamine dosing strategies in relation to haemostatic activation and postoperative bleeding. The available evidence suggests that protamine dosing should not exceed a protamine-to-heparin ratio of 1:1. In particular, protamine-to-heparin dosing ratios >1 are associated with more postoperative 12 h blood loss. The optimal protamine-to-heparin ratio in cardiac surgery has, however, not yet been elaborated, and may vary between 0.6 and 1.0 based on the initial heparin dose.

Anticoagulant and side-effects of protamine in cardiac surgery: a narrative review

Introduction: Unfractionated heparin is a strongly anionic anticoagulant used extensively in medicine to prevent blood clotting. In the case of an emergency bleeding in response to heparin, the protamine sulfate is administered. Despite its extensive clinical use, protamine may produce life-threatening side effects such as systemic hypotension, catastrophic pulmonary vasoconstriction or allergic reactions. Recent studies have demonstrated new organ-specific complications of the heparin reversal with protamine.Areas covered: Past and present knowledge of the mechanisms responsible for the toxicity of protamine and the most promising potential replacements of protamine in the different phases of development.Expert opinion: Despite of the low therapeutic index, protamine is the only registered antidote of heparins. The toxicology of protamine depends on a complex interaction of the high molecular weight, a cationic peptide with the surfaces of the vasculature and blood cells. The mechanisms involve m...

The toxicology of heparin reversal with protamine: past, present and future

Risk Factors for Postoperative Heart Failure in Patients Operated on for Aortic Stenosis

Long-term consequences of postoperative heart failure after surgery for aortic stenosis compared with coronary surgery.

Clinical Impact of Protamine Titration-Based Heparin Neutralization in Patients Undergoing Coronary Bypass Grafting Surgery

Objectives: Platelet dysfunction is an important cause of postoperative bleeding after cardiac surgery. Protamine is routinely used for reversal of heparin after cardiopulmonary bypass (CBP), but m ...

Protamine reduces whole blood platelet aggregation after cardiopulmonary bypass

Different characteristics of postoperative heart failure after surgery for aortic stenosis and coronary disease : implications for short-term and long-term outcome

Invited reply to dr Savage on management of life-thretening haemotysis

Abstract Objectives: Platelet dysfunction is an important cause of postoperative bleeding after cardiac surgery. Protamine is routinely used for reversal of heparin after cardiopulmonary bypass (CBP), but may affect platelet aggregation. We assessed changes in platelet function in relation to protamine administration. Design: Platelet aggregation was analyzed by impedance aggregometry before and after protamine administration in 25 adult cardiac surgery patients. Aggregation was also studied after in vitro addition of heparin and protamine. The activators adenosine diphosphate (ADP), thrombin receptor activating peptide-6 (TRAP), arachidonic acid (AA) and collagen (COL) were used. Results: Platelet aggregation was reduced by approximately 50% after in vivo protamine administration; ADP 640 ± 230 (AU*min, mean ± SD) to 250 ± 160, TRAP 939 ± 293 to 472 ± 260, AA 307 ± 238 to 159 ± 143 and COL 1022 ± 350 to 506 ± 238 (all p < 0.001). Aggregation was also reduced after in vitro addition of protamine alone with activators ADP from 518 ± 173 to 384 ± 157 AU*min p < 0.001, and AA 449 ± 311 to 340 ± 285 (p < 0.01) and protamine combined with heparin (1:1 ratio) with activators ADP to 349 ± 160 and AA to 308 ± 260 (both p < 0.001); and COL from 586 ± 180 to 455 ± 172 (p < 0.05). Conclusions: Protamine given after CPB markedly reduces platelet aggregation. Protamine added in vitro also reduces platelet aggregation, by itself or in combination with heparin.

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Protamine reduces whole blood platelet aggregation after cardiopulmonary bypass

Different characteristics of postoperative heart failure after surgery for aortic stenosis and coronary disease : implications for short-term and long-term outcome

Invited reply to dr Savage on management of life-thretening haemotysis

Protamine reduces whole blood platelet aggregation after cardiopulmonary bypass