Abstract
Background:
Protamine sulfate is widely used to reverse heparin anticoagulation in interventional cardiology. While safe in therapeutic doses, excess protamine can cause coagulopathy, hypotension, and anaphylactoid reactions. Overdosing poses particular challenges in patients at high risk for both thrombosis and bleeding. Here, we report a rare case of protamine overdose in a patient with post-PCI right coronary artery (RCA) dissection and cardiac tamponade, illustrating the hematologic and multidisciplinary coordination required to balance bleeding and thrombosis risks.
Case Presentation:
An elderly female with coronary artery disease underwent PCI for complete RCA occlusion. During the procedure, she developed iatrogenic RCA dissection, complicated by pericardial effusion and cardiac tamponade. She received 9000 units of IV heparin and was mistakenly administered 250 mg of protamine instead of 50 mg. Patient was hypotensive and required emergent pericardial window drainage, with drain placement that yielded 50 cc of blood. She was transferred to the ICU for hemodynamic and hematologic monitoring. Despite the protamine overdose, her hemoglobin remained stable and she exhibited no evidence of active bleeding or anaphylaxis. Coagulation studies (PT, aPTT, CBC) were monitored every 6 hours. Transthoracic echocardiogram confirmed resolution of the tamponade, and the drain was removed the next day. Antiplatelet therapy (aspirin and clopidogrel), initially held due to bleeding concerns, was successfully re-initiated 24 hours post-intervention.
Discussion:
Protamine-induced coagulopathy is underrecognized in hematology but has clear implications for managing PCI patients requiring urgent antithrombotic therapy. Laboratory findings typically include prolonged aPTT, ACT, and impaired clot kinetics on TEG/ROTEM, even in the absence of overt bleeding. Protamine at supratherapeutic doses neutralizes thrombin generation, reduces fibrin polymerization, and interferes with platelet aggregation. Despite the administration of five times the intended dose, our patient remained clinically stable—highlighting the unpredictable nature of protamine toxicity and the necessity of proactive surveillance. Guidelines now recommend limiting protamine to ≤2.6 mg per 100 units of heparin to prevent platelet dysfunction and viscoelastic parameter derangement [1]. If overdose occurs, serial coagulation testing and early involvement of hematology are critical. When viscoelastic tools are available, they can guide the need for cryoprecipitate, fibrinogen concentrate, or platelet transfusions to reverse clotting dysfunction [2].
Emerging alternatives such as synthetic polycationic reversal agents (e.g., UHRA) offer heparin neutralization without impacting fibrinogen or inducing pulmonary complications, although these remain investigational [3]. In practice, prompt identification and avoidance of additional heparin or antiplatelet agents, combined with serial assessment and interdisciplinary care, form the cornerstone of management.
Conclusion:
This case underscores the importance of hematologic vigilance in the setting of protamine overdose during cardiac intervention. Accurate dosing, point-of-care coagulation assessment, and delayed—but timely—re-initiation of antiplatelet therapy can mitigate both bleeding and thrombotic risks. Hematologists should be familiar with protamine pharmacodynamics and emerging reversal strategies, as interdisciplinary collaboration is essential in navigating such high-stakes, dual-risk scenarios.
References:
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Mittermayr M, Velik-Salchner C, Stalzer B, et al. Detection of protamine and heparin after termination of cardiopulmonary bypass by thrombelastometry (ROTEM): results of a pilot study. Anesth Analg. 2009;108(3):743–750. doi:10.1213/ane.0b013e31818657a3. PMID:19224778
Kalathottukaren MT, Abraham L, Kapopara PR, et al. Alteration of blood clotting and lung damage by protamine are avoided using the heparin and polyphosphate inhibitor UHRA. Blood. 2017;129(10):1368–1379. doi:10.1182/blood-2016-10-747915. PMID:28034889
