The Anticoagulant Effect of Protamine Sulfate Is Attenuated in the Presence of Platelets or Elevated Factor VIII Concentrations

Abstract

We demonstrated that protamine affects the propagation of thrombin generation, which is partially reversed by platelets or increased factor VIII/von Willebrand factor concentrations. The present data suggest that excess protamine might potentially increase bleeding in the case of severe thrombocytopenia or low factor VIII.

The effects of protamine sulfate on clot formation time and clot strength thromboelastography variables for canine blood samples

“…In platelet-rich plasma, the effects of protamine on thrombin may be attenuated by platelets. 37 Such attenuation of the effects of protamine by platelets may be a reason for the less substantial thromboelastography coagulation effects detected in blood samples in the present study, compared with those detected in human plasma samples in another study. 9 Although further studies are warranted, the interaction of protamine with platelets likely decreases platelet function and the effectiveness of platelets during clot formation.…”

Carbon Monoxide Releasing Molecule-2 Improves Protamine-Mediated Hypocoagulation/Hyperfibrinolysis in Human Plasma In Vitro

“…While careful monitoring with activated clotting time using protamine titration/heparinase methodologies may diminish the threat of residual circulating heparin to post-bypass bleeding, there is still no point of care methodology to assess protamine concentration. This is important, as the concentrations of protamine used in the present and other investigations [2][3][4][5][6]9] have been observed in plasma obtained from patients following administration of 250 mg of protamine over 5 min after termination of CPB [25]. These circulating concentrations of protamine varied from 10 to 50 mg/mL, and halflife was on average 4.5 min with a range of 1.9 to 18 min noted [25].…”

“…Thus, it has been proposed that enhancement of thrombin generation may attenuate protaminemediated coagulopathy, most recently by addition of activated factor VII or factor VIII concentrate [9]. A complimentary or perhaps alternative approach would be systemic or topical administration of CORM-2, which would enhance the velocity of clot growth and strength with whatever regional thrombin generation is present.…”

“…Protamine-mediated anticoagulation also has been demonstrated in canine [7] and murine [8] models in vivo. While a definitive study implicating protamine as a source of post cardiopulmonary bypass bleeding has yet to be performed, enhancement of thrombin generation via either tissue factor [4,9] or contact protein [9] activated coagulation pathways have attenuated protamine-mediated hypocoagulation/hyperfibrinolysis in vitro.…”

Bleeding and Thrombotic Emergencies in Pediatric Cardiac Intensive Care

“…In giving protamine, the phrase ''Less is more'' is operative, since excess protamine is clearly detrimental to platelet function by nature of its inhibitory effects on the platelet receptor GPIb/IX/V interaction with vonWillebrand factor (vWF; a critical component of platelet adhesion and aggregation). 35 This effect is particularly problematic in the setting of thrombocytopenia, which is quite commonly present in patients after CPB.…”