Coagulant effects of protamine sulfate on human blood in absence of heparin
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Protamine sulfate (protamine), a low molecular weight poly-cationic amine, has been used for some time on patients undergoing cardiac operations and procedures. It is particularly used on patients who have been treated with heparin (an anticoagulant), in order to neutralize the anticoagulant effects of heparin on the person's blood. In this in vitro study, various 500 /spl mu/L one-day old citrated whole human blood samples (n=18) have been subjected to different amounts of protamine of a single concentration (10 mg/mL in saline), using 0.9% saline added to blood as control. It is known that saline, by itself, has no effect on blood clotting. After thorough mixing and incubation for 10 min. at 37/spl deg/C, the time it takes for 200 /spl mu/L of each sample to clot, in presence of 20 /spl mu/L 0.1 M CaCl/sub 2/ was measured. The results show that protamine acts as an anticoagulant in the absence of heparin. Clotting time also increases with more protamine added.Keywords:
Protamine sulfate
Clotting time
Activated clotting time
Blood clotting
Human blood
Thromboelastometry
Activated clotting time
Clotting time
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In vitro, PF4 is comparable to protamine sulfate in the neutralization of heparin, but the complexes formed with heparin are different. Even with an excess of PF4, no large PF4-heparin complexes are formed and none of the complexes are able to activate ATIII, nor do these complexes dissociate on incubation in plasma at 37 degrees C. The action of PF4 and protamine is complementary. However, excess protamine displaces PF4 or prevents its complexing with heparin. When excess protamine is used to neutralize heparin in the presence of PF4, large heparin-protamine complexes are formed incorporating PF4. In contrast to the heparin-protamine complexes formed without PF4, these do not activate ATIII nor do they dissociate on incubation. Since PF4 is liberated during ECB procedures, its contribution to the stability of heparin-protamine complexes in vivo may influence the amount of protamine needed to neutralize heparin as well as affect the reactions which have been reported on injection of protamine after ECB.
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Hemodynamic responses to intravenous protamine sulfate in 40 patients were evaluated. The dose of protamine administered was calculated as adequate to reverse residual heparin as measured by the activated clotting time (ACT). Thirty patients (n = 30) received protamine at a rate of 0.5 mg/kg/min and the remainder (n = 10) received protamine at a rate of 1 mg/kg/min. Hemodynamic measurements were made before protamine, at 5-min intervals during administration, and 5 min after completion of the infusion. No statistically significant changes in cardiac output, systemic arterial blood pressure, or vascular resistance were seen when protamine was administered to patients with good left ventricular function after cardiopulmonary bypass. However, in patients with poor left ventricular function after cardiopulmonary bypass, protamine infusion was associated with systemic vasodilation that was only partially compensated for by an increase in cardiac index, resulting in a 12% decrease in mean blood pressure (P less than 0.05). Thus protamine should be administered cautiously to patients who have poor left ventricular function after cardiopulmonary bypass.
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Cardiac index
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Abstract The cause of hypotension after reversal of heparin by protamine has not been well defined. In this study we evaluated complement activation (C3a and C4a) by the heparin‐protamine complex in 46 consecutive patients (40 received protamine sulfate to reverse heparin, and six did not) during and after coronary angiography. In patients receiving protamine sulfate, there was a significant increase in C3a over the value before protamine sulfate administration ( P <.001) or in patients who did not receive protamine sulfate ( P <.05): 807 ± 100 ng/ml vs. 274 ± 75 ng/ml. There were no significant changes in C4a after protamine sulfate administration. These results indicate that the alternate complement pathway is activated when protamine sulfate is administered after coronary angiography. This may induce hypotension as well as platelet aggregation and thrombus formation and may contribute to coronary instability. Therefore, in unstable patients, heparin reversal by protamine should not be done routinely.
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The paper presents data of a study comparing two schemes (Scheme 1: a heparin/protamine ratio of 1:2; Scheme 2: a heparin/protamine ratio of 1:3) for administering protamine sulfate to neutralize heparin in patients after extracorporeal circulation. A larger dose of protamine sulfate is shown to induce significant thrombocytic dysfunction, resulting in increased postoperative hemorrhage. To minimize protamine sulfate doses required for neutralization of the anticoagulant effect of heparin is a way of preventing these complications.
Protamine sulfate
Extracorporeal circulation
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Protamine sulfate (protamine), a low molecular weight poly-cationic amine, has been used for some time on patients undergoing cardiac operations and procedures. It is particularly used on patients who have been treated with heparin (an anticoagulant), in order to neutralize the anticoagulant effects of heparin on the person's blood. In this in vitro study, various 500 /spl mu/L one-day old citrated whole human blood samples (n=18) have been subjected to different amounts of protamine of a single concentration (10 mg/mL in saline), using 0.9% saline added to blood as control. It is known that saline, by itself, has no effect on blood clotting. After thorough mixing and incubation for 10 min. at 37/spl deg/C, the time it takes for 200 /spl mu/L of each sample to clot, in presence of 20 /spl mu/L 0.1 M CaCl/sub 2/ was measured. The results show that protamine acts as an anticoagulant in the absence of heparin. Clotting time also increases with more protamine added.
Protamine sulfate
Clotting time
Activated clotting time
Blood clotting
Human blood
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