The impact of heparin concentration and activated clotting time monitoring on blood conservation

Abstract

A whole blood hemostasis system (Hepcon) provides both activated clotting time and accurate whole blood heparin concentration measurements via an automated protamine titration method. This study was designed to prospectively evaluate the impact of heparin and protamine administration using this system on the incidence and treatment of bleeding after cardiopulmonary bypass. Two hundred fifty-four patients requiring cardiopulmonary bypass were enrolled in this prospective study over a 7-month period. Patients treated with antifibrinolytic agents (aprotinin, epsilon-aminocaproic or tranexamic acid) were excluded. Patients were randomly assigned to either a control (n = 127) or intervention (n = 127) group. For control patients, the anticoagulation protocol consisted of an initial fixed dose of 250 U/kg of heparin, and additional 5000 U heparin doses were administered if the activated clotting time was less than 480 seconds. Heparin was neutralized with an initial fixed dose of protamine (0.8 mg protamine per milligram total heparin). For the intervention group, an initial dose of heparin was based on an automated heparin dose-response assay. Additional heparin doses were administered if the heparin concentration was less than the reference concentration or for an activated clotting time less than 480 seconds. The protamine dose was based on the residual heparin concentration. Treatment of excessive bleeding after cardiopulmonary bypass was based on an algorithm using point-of-care testing with whole blood prothrombin time, activated partial thromboplastin time, heparinase activated clotting time, and platelet count. No differences between the two treatment groups were identified in reference to demographic factors, preoperative anticoagulant medications, preoperative coagulation data, number of reoperations, or combined procedures and duration of cardiopulmonary bypass. Indirect evidence for coagulation factor consumption was demonstrated in control patients by more prolonged whole blood prothrombin time and activated partial thromboplastin time values after cardiopulmonary bypass when compared with values obtained in the intervention group. Patients in the intervention cohort received greater doses of heparin (intervention: 612 +/- 147, control: 462 +/- 114 U/kg, p < 0.0001) and had lower protamine to heparin ratios (intervention: 0.70 +/- 0.64, control: 0.94 +/- 0.21, p = 0.0001) compared with control patients. Patients in the intervention cohort received significantly fewer platelet (intervention: 1.7 +/- 3.6 U, control: 3.7 +/- 6.7 U, p = 0.003), plasma (intervention: 0.4 +/- 1.3 U, control: 1.4 +/- 2.5 U, p = 0.0001), and cryoprecipitate units (intervention: 0.0 +/- 0.0 U, control: 0.2 +/- 1.2 U, p = 0.04) during the perioperative interval than control patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Heparin and protamine titration do not improve haemostasis in cardiac surgical patients

“…12,13 Using the RxDx system, we measured the heparin sensitivity and constructed individualised dose response curves for each patient. Heparin sensitivity was not different among the four patient groups, and the calculated dose of heparin using the titration was not different among the four groups.…”

“…Despoils et al 13 demonstrated a marginally significant reduction in postoperative bleeding and reduced transfusion of non-red blood cell components using Hepcon| (Medtronic Hemotec, Parker, CO) heparin management with a transfusion algorithm. The Hepcon differs from Hemochron| RxDx instrument in that the former measures ACT and heparin concentration via an automated protamine titration technique and calculates the heparin dose required to maintain a stable heparin concentration.…”

Un autre cœur qui saigne: une réévaluation de l’anticoagulation á l’héparine

“…Failure to consider heparin clearance during CPB can result in significantly lower heparin concentrations during CPB that may not be reflected in lower ACT values but still gives rise to subclinical thrombin generation and factor consumption. 9 Further, since reversal of UH is achieved with protamine sulphate using an approximate ratio of 1 mg protamine to 100 IU of heparin, failure to consider heparin clearance can result in administration of significantly larger dosages of protamine than required. As protamine in its own right has anticoagulant properties, 10 excess protamine can contribute to postoperative bleeding.…”

“…Primarily responsive to 'intrinsic' pathway activation, it can be confounded by the choice of activator (celite or kaolin), type of device, degree of hemodilution, extent of platelet activation, temperature of sample, concentration of aprotinin, and operator technique, even before considering actual alterations in hemostatic activity. 13 Several alternatives to simple celite or kaolin based ACT monitoring have been proposed, including targeting whole blood heparin concentration, 9 highdose thrombin time, plasma supplemented modified activated clotting time and an anti-Xa-activity-based coagulation assay. Despite the significant limitations of ACT monitoring including its lack of specificity and sensitivity, however, it remains the standard in many (most) centres where cardiac surgery is practiced.…”

“…Le fait de ne pas tenir compte de l'élimination de l'héparine pendant la CEC peut avoir pour conséquence des concentrations d'héparine nettement plus faibles durant la CEC, qui ne sont pas traduites par des valeurs plus basses de TCA mais peuvent quand même générer de la thrombine en concentration sub-clinique et la consommation de facteurs. 9 En outre, étant donné que la neutralisation de l'HNF est obtenue avec du sulfate de protamine à un ratio approximatif d'1 mg de protamine pour 100 IU d'héparine, le fait de ne pas tenir compte de l'élimination de l'héparine peut avoir comme conséquence l'administration d'une dose de protamine bien plus importante que nécessaire. La protamine présentant elle-même des propriétés anticoagulantes, 10 un excès de cette dernière peut provoquer des saignements postopératoires.…”