Heparin monitoring during cardiac surgery. Part 1: Validation of whole-blood heparin concentration and activated clotting time.

There is limited published data on the agreement between techniques for monitoring heparin levels. The aim of this study was to validate the Hepcon/HMS, with particular focus on the agreement with laboratory anti-Xa assay. The performances of two ACT instruments--Hemochron and HemoTec--were also evaluated, including an assessment for interchangeability. Blood samples from 42 adult cardiopulmonary bypass (CPB) patients were analysed for activated clotting time (ACT), whole-blood heparin concentration (Hepcon/HMS) and anti-factor Xa (anti-Xa) plasma heparin concentration. Agreement between measures was determined using the method of Bland and Altman. Simple analysis of agreement between the Hepcon and anti-Xa heparin revealed the Hepcon has a mean bias of -0.46 U/mL, with the limits of agreement +/- 1.12 U/mL. The comparison between ACT instruments indicated a mean difference of -96 seconds for the HemoTec, with limits of +/- 265 seconds. The Hepcon/ HMS instrument displayed satisfactory agreement with anti-Xa plasma heparin concentration, as the expected variation would not be expected to cause problems in the clinical setting. Agreement between the two measurements of ACT may be satisfactory, provided each is assigned a different target value.

Heparin monitoring during cardiac surgery. Part 2: Calculating the overestimation of heparin by the activated clotting time.

Activated clotting time (ACT) values were converted to heparin concentration, enabling an assessment of the accuracy of the ACT and a quantification of the prolongation imposed by bypass. Blood samples were obtained from 42 adult cardiopulmonary bypass (CPB) patients before and during bypass surgery. Samples were analysed for ACT (HemoTec ACT) and anti-factor Xa (anti-Xa) plasma heparin concentration. The mean heparin concentration calculated before bypass was an accurate reflection of plasma heparin; however, calculated values rose to around 170% of anti-Xa values upon connection to bypass. By adjusting for this rise, for 95% of cases the calculated heparin concentration would vary between 0.60 and 1.65 times anti-Xa values. Without accounting for artificial prolongation or individual sensitivities, the ACT may give values between 0.8 and 3.0 times that indicated by the anti-Xa assay. When both individual heparin sensitivities and the effects of bypass are considered, the ACT may provide a more suitable indication of heparin levels; however, typical use may overestimate heparin up to threefold.

Alterations to haemostasis following cardiopulmonary bypass and the relationship of these changes to neurocognitive morbidity.

Cardiopulmonary bypass (CPB) is routinely utilized to provide circulatory support during cardiac surgical procedures. The morbidity of CPB has been significantly reduced since its introduction 50 years ago; however, cerebral injury remains a potentially serious consequence of otherwise successful surgery. The risk of stroke postoperatively is approximately 1-5%. Incidence rates for neurocognitive deficit, however, vary markedly depending on the detection method, although typically it is reported in at least 50% of patients. The aetiology of this cerebral injury remains open to debate, although evidence shows that ischaemia secondary to microembolism may be the principal factor. Emboli originate from bubbles of air, atheroemboli released on aortic manipulation and thromboemboli generated as a result of haemostatic activation. Significant generation of thrombin occurs during CPB resulting in fibrin formation, although the trigger of this activation is not fully understood. Rather than originating from contact activation as previously thought, the primary trigger may be via the activated factor VII/tissue factor pathway of coagulation, with an additional role of contact activation in amplification of coagulation as well as the fibrinolytic response to CPB. Haemostatic activation is inhibited with systemic heparin therapy. The relationship between haemostatic activation and emboli formation during CPB is not known. Interventions to reduce cerebral injury in the context of cardiac surgery depend, in large part, on the minimization of emboli. This review investigates cerebral injury after cardiac surgery and evidence showing that microembolism is the principal causative agent. Fibrin emboli are postulated to be an important source of cerebral embolism. The mechanism of haemostatic activation during CPB is therefore also discussed.