Comparison of activated clotting times measured using the Hemochron Jr. Signature and Medtronic ACT Plus during cardiopulmonary bypass with acute normovolemic haemodilution.

Objective This study compared the activated clotting time (ACT) measured using the Hemochron Jr. Signature (HACT) with the ACT measured using the Medtronic ACT Plus (MACT) during cardiopulmonary bypass (CPB) with acute normovolemic haemodilution (ANH) in patients undergoing cardiac surgery. Methods The ACT was checked at baseline with both devices after inducing anaesthesia, and 400 to 800 mL of whole blood was withdrawn to induce moderate ANH. Before initiating CPB, a 300-IU/kg bolus dose of heparin was administered to maintain the HACT at >400 s; protamine was later given to reverse the anticoagulation. The ACT was checked using both devices at baseline, during heparinisation, and after protamine administration. Results In total, 106 pairs of samples from 29 patients were analysed. The ACT showed a good correlation between the two devices (r = 0.956). However, Bland-Altman analysis showed that the MACT was higher, particularly at baseline and during heparinisation. Multiple regression analysis showed that the blood glucose concentration significantly influenced the differences between the two ACT devices. Conclusions The HACT was lower than the MACT during CPB with ANH in patients undergoing cardiac surgery. Clinicians should be cautious when using each ACT device within generally accepted reference ACT values.

The effects of MDCO-2010, a serine protease inhibitor, on activated clotting time in blood obtained from volunteers and cardiac surgical patients.

BACKGROUND: The activated clotting time (ACT) is widely used for monitoring heparin anticoagulation during cardiac surgery. Celite-based ACT values are prolonged when aprotinin is administered. MDCO-2010, a novel serine protease inhibitor, is currently being evaluated as a possible alternative to aprotinin. Therefore, we evaluated the in vitro effects of this novel agent on ACT values using 3 different point-of-care instruments with kaolin or celite as an activator. METHODS: The study was performed in 2 parts. In the first part, blood samples were obtained from 15 healthy volunteers. Samples were pipetted into small Eppendorf tubes and 2 concentrations of the MDCO-2010 (100 and 500 nM, final concentration) alone or with heparin (1.2 or 2.4 U/mL) were added. ACTs were measured using Helena (celite), Hemochron (kaolin), and Medtronic (kaolin) devices. In the second part of the study, blood samples were obtained intraoperatively, at 5 time points, from 15 patients undergoing cardiopulmonary bypass. MDCO-2010 at a final concentration of 100 or 500 nM was added and ACT testing was performed as before. Additional coagulation tests included prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, prothrombin, and anti-Xa levels. RESULTS: Addition of MDCO-2010 concentration-dependently prolonged ACTs in volunteers' and patients' blood samples regardless of the ACT activator or device used. In volunteer samples (no heparin) and in patient samples (baseline and intensive care unit) percent changes in ACTs due to MDCO-2010 were on average 3.1 ± 1.8 times higher (95% confidence interval 2.6-3.6; P < 0.001) for the celite-based Helena device compared with either Hemochron or Medtronic devices. CONCLUSION: MDCO-2010 causes less ACT prolongation with kaolin than with celite activation.

Multiple electrode whole blood aggregometry, PFA-100, and in vivo bleeding time for the point-of-care assessment of aspirin-induced platelet dysfunction in the preoperative setting.

BACKGROUND: Acquired platelet dysfunction due to aspirin ingestion may increase bleeding tendency during surgery. Thus, we examined the diagnostic accuracy of in vivo bleeding time (BT) and 2 platelet function assays for the preoperative assessment of a residual antiplatelet effect in patients treated with aspirin. METHODS: Consecutive patients scheduled for surgery were prospectively enrolled in this study. The patients' last aspirin ingestion had occurred within the previous 48 hours before blood sampling in the "full aspirin effect" group, between 48 and 96 hours before in the "variable aspirin effect" group, and >96 hours before in the "recovered aspirin effect" group. The control group had not taken any aspirin. Multiple electrode aggregometry, platelet function analyzer (PFA)-100, and in vivo BT were performed to assess the effects of aspirin. One-way analysis of variance on ranks with a post hoc multiple-comparison procedure (Dunn) was used to detect differences among the groups. Categorical data were compared using the z test. Receiver operating characteristic (ROC) curves were created to determine the diagnostic accuracy of the platelet function assays investigated. The area under the ROC curve (AUC), sensitivity, and specificity of the assays were calculated. The level of statistical significance was set at P < 0.05. RESULTS: Three hundred ninety-four patients were included in the analysis (133 control and 261 aspirin-treated patients). All 3 methods were able to detect the antiplatelet effect of aspirin in the full aspirin effect group. Furthermore, no difference in the measurement values between the recovered aspirin effect and control group was found, irrespective of the assay performed. Measurement values in the variable aspirin effect group were different from those of the control group in the ASPItest using multiple electrode aggregometry and COL-EPI using PFA-100 but not in BT. ROC analysis showed the highest diagnostic accuracy in excluding the residual aspirin effect in the ASPItest (AUC 0.81, P < 0.001), followed by COL-EPI (AUC 0.78, P < 0.001) and BT (AUC 0.56, P = 0.05). The cutoff value of 53 U in the ASPItest excluded the effect of aspirin with a sensitivity of 88% and specificity of 71%. CONCLUSIONS: The full therapeutic antiplatelet effects of aspirin can be expected within 48 hours of the patient's last aspirin ingestion. Platelet function recovered in our study if aspirin cessation occurred >96 hours (4 days) before; thus, in these patients, preoperative platelet function testing is not useful. To quantify any residual aspirin effect in patients who ceased their intake of aspirin between 48 and 96 hours before surgery, the ASPItest might have the highest diagnostic accuracy.

Measurement of activated coagulation time in children: evaluation of the blood-saving kaolin i-STAT activated coagulation time technique in pediatric cardiac anesthesia.

OBJECTIVE: To compare the activated coagulation times (ACTs) measured with the blood-saving kaolin i-STAT 1 ACT technique (Abbott Point of Care Inc, Princeton, NJ) with ACTs obtained from the widely used ACTR II device (Medtronic, Inc, Minneapolis, MN) in children undergoing cardiac surgery. DESIGN: A prospective, observational single-center study. PARTICIPANTS: Forty-four pediatric cardiac surgery patients. INTERVENTION: Surgery was performed with cardiopulmonary bypass (CPB) necessitating heparinization. METHODS AND MAIN RESULTS: ACTs measured on the i-STAT 1 device (2 × 95 µL) were compared with those obtained from the Medtronic ACTR II device (2 × 0.5 mL). Blood samples were drawn before, during, and after heparinization for CPB and paired for statistical analysis. The 2 techniques were compared using simple and multiregression analyses and the Bland-Altman method. In total, 179 intrarater and 142 interrater data pairs were analyzed. The intrarater reliability of the 2 devices was good, with a mean bias and limits of agreement of +2.0 and -55.5/+59.5 seconds for the Medtronic ACTR II and +0.5 and -59.9/+60.9 seconds for the i-STAT 1. An interrater reliability analysis of the mean of simultaneously measured ACT of the Medtronic ACTR II and both i-STAT 1 devices yielded a mean bias of -5.3 seconds and limits of agreement of -210.1/+199.5 seconds. A comparison of the higher of the paired ACT values from both devices showed similar results. After the removal of heparin, the i-STAT 1's ACT values became significantly lower than those measured on the Medtronic ACTR II (p < 0.001). Simple and multiregression analyses revealed that base excess independently influenced the mean bias of the ACT values from the Medtronic ACTR II (p = 0.037) and i-STAT 1 devices (p = 0.036). CONCLUSION: The kaolin i-STAT 1 ACT technique agreed well with the Medtronic ACTR II technique during the nonheparinized phase that preceded CPB. The overall agreement between the ACT obtained from the 2 devices was poor. The routine use of i-STAT 1 measured ACT values cannot be recommended as a reliable alternative to the Medtronic ACTR II.

Assessment of heparin anticoagulation by Sonoclot Analyzer in arterial reconstruction surgery.

Since heparin has been in use as an anticoagulant during vascular surgery and medical problems such as DVT or pulmonary embolism, there has been no consensus as to the best method of monitoring its effect on anticoagulation. In this study we used Sonoclot Analyzer to detect hemostasis changes resulting from heparin administration. The study involved 16 randomly selected male patients undergoing peripheral reconstructive surgery. Blood samples were drawn and analyzed in the operating room on the Sonoclot Coagulation and Platelet Function Analyzer. Results showed that patients respond to heparin differently. The Sonoclot monitors the hemodynamics of blood using four variables: SonACT (activated clotting time) time, rate, peak, and contraction rate. Heparin has three effective on the Sonoclot Signature; prolonged ACT result, lower clot rate, and reduction in clot retraction. The SonACT time is the time for first fibrin to form. Prolong this time indicates the presence of anticoagulation. The Sonoclot Analyzer results confirm that it is a reliable and sensitive device for monitoring heparinization levels.

Correlations between activated clotting time values and heparin concentration measurements in young infants undergoing cardiopulmonary bypass.

BACKGROUND: Monitoring heparin concentration along with the activated clotting time (ACT) may provide a more accurate guide for the administration of heparin to infants during cardiopulmonary bypass (CPB). However, standard laboratory assays of heparin concentration (antifactor Xa heparin concentration) require plasma instead of whole blood, and results are not immediately available to clinicians. Alternatively, measurements of whole blood heparin concentration may be performed at the bedside using an automated protamine titration device, the Hepcon instrument (Hepcon Hemostasis Management System Plus; Medtronics, Minneapolis, MN). The purpose of this investigation was to compare ACT measurements from 3 commercially available instruments and bedside measurements of whole blood heparin concentration using the Hepcon instrument with laboratory measurements of antifactor Xa plasma heparin concentration in infants younger than 6 months of age undergoing CPB. METHODS: Forty-four pediatric patients younger than 6 months of age scheduled for elective cardiac surgery requiring CPB were enrolled in this prospective study. Blood samples were drawn 3 minutes after the initial heparin bolus and immediately before the termination of CPB to obtain measurements of heparin anticoagulation. Kaolin-activated ACTs were performed with the Hemochron (International Technidyne Corporation, Edison, NJ), Hepcon, and i-STAT (i-STAT Corporation, East Windsor, NJ) instruments. Whole blood heparin concentration was measured using the Hepcon instrument. Plasma heparin concentration was measured using an antifactor Xa chromogenic substrate assay. RESULTS: Immediately after the initial heparin bolus, none of the ACT values correlated with plasma heparin concentration. When measured immediately before the termination of CPB, only the i-STAT ACT showed a moderate correlation. Conversely, bedside measurements of whole blood heparin concentration showed satisfactory agreement with laboratory measurements of plasma heparin concentration at both time points (concordance correlation coefficients 0.30 and 0.67, respectively). There is a bias in that antifactor Xa-measured plasma heparin concentration tends to be higher than Hepcon-measured whole blood heparin concentration. CONCLUSIONS: In infants younger than 6 months old undergoing CPB, caution is warranted when using ACT values as the sole indication of adequate heparin anticoagulation. In general, ACT prolongation correlates poorly with plasma heparin concentration. Only i-STAT ACT values showed a moderate correlation when measured immediately before the termination of CPB. Alternatively, bedside measurements of whole blood heparin concentration measured by the Hepcon instrument agreed well with antifactor Xa laboratory measurements. Our data support the clinical utility of bedside measurements of heparin concentration to provide timely, convenient, and accurate measurements of heparin concentration in these infants.

Does a delay in performing an activated clotting (ACT) test really matter? A study in nonheparinized blood and a single ACT machine.

Activating clotting time (ACT) is a point-of-care, blood clotting test used to monitor anticoagulation. Recently, institutional requirements have required that ACT testing be completed outside the operating room with trained, certified personnel other than anesthesia staff. For this reason, in this study, we looked at whether a delay in processing an ACT makes a significant difference to the ACT results. Twenty patients between 18 and 65 years of age consented to the study, each undergoing non-cardiac surgery, with no intraoperative administration of heparin. The study was approved by our Institutional Review Board. A blood sample was taken from the patient's arterial line in the operating room. Immediately afterward, 1 mL was placed into each of two ACT cartridges and the measurement was done in a Medtronic ACT2 machine. The first ACT value was 126.9 +/- 14.5 seconds. The ACT value at approximately 30 minutes was 108.3 +/- 20.3 seconds (p < .0001). The time between the first and last measurements was 29.4 +/- 3.0 minutes. The results suggest that the ACT values decrease over time between sampling all measurements. At approximately 30 minutes, the ACT values average 15% less than the control measurements. Therefore, it would seem prudent to determine ACT values immediately in the operating room without any delay, using point-of-care testing.

A comparison of activated coagulation time-based techniques for anticoagulation during cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: The inadequacy of heparinization during cardiopulmonary bypass (CPB) can lead to hemostatic activation with increases in postoperative blood loss and blood product requirements after cardiac surgery. Because activated coagulation time (ACT) measurements may not be accurate during CPB, the use of a heparin management system (HMS) has been advocated. This study compared the efficacy of a modified ACT-based system versus an HMS (Hepcon; Medtronic Inc, Minneapolis, MN) for CPB anticoagulation. DESIGN: Randomized controlled trial. SETTING: Regional cardiac surgery center. PARTICIPANTS: Adult elective cardiac surgical patients. INTERVENTIONS: Patients allocated to the HMS group (HC) received individualized heparin doses as indicated by the Hepcon system. Patients in the modified ACT group (C) received a standard weight-based heparin bolus with further doses as dictated by the ACT (Max-ACT, Helena Labs, Sunderland, UK). In addition, group C received supplemental heparin, independent of the ACT, as dictated by the volume of crystalloid added to the extracorporeal circuit. Outcome measures examined were hemostatic activation, postoperative chest tube loss, and blood product requirements. RESULTS: This study showed no significant difference in efficacy between the modified ACT and HMS heparinization strategies. Although the HC group received significantly greater amounts of heparin, this did not reduce hemostatic activation, postoperative blood loss, or transfusion requirements. CONCLUSION: ACT-based heparinization was found to be as efficacious as the Hepcon HMS system.

Plastic containers and the whole-blood clotting test: glass remains the best option.

This is the first study to identify normal whole-blood clotting times in various plastic containers and to identify the effect of the addition of various concentrations of Pseudechis australis (Mulga snake) venom on the clotting time in glass and plastic. Polycarbonate was identified as a potential alternative to glass as a testing container owing to a whole-blood clotting time within acceptable limits for a bedside test (mean 29.5 min) and equivalent performance to glass in the presence of P. australis venom. Other plastic containers (such as polypropylene and polyethylene) were found to be unsuitable owing to very prolonged clotting times (>60 min) or impaired performance in the presence of venom. Overall, owing to the variation between the performance of different plastics and the difficulty in differentiating between them, plastic containers cannot be recommended as an alternative to glass when performing the whole-blood clotting test for envenomed patients.

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.