Clinical correlation between a point-of-care testing system and laboratory automation for lipid profile.

BACKGROUND: We evaluated the clinical correlation between the CardioChek PA analyzer and a clinical laboratory reference method to use for screening program purposes. METHODS: Fasting blood samples were collected on 516 patients (age 20-85 y). One venous sample was collected using a serum tube for the evaluation on a COBAS reference analyzer. A second venous sample was collected in a lithium heparin tube and was evaluated on the CardioChek PA analyzer (CCPA venous). A fingerstick sample (CCPA fingerstick) was evaluated only on the CardioChek PA analyzer. Linear regression analyses were performed for each measured analyte, total cholesterol, HDL-cholesterol and triglycerides. RESULTS: The correlation between the CCPA fingerstick and CCPA venous was extremely high for HDL-C and triglycerides, and good for total cholesterol. Our results demonstrated a good clinical agreement for total cholesterol, HDL-C and triglycerides between 97.7% and 94.6% in the comparison of the CCPA to the reference analyzer. CONCLUSIONS: We identified the pre-analytic phase as an important step to guarantee the quality of results and indicate that the CardioChek PA is a reliable lipid point-of-care testing system that can be used for the application of clinical screening anywhere.

ProTime self-management yielding improvement of fluency and quality of life.

Patient self-management (PSM), as the standard of care for vitamin K-antagonist therapy management in Germany requires a detailed, point-of-care (POC) device-specific training program to ensure quality patient care. In a multi-center trial using the ProTime System (Training program plus POC device), 105 patients were enrolled to evaluate efficacy of training, knowledge retention, patient satisfaction and quality of life (QoL). Patients returned to the centers 1, 3 and 6 months after training to complete questionnaires and demonstrate INR test proficiency. Training assessment employed self-evaluation and comparison of POC results between PSM and professional operators. Patient satisfaction and QoL were assessed using a modification of the questionnaire described by Sawicki and the SF12v2 QoL Survey, respectively. Patients demonstrated statistically significant improvements in knowledge post training (p < 0.001) and retained the acquired information (p = NS vs. post-training; N = 45) after 6 months. Trained patients yielded equivalent INR results to professional operators (r = 0.92) with little or no bias across all clinic visits. Compliance with weekly testing improved from 1 to 3 months (p = 0.03), remaining at the required weekly frequency through 6 months. Average patient satisfaction improved significantly during the first month and remained constant thereafter. There was a statistically significant improvement in the Physical Component Summary of SF12 between baseline and 3/6 month assessments in all centers. In conclusion, PSM requires a comprehensive system including appropriate disease and POC device training. Such a system fosters compliance, improved knowledge about underlying disease, patient satisfaction and QoL.

Executive summary. The National Academy of Clinical Biochemistry Laboratory Medicine Practice Guideline: evidence-based practice for point-of-care testing.

BACKGROUND: Point-of-care testing (POCT) is clinical laboratory testing conducted close to the site of patient care. POCT has the potential to provide faster test results and therapeutic intervention with improved patient outcomes. However, when over-utilized or used inappropriately POCT results can be misleading and increase healthcare costs. METHODS: The National Academy of Clinical Biochemistry developed evidence-based Laboratory Medicine Practice Guidelines for POCT. RESULTS: These Laboratory Medicine Practice Guidelines systematically review the scientific literature relating POCT to clinical outcomes and offer recommendations to improve the clinical utility of POCT. CONCLUSIONS: These guidelines will be useful to clinicians considering the addition of POCT, to those that question current practices in POCT, and to clinicians seeking evidence-based support for POCT in clinical management. These guidelines represent the most comprehensive systematic review of the POCT literature to date and will help define future research that is needed to add to our current POCT knowledge base.

The use of a HEMOCHRON JR. HEMONOX point of care test in monitoring the anticoagulant effects of enoxaparin during interventional coronary procedures.

BACKGROUND: Enoxaparin is increasingly used for the anticoagulation of patients undergoing percutaneous coronary intervention (PCI). Several reports have suggested the utility of using point of care tests in monitoring the anticoagulation levels of enoxaparin in patients undergoing PCI. The objective of this study was to evaluate a new point-of-care test (POCT) HEMONOX in monitoring the anticoagulant effect of enoxaparin in non citrated fresh whole blood samples from patients undergoing elective PCI procedure. METHODS: Following IRB approval, blood samples were obtained from fifty-four patients who received two sequential intravenous doses of enoxaparin; 0.1 mg/kg followed 5 min later by 0.4 mg/kg for a total of 0.5 mg/kg. Blood was drawn at baseline and at 5, 10, 30 and 60 min post first bolus for evaluation in the clot-based POCT HEMONOX, ACT and aPTT and the chromogenic anti-Xa activity assay. RESULTS: HEMONOX clotting time (CT) at baseline was 62.6 +/- 6.2 secs, (n = 32) in healthy donors and statistically higher in PCI patients (71.6 +/- 9.1 secs, p = 0.0001). The peak HEMONOX response that was always achieved at 10 min post bolus was >100 secs in all 54 patients, of these 83% yielded CT >150 secs (range: 150-466). There was no detectable anti-Xa activity level at baseline while peak HEMONOX CT corresponded to therapeutic levels (0.85 +/- 0.14 U/ml; range: 0.61-1.34). Both HEMONOX CT and anti-Xa level significantly decreased at the time of sheath removal. HEMONOX CT at peak response suggested 3 patient subgroups with different levels of sensitivity to enoxaparin: low, intermediate and high responders. The correlation between anti-Xa activity level and HEMONOX CT was >or=0.85 in each patient subgroup when data from the 3 critical time points; baseline (absence of drug), peak response (10 min post bolus) and sheath removal (60 min post bolus) were analyzed. The correlation diminished to >or=0.83 when the analyses included data from all 5 time points [baseline, 5, 10, 30, and 60 min post bolus]. The HEMONOX test was the most sensitive POCT to measure the anticoagulant effects of enoxaparin. All patients completed PCI successfully. CONCLUSION: The HEMONOX test may be able to guide anticoagulation with enoxaparin during PCI. The HEMONOX assay is a one step whole blood coagulation test performed on the HEMOCHRON Jr. Signature + POC system. The method was evaluated to monitor the anticoagulant level of enoxaparin in blood samples from patients undergoing PCI after receiving an intravenous dose of 0.5 mg/kg. The results suggest a clear distinction of HEMONOX CT between the baseline value of untreated patients and patients achieving therapeutic enoxaparin levels.

Optimizing management of hirudin anticoagulation.

Accurate anticoagulation monitoring, critical during cardiac surgery (CS), is especially important for novel therapeutics such as hirudins, for which there are no known antidotes. The activated clotting time (ACT), which is standard for heparin monitoring, has been reported to be insufficiently sensitive to high levels of hirudins. A simple, accurate, and sensitive assay is needed to monitor hirudins at the levels required for CS. During the REPLACE/II clinical trials, the HEMOCHRON Jr. Signature ACT+ was used to monitor Angiomax during percutaneous cardiac intervention (PCI) procedures and was observed to lose sensitivity at bivalirudin concentrations greater than 8-10 microg/mL. A new assay, the ACTT, was developed to increase the linear sensitivity of the ACT+ over the range of 15-30 microg/mL bivalirudin to extend the clinical utility of the assay to CS levels. Both in vitro and ex vivo studies were performed using the ACTT and ACT+. In vitro ACT+ and ACTT clotting times, identical for bivalirudin levels up to approximately 5 microg/mL, diverged from each other near 10 microg/mL. The ACTT showed excellent linearity to bivalirudin at concentrations up to 30 microg/ mL. Reproducibility was also superior with coefficients of variation <15% across 13 donors at clotting times <760 seconds. The ACTT was evaluated for monitoring bivalirudin during PCI in 67 patients. The ex vivo comparison of ACTT to ACT+ <340 seconds, showed a slope near 1.0 and an average difference between the tests of 5%. At higher clotting times this slope increased to near 3.0, with an average difference between tests of 20%. These data suggest that the ACTT displays increased sensitivity to high levels of bivalirudin.

Sensitivity of a modified ACT test to levels of bivalirudin used during cardiac surgery.

Assessment of anticoagulation status during cardiac surgery can be valuable for novel therapeutics, including direct thrombin inhibitors. The ecarin clotting time (ECT) has been reported to be sensitive for monitoring of bivalirudin in cardiac surgery but is not commercially available. The activated clotting time (ACT), commonly used for heparin monitoring, may display a lack of sensitivity to alternative anticoagulants when used in on-pump cardiac surgery. Both the ACT and ECT have been successfully used for monitoring bivalirudin anticoagulation in off-pump cardiac surgery. A new ACT, the ACTT, was developed to increase the linearity of the clotting time response to bivalirudin at higher concentrations. After Ethics Committee approval, a pilot study was performed to evaluate the feasibility of using bivalirudin for on-pump cardiac surgery and to evaluate dosing of bivalirudin in terms of the pharmacokinetic and safety profile in patients undergoing coronary artery bypass graft (CABG) surgery. Secondary objectives included an assessment of the anticoagulation profile and correlation of the response seen with various ACTs and the ECT with the plasma bivalirudin concentration in the patients' blood. After informed consent, 10 sequential patients presenting for elective cardiac surgery requiring cardiopulmonary bypass received bivalirudin anticoagulation in lieu of heparin. Dosing was fixed (1.0 mg/kg bolus followed by a 2.5 mg/kg/h infusion) and not titrated on the basis of coagulation test results. At baseline and 15-minute intervals, blood samples were collected for ACT (ACTT, Celite, kaolin, ACT+), ECT, and bivalirudin plasma level measurements. Over the range of bivalirudin plasma concentrations in this study, all clot-based systems examined were prolonged according to concentration and showed good correlation with bivalirudin plasma levels. The ACTT and the ECT showed greater sensitivity to bivalirudin (-28.5 sec/microg/ml bivalirudin) compared with the other ACTs evaluated (approximately 14 sec/microg/ml). This difference in sensitivity was also evident at low concentrations of bivalirudin (<10 microg/ ml), with the ECT and ACTT showing slopes near 40, and the ACT slopes varying from 18 to 27 sec/microg/ml. The ACTT assay is sensitive to levels of bivalirudin and may offer a simple method for monitoring bivalirudin during cardiac surgery.

The Hemochron Response RxDx heparin and protamine dosing system.

The use of dosing assays to calculate heparin and protamine dose requirements during cardiac surgery has been shown to significantly improve overall postoperative patient outcome. When patients are managed with an individualized dosing system, intraoperative and postoperative transfusion requirements and bleeding are reduced. The Hemochron RxDx system is widely used as a complement to traditional activated clotting time testing to optimize anticoagulation management. The system consists of the heparin response test, the protamine response test, and the protamine dose assay. All are modifications of the activated clotting time using either Celite (Celite Corporation, Santa Barbara, CA) or kaolin as the activator. Dosing is calculated manually using earlier version Hemochron instruments (model 801) or automatically with the Hemochron 8000 or with the early versions of the Hemochron Response and the personal digital assistant (PDA) RxDx calculator. Missing from available user options is an automated RxDx system for the Response. A study was conducted at four clinical sites to compare recently developed Response RxDx software, which eliminates the need for the PDA RxDx calculator, to the existing Hemochron 8000 RxDx and to the Response-PDA RxDx systems. Similar to the current system, the operator inputs the patient's height, weight, and gender, and the software automatically calculates the blood volume. Using the clotting times determined on the Response, bolus heparin and protamine doses and any additional heparin and protamine requirements are calculated automatically. Data were collected from 76 patients, of which, 64 patients were on pump, 11 patients were off pump, and 1 patient was converted from off to on pump. The Response estimated blood volume calculations showed a correlation coefficient of 0.989 when compared with available systems. A good correlation was also observed for the bolus heparin (r = 0.925) and protamine doses (r = 0.900) with equivalence confirmed by a paired student's t test. These data confirm that the Response RxDx system yields results that are identical (P > 0.05) to those obtained using the Hemochron 8000 RxDx or Response-PDA RxDx calculator. The Response RxDx also offers expanded user options related to blood volume limits, expanded clotting time ranges for presetting default values, and flexibility in test sequence. Case records can be printed or downloaded to a PC via the HRDM data management program. The Hemochron Response RxDx represents a complete anticoagulation management system for the cardiac surgical patient.

Racial and ethnic differences in warfarin response.

BACKGROUND AND AIM OF THE STUDY: Variability of drug response among individuals is a well-recognized problem that may result in either under- or overtreatment of patients receiving similar drug concentrations. Patients with mechanical heart valves are dependent on adequate anticoagulation to prevent thrombosis development. 'Crystalline warfarin sodium' (warfarin) is the most common antithrombotic drug prescribed to control blood hemostasis in those patients, and also in those with indications such as stroke, myocardial infarction, pulmonary embolism and atrial fibrillation. Warfarin is a narrow therapeutic index agent; a small change in systemic concentration of the drug may lead to significant changes in pharmacodynamic response. Careful clinical management is required to balance the risks of bleeding (over-anticoagulation) with those of thrombosis (under-anticoagulation). The study aim was to summarize environmental, genetic and ethnic factors that affect a patient's response to warfarin and which must be considered for optimal patient outcome. METHODS: A Medline search was carried out to summarize various factors that influence a patient's response to warfarin. RESULTS: Inter-ethnic differences may have profound implications for the efficacy and safety of warfarin. Ethnic differences can affect pharmacokinetic features such as bioavailability, protein binding and volume of distribution, as well as hepatic metabolism and renal elimination. Environmental factors and genetic variants in human enzymes that metabolize warfarin also contribute to interindividual variations and may render some patients more susceptible to serious or life-threatening adverse events. CONCLUSION: Warfarin use is complicated by an unpredictable dose response that depends on factors such as demographics, diet, interacting drugs, genetic polymorphism and ethnic differences. The impact of racial differences on the kinetics of dose response or on drug efficacy is not well defined, as few clinical trials take ethnic variation into account. The use of the point of care and frequent patient self-testing may permit standardized warfarin monitoring across diverse geographical regions and facilitate analysis of ethnic variation among subpopulations.

Hand-held personal digital assistant program for the HEMOCHRON RxDx heparin and protamine dosing system.

The use of in vitro dosing assays for heparin and protamine during cardiac surgery has significantly improved overall postoperative patient outcome. The HEMOCHRON RxDx system (International Technidyne Corp, Edison, NJ) is widely used for anticoagulation management. Based on a series of consecutive in vitro tests, the RxDx system is used to quantify the patient's heparin requirement (heparin response test, HRT), measure the activated clotting time (ACT), calculate the blood heparin concentration and the required protamine dose (protamine response test, PRT), as well as determine the efficacy of heparin reversal (protamine dose assay, PDA-O). A hand-held personal digital assistant (PDA) program has been developed that performs the RxDx calculations used for anticoagulation management during cardiac surgery. The Palm m505 hand-held device (Palm, Inc., Santa Clara, CA) is used in concert with any standard Hemochron blood coagulation system. The Palm m505 device has been programmed to perform all the calculations required for the RxDx test system. Patient's body weight, height, and gender are entered into the program using the onscreen keypad and the template provided in the Hemochron program. The calculator automatically provides the patient's blood volume and the recommended heparin dose upon entering the baseline ACT and HRT values and a target ACT. At the end of the case, the optimal protamine dose is determined, and the total heparin level is calculated and displayed upon entry of ACT and PRT clotting times. Following protamine administration, the program calculates any additional protamine required to neutralize residual heparin using the data from a PDA-O test. The RxDx hand-held PDA is accurate, quick, simple, and easy to use, patient data are saved and can be retrieved. The inclusion of this rapid computing technology into the Hemochron RxDx system serves to expand the applications of the Hemochron RxDx system during cardiac interventions.

Validation of a new whole blood coagulation monitoring system.

The Hemochron Response is a third generation point-of-care (POC) whole blood coagulation analyzer that retains the clinical utility of the Hemochron standard (801/8000) while providing a data management program that assists the POC coordinator with Quality Assurance (QA) compliance. Clinical and laboratory studies were performed to ensure consistency of the target anticoagulation times with the Hemochron standard and to evaluate precision and reproducibility of the Hemochron Response. Clinical tests for prothrombin time (PT) using fresh and citrated whole blood, activated clotting time (ACT), and activated partial thromboplastin time (APTT) showed excellent correlation to the Hemochron standard where r = 0.929, r = 0.969, r = 0.947, and r = 0.992, respectively. This was confirmed by a paired Student's t-test. The standard expectation for reproducibility of ACT tests has been a coefficient of variation (CV) of 10%. Laboratory studies of reproducibility and precision for the Response instrument included analysis of the CV using ACT test tubes. For normal and abnormal control plasma (CPL), the range of CVs observed was 3.3%-4.6% and 3.0%-5.0%, respectively. For heparin dose response analysis, the range for Donor 1 and 2 was 1.0%-4.2% and 1.1%-8.0%, respectively. These data suggest that the Hemochron Response is reliable and equivalent to the Hemochron standard in clinical applications.