Hemochron Signature Research Articles

A-390 Implementation of the New GEM Hemochron 100 Point-of-care Coagulation System for Heparin Monitoring During Cardiopulmonary Bypass Procedures

Abstract Background The Ohio State University Wexner Medical Center has monitored the administration of unfractionated heparin (UFH) during cardiopulmonary bypass (CPB) procedures with the activated coagulation time test, using the Hemochron Signature Elite (Elite) instrument (Werfen) with the ACT+ cartridge. An assessment was conducted to evaluate the performance of the newest Hemochron model, the GEM Hemochron 100 (Werfen), to upgrade current instruments. Methods Precision and Methods Comparison studies were conducted with nine GEM Hemochron 100 systems. Each GEM Hemochron 100 instrument was analyzed with two levels of directCHECK liquid quality control, five replicates, over four days. The Method Comparison study compared the results from one Elite system's result, against the average result reported from one to three GEM Hemochron 100 systems. This methodology was repeated in multiple groups, using different Elite and GEM Hemochron 100 systems. All tests were performed with the ACT+ assay, which is sensitive to UFH from 1–6 IU/mL. Results Precision: All nine GEM Hemochron 100 instruments yielded: Level 1 CV ≤ 9.5%, and Level 2 CV ≤ 2.5%. Method Comparison: Total datasets 66; range 94–902 seconds; estimated bias at the 300, 420, and 480 second ACT+ clinical decision points were 1.6, 3.2, 4.1 seconds respectively; correlation (r) 0.97; slope 1.01; average CV across GEM Hemochron 100 systems 6.0%. Conclusion The performance of the new GEM Hemochron 100 system demonstrated acceptable agreement compared to the Elite system during CPB, maintaining existing ACT+ procedural target times. Results of system performance were consistent with the manufacturer's package insert, as well as previously published data. Based on the clinical performance, GEM Hemochron 100 systems have been implemented into our surgical suites.

Activated clotting time in inpatient diagnostic and interventional settings

Monitoring for the anticoagulant effect of unfractionated (UFH) at the point of care using activated clotting time in real time is vital where risk of thrombosis is high. Although monitoring UFH effect is a routine and important task, changing from one ACT instrument type or technology to another must be preceded by a clinical and statistical evaluation to determine the suitability and repeatability and establish normal and treatable ranges of this newer instrument. In this multi-center prospective evaluation we tested 1236 paired ACT+ samples, and 463 paired ACT-LR samples (1699 total) from enrolled study subjects. Clinical settings included CVOR cardiopulmonary bypass, at the beside in extracorporeal life support (ELS), the Cardiac Catheterization Lab (CCL) during diagnostic studies and percutaneous coronary interventions (PCI), interventional radiology procedures and EP interventions. This study found more consistent clinical performance from the GEM Hemochron 100 as compared to the current clinical model, the Hemochron Signature Elite. The bias of GEM Hemochron 100 for ACT+ and ACT-LR was greatest in the setting of the CVOR where ACT levels were high. ACT-LR measurements by the GEM Hemochron 100 were comparable to the SE when performed in settings of CCL, ECM, EP and ICU. Results obtained for both ACT-LR and ACT+ in all clinical settings in this study using the GEM Hemochron 100 are as accurate and more repeatable as those with the current clinically available Signature Elite.

Abstract 11378: Reference Intervals of Activated Clotting Time in Pediatric Patients Undergoing Cardiac Surgery

Introduction: Monitoring the anticoagulant effect of heparin is critical to prevent thrombosis and/or bleeding during cardiac surgery. This evaluation is usually performed by assessing the activated clotting time (ACT) with a POC device. Despite the relevance and widespread use of ACT, there are currently limited reference values to use as a target. Furthermore, compared to the adult population, infants have been described with a longer ACT, reinforcing the need to establish a separate reference interval for this segment of the population. Aim: The present work aims to propose reference intervals of ACT in pediatric patients. Methods: We collected data on 155 consecutive patients, ranging in age from 1 day to 18 years, undergoing cardiac surgery from 01-2019 to 01-2021 at Sainte-Justine hospital. Prior to surgery, patients were given UFH as a bolus of 3 mg/kg, and Hemochron Signature Elite ACT+ (Accriva Diagnostics, Inc.) was used to measure ACT before and promptly after heparin injection. Data were subsequently analyzed by using a parametric method. Lower and upper reference limits are the values at the 2.5 and 97.5 percentile, respectively. Results: The ACT before heparin injection followed a normal distribution with a lower reference limit at 85 seconds and an upper limit at 147 seconds compared to the range of 70-120 seconds proposed for the general population. Interestingly, the ACT after heparin bolus exhibited a non-gaussian distribution. Since neonates have been previously described with a greater heparin resistance compared to older infants; patients were separated into two age groups: patients < 1-month of age (Group A; n=31) and patients > 1-month (group B; n=124). Afterward, we performed a log transformation of the ACT values after heparin injection to approximate a Gaussian distribution, yielding mean ACT value of 392 seconds (limits 291-529 seconds) for Group A and 473 seconds (limits 314-996 seconds) for Group B (Welch test p value = 4.4 10 -6 ). No significant difference in ACT values prior to heparin bolus was found between the two groups. Conclusion: Overall, our results provide reference values of ACT measured using an Hemochron device, in a pediatric context, paving the way for improved patient care during cardiac surgery.

Variability of three activated clotting time point-of-care systems in cardiac surgery: reinforcing available evidence

Cardiac surgery with extracorporeal circulation (ECC) requires the administration of anticoagulant drugs to maintain ACT ranges 400-600 seconds, which requires exhaustive coagulation monitoring for which various point-of-care devices are available. However, there is variability between them, so we aimed to compare the values in ACT measurement. Simultaneous ACT measurements were performed with the Hemochron Response®, Hemostasis Management System Plus® (HMS Plus®) and Hemochron Signature® systems. A total of 255 simultaneous measurements were taken, the mean and standard deviation (SD) of each device were: Hemochron Signature® 361.1 seconds (SD: 156.9), HMS Plus® 412.8 seconds (SD: 180.9) and Hemochron Response® 422.8 seconds (SD: 187.9), being these differences statistically significant (Fridman's test p < 0.01). For comparisons the Bland-Altman method was used, resulting the Hemochron Response® has 61.7 seconds higher mean values than the Hemochron Signature®, the Hemochron Response® 10 seconds higher than the HMS Plus® and the HMS Plus® 51.7 seconds higher than the Hemochron Signature®. The differences found in comparisons are considered to be clinically relevant, which is why it is considered important to make the variability of the different monitoring systems known and to take them into account for optimal control of this parameter and its clinical repercussions.

Abstract 16805: Assessing Correlation and Agreement in Activated Clotting Time (ACT) Measurement Using Hemochron Signature Elite

Introduction &amp; Hypothesis: ACT is the preferred mode of assessing degree of anti-coagulation during cardiac catheterization. Studies have shown significant variability in ACT measurement with different company analysers. We aimed to assess correlation and agreement between two instruments of the same company, Hemochron Signature Elite. Method: Paired samples were collected before and after heparin administration for each patient. Each paired sample was collected and entered into the two instruments tagged A &amp; B using the same syringe and at the same time. Results: A total of 46 samples were included in the study. There was a significant correlation between the two instruments (r= 0.92, p- value 0.02). However, the two devices had significant discordance with a mean bias of 11.1 , 95% CI 0.77 to 24.9 and limits of agreement -35.8 to 58.1. Mean ACT between the two devices was significantly different (231 vs 248, p-value 0.01). Inter-device reliability was 30%. There was a more than 10% difference in about 30% of the paired samples and more than 20% difference in 9% of the samples. Conclusion: Significant correlation but discordance exists in ACT measurement even between the same type of device. This may affect clinical decision making during cardiac procedures and need further investigation.

Rapid Assessment of Coagulation at the Point of Care With the Hemochron Signature Elite System

Real-time point-of-care (POC) measurement of coagulation parameters, including activated clotting time (ACT), activated partial thromboplastin time, and prothrombin time with calculated international normalized ratio can improve patient outcomes in clinical settings, such as surgical and minimally invasive cardiac procedures, critical care units, and emergency departments. Point-of-care analyzers used in these settings must be small, portable, robust, and easy to use. The Hemochron Signature Elite system (Instrumentation Laboratory) offers 6 types of single-use disposable coagulation test cartridges, ACT+ (to measure high to moderate unfractionated heparin concentrations), ACT-LR (to measure moderate to low unfractionated heparin concentrations), activated partial thromboplastin time (citrate or whole-blood samples), and prothrombin time/international normalized ratio (citrate or whole-blood samples). Using a mechanical clot-detection technology, 1 to 2 drops of blood are mixed with an assay-specific reagent. Results are analyzed, displayed, and archived within minutes of testing. An integral barcode reader scans patient and operator IDs, and reagent lot details for documentation and traceability. The system supports remote connectivity (POCT01-A–compliant) and POC management of data, operators, and analyzers with GEMweb Plus 500 Custom Connectivity solution (Instrumentation Laboratory). The Hemochron Signature Elite system provides rapid and reliable testing with the broadest coagulation test menu of any POC instrument.

Transition from Hemochron Response to Hemochron Signature Elite Activated Clotting Time Devices in a Congenital Cardiac Surgery Practice

Heparin is the primary anticoagulant used during cardiac surgery to prevent thrombosis due to cardiopulmonary bypass (CPB)–related activation of the hemostatic system. The efficacy of heparin in the operating room is generally determined by activated clotting time (ACT) point-of-care tests performed throughout the procedure. In an effort to transition to the Hemochron Elite which requires approximately 1/10th the sampling volume of blood, we conducted a prospective study in 260 pediatric patients undergoing CPB. ACT tests were performed during CPB with a total of 260 pre-bypass and 1,117 on-bypass ACT values recorded. All samples were run simultaneously on both ACT devices. Several therapeutic cut-off possibilities ranging from &gt;380 to &gt;480 seconds were evaluated to ascertain the ACT level on the Elite device which best correlated with results from the Response device. Linear regression was used to determine correlation. The correlation between the two methods was moderate with a Pearsonrof .6 and .4 for pre-bypass bolus ACT values and on-bypass ACT values, respectively. As the therapeutic ACT cut-off values were lowered from 480 to 380 seconds on the Elite device relative to the Response device (&gt;480 seconds) for the on-bypass heparin samples, more patients would be under-dosed (incidence rising from 1 to 2%) and fewer patients would be overdosed (incidence decreasing from 32 to 5%) and the percent correlation between devices increased from 67 to 93%. A similar trend was observed with the pre-bypass heparin bolus samples. There was no significant effect of temperature on the ACT values comparing both devices. A therapeutic ACT value of &gt;400 seconds for CPB with the Hemochron Elite device reasonably approximates a therapeutic ACT value of &gt;480 seconds on the Hemochron Response device in our congenital cardiac surgery practice. Transitioning to the Elite device significantly reduces the overall sampling volume required for ACT monitoring during cardiac surgery.

Point-of-care measurement of activated clotting time for cardiac surgery as measured by the Hemochron signature elite and the Abbott i-STAT: agreement, concordance, and clinical reliability

BackgroundSince inadequate heparin anticoagulation and insufficient reversal can result in complications during cardiopulmonary bypass (CPB) surgery, heparin anticoagulation monitoring by point-of-care (POC) activated clotting time (ACT) measurements is essential for CPB initiation, maintainance, and anticoagulant reversal. However, concerns exist regarding reproducibility of ACT assays and comparability of devices.MethodsWe evaluated the agreement of ACT assays using four parallel measurements performed on two commonly used devices each (i.e., two Hemochron Signature Elite (Hemochron) and two Abbott i-STAT (i-STAT) devices, respectively). Blood samples from 30 patients undergoing cardiac surgery on CPB were assayed at specified steps (baseline, after heparin administration, after protamine administration) with four parallel measurements (two of each device type) using commercial Kaolin activated assays provided by the respective manufactures. Measurements were compared between identical and different device types using linear regression, Bland-Altman analyses, and calculation of Cohen’s kappa coefficient.ResultsParallel i-STAT ACTs demonstrated a good linear correlation (r = 0.985). Bias, as determined by Bland-Altman analysis, was low (− 3.8 s; 95% limits of agreement (LOA): − 77.8 -70.2 s), and Cohen’s Kappa demonstrated good agreement (kappa = 0.809). Hemochron derived ACTs demonstrated worse linear correlation (r = 0.782), larger bias with considerably broader LOA (− 13.14 s; 95%LOA:-316.3–290 s), and lesser concordance between parallel assays (kappa = 0.554). Although demonstrating a fair linear correlation (r = 0.815), parallel measurements on different ACT-devices showed large bias (−20s; 95% LOA: − 290-250 s) and little concordance (kappa = 0.368). Overall, disconcordant results according to clinically predefined target values were more frequent with the Hemochron than i-STAT. Furthermore, while discrepancies in ACT between two parallel iSTAT assays showed little or no clinical relevance, deviations from parallel Hemochron assays and iSTAT versus Hemochron measurements revealed marked and sometimes clinically critical deviations.ConclusionCurrently used ACT point-of-care devices cannot be used interchangeably. Furthermore, our data question the reliability of the Hemochron in assessing adequacy of heparin anticoagulation monitoring for CPB.

Point of Care Testing (POCT) to assess drug concentration in patients treated with non-vitamin K antagonist oral anticoagulants (NOACs)

BackgroundNon–vitamin K antagonist oral anticoagulants (NOACs) do not need routine laboratory monitoring but measurement of drug concentration is important in emergency conditions. Specific laboratory tests are not readily available or not implemented in every hospital. Point-of-Care Tests (POCT) may bridge this gap and be used as a bedside solution. ObjectivesFeasibility of POCT to assess plasma levels of dabigatran, rivaroxaban and apixaban. Patients/methodsActivated Coagulation Time-Low Range (ACT - LR) using a portable Hemochron Signature Elite for dabigatran and prothrombin time (expressed as INR) by Coaguchek XS Pro for rivaroxaban and apixaban were obtained at trough and peak in 136 consecutive patients taking NOACs (70 on dabigatran, 45 on rivaroxaban and 20 on apixaban). Using a paired study design, drug concentrations were concurrently determined by functional specific tests. Results and conclusionsThe correlation between NOACs concentration and the values obtained using the POCTs was high for dabigatran and rivaroxaban (r = 0.80 and r = 0.82, respectively) and low for apixaban (r = 0.21). ACT-LR ≤ 188 s better detected dabigatran levels ≤ 50 ng/ml, with a sensitivity of 87.5% and a specificity of 84.1%. ACT-LR values > 217 s better discriminated value of dabigatran > 200 ng/ml, with a sensitivity of 86.7% and a specificity of 81.4%. INR Coaguchek values ≤ 1.2 better identified patients with rivaroxaban values < 100 ng/ml, with sensitivity of 90%, specificity of 88.5%. This analysis was not possible for apixaban. ConclusionIn emergency situations POCT use may provide useful immediate information on dabigatran and rivaroxaban concentration.

Evaluation of point-of-care testing in critically unwell patients: comparison with clinical laboratory analysers and applicability to patients with Ebolavirus infection

Data on the performance of point-of-care (POC) or near-patient devices in the management of critically unwell patients are limited, meaning that there are demands for confirming POC test results in the routine clinical laboratory and so potentially leading to delay in treatment provision. We evaluated the performance of the i-STAT CHEM 8+ and CG4+, Hemochron Signature Elite, HemoCue Hb 201+ and WBC Diff Systems on whole blood collected from medical and surgical patients admitted to the intensive care unit at an Australian tertiary care hospital. Measurements obtained for haematology, coagulation, biochemistry and arterial blood gas parameters using POC devices were compared against clinical laboratory analysers (XE-5000, STA-R Evolution, Dimension Vista 1500 and ABL800 FLEX). Bland-Altman and Passing-Bablok regression plots were constructed to assess agreement. Good correlation was defined as a bias of <10% between the POC device and the reference method. Forty arterial blood samples were collected from 28 patients. There was good correlation demonstrated for sodium, potassium, chloride, ionised calcium, glucose, urea, haemoglobin and haematocrit values (i-STAT Chem 8+); pH, pCO(2), bicarbonate and oxygen saturation (i-STAT CG4+); haemoglobin, white cell, neutrophil count and lymphocyte counts (Hemocue); and internationalised normal ratio (INR; Hemochron Signature Elite), but not creatinine, anion gap, pO(2), base excess, lactate, eosinophil count, prothrombin and activated partial thromboplastin time. POC devices were comparable to clinical laboratory analysers in measuring the majority of haematology, biochemistry and coagulation parameters in critically unwell patients, including those with infections. These devices may be deployed at the bedside to allow 'real-time' testing to improve patient care.

Limits of agreement between measures obtained from standard laboratory and the point-of-care device Hemochron Signature Elite® during acute haemorrhage

BackgroundRapid diagnosis of coagulopathy in the bleeding patient using point-of-care (POC) devices would be ideal. The Hemochron Signature Elite® (HC®) is a POC device that determines international normalized ratio (INR) and activated partial thromboplastin time (aPTT). The aim of the study was to evaluate the agreement for INR and aPTT between the HC® and standard laboratory values in acute haemorrhage. MethodsThis was a single-centre observational prospective study including patients with acute haemorrhage. Laboratory INR and aPTT were compared with simultaneous measurements performed with the HC®. The diagnostic performance of HC® was determined; bias and limits of agreement were calculated according to the method of Bland and Altman. ResultsSeventy-two pairs of measurements from 39 patients were analysed. The bias between the INR-HC® and aPTT-HC® measurements and the central laboratory were 0.02 and −1.13, respectively. The Spearman's correlation coefficients for the INR-HC®/INR-lab and the aPTT-HC®/aPTT-lab were 0.68 and −0.29, respectively. Twenty-seven per cent of INR-HC® values and 89% of the aPTT-HC® values exceeded the predefined limits of agreement. The INR-HC® measurement identified patients with a central laboratory INR >1.5 with a sensitivity, specificity, and positive and negative predictive values of 83%, 70%, 76%, and 77%, respectively. ConclusionsThe results showed a lack of agreement between the INR-HC® and the aPTT-HC® measurements and the standard laboratory in the context of acute haemorrhage. The INR-HC® showed moderate performance as a decision-making tool to detect coagulopathy in the context of acute haemorrhage.

Relationship of Activated Clotting Time to Heparin Dose Depends on the Type of Cuvette Used With the Hemochron Signature Elite

Relationship of Activated Clotting Time to Heparin Dose Depends on the Type of Cuvette Used With the Hemochron Signature Elite

Comparison of Point-of-Care Activated Clotting Time Systems Utilized in a Single Pediatric Institution

This study compares four different activated clotting time (ACT) point-of-care (POC) testing systems used at our institution for the management of patients undergoing heparin therapy. We evaluated these systems under identical conditions to determine their accuracy, reproducibility, ease of use, and cost. Two separate testing stations containing four ACT systems were used. The testing order was randomized for every sample and performed by two trained individuals. Samples of fresh heparinized whole blood were taken at regular intervals and distributed to each station. Each operator tested 50 samples, totaling 400 ACT tests. The ACT value was significantly affected by the type of machine used at both stations 1 and 2 (p &lt; .001). Compared with all systems, the Medtronic ACT Plus Automated Coagulation Timer System (ACT Plus) resulted in the most consistent ACT values (median = 171, Interquartile Range (IQR): 169–175) and least variability (172.17 ± 5.24). The Hemochron Signature Elite Whole Blood Microcoagulation System had the most variability (221.10 ± 14.78) and yielded consistently higher ACT values (median = 220, IQR: 210–229.5) compared with other systems. The ACT values reported by the i-STAT Handheld and Test Cartridge Blood Analysis System (153.30 ± 7.87) were consistently lower (median = 154, IQR: 147–161) in comparison to the ACT Plus and Medtronic HMS Plus Hemostasis Management System (180.60 ± 7.60, median = 181, IQR: 175–186). There was no statistical difference in results between the two testing sites (p &gt; .05) or the operators (p &gt;.05). The significant finding of this study was the affect each system has on the ACT value. This investigation demonstrates the variability that exists among different ACT monitoring systems at our institution. The discrepant variation in ACT values that exists with the Hemochron system questions the reliability of its use in the management of patients undergoing heparin therapy.

Interchangeability of Activated Clotting Time Values Across Different Point-of-Care Systems

Significant variability in activated clotting time (ACT) measurement exists based on the type of point-of-care system used. We sought to determine the degree of agreement in ACT measurements by the Hemochron Response and the Hemochron Signature Elite Whole Blood coagulation systems and whether these 2 systems can be used interchangeably. We prospectively compared 126-paired samples in 77 patients undergoing percutaneous coronary intervention. ACT was measured for each sample using the Hemochron Response system with glass test tubes and the Hemochron Signature Elite system with low-range ACT cuvettes simultaneously. We used correlation and Bland-Altman analyses. Mean age of the study cohort was 67 ± 11 years, 49% were women, and 65% of measurements were made after systemic anticoagulation. There was a significant correlation between the Hemochron Response and Hemochron Signature Elite systems (r = 0.84, p <0.01). However, the mean bias for the ACT measurement was 9 seconds (95% confidence interval -69 to 86). In the therapeutic range of ACT measurements, the mean bias was 15 seconds (95% confidence interval -60 to 91). Thirty-three percent of total samples had >10% disagreement and 8% of samples had >20% disagreement in the ACTs measured with the Hemochron Response compared to the Hemochron Signature Elite. In conclusion, the Hemochron Response and Hemochron Signature Elite ACT values cannot be used interchangeably. Institutions using these 2 devices should be cognizant of this difference for ensuring patient safety.

EP42675, a New Dual Action Anticoagulant: Pharmacodynamic and Pharmacokinetic Profile, and Interactions with Acetylsalicylic Acid, Clopidogrel, and Unfractionated Heparin.

Abstract 2090Poster Board II-67EP42675 is the first representative of a new class of synthetic parenteral anticoagulants with a dual mechanism of action. EP42675 is an indirect factor Xa inhibitor (antithrombin binding pentasaccharide: fondaparinux analog) and a direct free and clot-bound thrombin (factor IIa) active site inhibitor (peptidomimetic: α-NAPAP analog). EP42675 was assessed in two phase I trials: (i) a randomized double-blind placebo-controlled single ascending dose study, where a single intravenous (IV) bolus of 1, 3, or 10 mg was administered to 3 groups of healthy male subjects (6 EP42675 and 2 matching placebo per group); (ii) a study assessing the effect of acetylsalicylic acid (ASA) plus clopidogrel, and unfractionated heparin (UFH) on pharmacokinetics (PK) and pharmacodynamics (PD) of EP42675. In this study, 24 healthy male subjects received 5 mg of EP42675 as an IV bolus on day 1, then ASA 100 mg and 75 mg clopidogrel from day 8 to 21. On day 15, they received a second IV bolus of 5 mg of EP42675 and were immediately randomized in 3 groups to receive either placebo, UFH 30 IU/Kg or UFH 60 IU/Kg, thus mimicking the rescue use of UFH in complicated percutaneous coronary interventions (PCI). EP42675 plasma concentrations were measured using anti-Xa and anti-IIa activity specific bioassays (Biomnis, France). EP42675 PD was assessed by global: thrombin generation test (TGT) and activated clotting time (ACT: ACT+ cartridge, Hemochron Signature Elite®, Gamida), and specific coagulation tests performed on a STA-R Evolution® automaton: prothrombin time (PT: Neoplastine CI plus Diagnostica Stago), activated partial thromboplastin time (aPTT: PTTA Diagnostica Stago), ecarin clotting time (ECT: Ecarine Diagnostica Stago), anti Xa activity expressed as ΔDO/min (Biophen Heparin Hyphen Biomed®), and thrombin time using purified human alpha thrombin (TT: Hemoclot Thrombin Inhibitors, Hyphen Biomed®). TGT performed on platelet poor plasma (PPP) were triggered with PPP reagent high (20 pM recombinant human tissue factor and 4 μM phospholipids, Biodis) on a Calibrated Automated Thrombogram (CAT™: Diagnostica Stago). The EP42675 plasma concentrations, measured by both anti-IIa and anti-Xa bioassays, showed a high and significant correlation (r=0.99, p<0.0001) indicating that the two active moieties of EP42675 did not dissociate. The plasma concentration versus time curves showed a marked distribution phase followed by a slow terminal phase and a less than proportional increase in exposure with increasing dose, with a half-life between 44.1 and 55.3 hours. EP42675 increased ACT, TGT lag time, TT, aPTT, PT, ECT, and anti-Xa activity. Maximum anticoagulant effect was reached within 2 minutes after bolus injection and lasted for more than 72 hours. The higher sensitivity of the TT test compared to the ECT test is explained by the higher selectivity of the EP42675 antithrombin moiety for the human alpha thrombin. A decrease in TGT endogenous thrombin potential was observed with a complete inhibition of thrombin generation at peak in the 10 mg dose group. The apparent lack of dose response at lower concentrations is likely to be due to interactions between the EP42675 antithrombin moiety with the alpha2 macroglobulin-thrombin complex. As anticipated, the co-administration of UFH induced a dose-dependent further increase in ACT, TGT lag time, TT, aPTT, PT, and anti-Xa activity, while the combination of ASA and clopidogrel did not influence the PK or PD of EP42675. The intra- and inter-subject variability was low for both PK and PD parameters. EP42675 was well tolerated. The only drug-related adverse events were mild hematoma at injection or blood sampling site in 6 subjects, mild gingival hemorrhage in 7 subjects, and mild epistaxis in one subject. No change in liver function tests was observed.These data provide useful information for designing future clinical studies with a single-dose anticoagulant treatment in patients with acute coronary syndrome undergoing PCI, and treated with various combinations of antithrombotic drugs. Disclosures:Gueret:Endotis: Research Funding. Krezel:Endotis: Employment. van Giersbergen:Endotis: Consultancy. Fuseau:Endotis: Consultancy. Neuhart:Endotis: Employment.

Frequent point of care monitoring demonstrates the safety of low intensity warfarin therapy in Asian patients with mechanical heart valve

Genetic variants of the main cytochrome P-450 (CYP) and ethnicity may influence warfarin dosing. Chinese patients are reportedly more sensitive than Caucasians to the anticoagulant effect of warfarin. The use of the Point of Care Testing (POCT) and frequent monitoring of the international normalization ratio (INR) had facilitated measurements of essential coagulation parameters of warfarin therapy. To our knowledge, POCT has not been evaluated in clinical trials that underlay ethnic differences between different geographic regions. We have conducted a multi-center prospective trial to evaluate the safety of low warfarin dose, and the role of frequent INR measurements by POCT in Chinese patients. A total of 488 patients from 11 geographically diverse hospitals in China underwent implantation with CarboMedics aortic or mitral valve prosthesis (Sulzer Medica, Austin, TX). Patients received two consecutive doses of 2.5 mg warfarin at 24 and 72 h post-surgery, followed by a daily dose to maintain INR range of 1.5–2.5. The follow-up was performed weekly or biweekly and the INR was measured on fingerstick fresh whole blood, using the HEMOCHRON Signature Microcoagulation system (ITC, NJ). The majority (99.3%) of Chinese patients who required prosthetic heart valve and warfarin therapy were \70 years old with a mean age of 45.28 ± 12. The mean follow-up duration was 86.8 ± 11.2 weeks (range 72–104 weeks). A total of 4,886 INR values were obtained with a mean INR in all 11 sites at 1.76 ± 0.50. The majority of INR values (67.8%, n = 3,312), was in therapeutic range (1.5–2.5), a moderate number was below range (26.2%, n = 1,281), whereas only 6.0% (n = 293) of INR value was above range. Mean daily maintenance dose was 2.5 ± 0.60 mg in all sites; a significant reduction from age-matched ACCP guideline for rest of the world (ROW) patients. Minor bleeding occurred in 42 cases, no patient required hospitalization. Major adverse events (4 cases) were lower than reported ROW data. The maintenance of antithrombotic efficacy with low warfarin requirement and narrow INR range in Chinese patients was independent of demographic factors and geographic locations. Frequent INR-POCT confirmed the safety of low dose warfarin requirements in Chinese patients. Monitoring by POCT may provide a mean to standardize warfarin monitoring across diverse geographic regions and therefore allow the analysis of ethnic variation in various subpopulations.

The Use of the Point of Care in Evaluating the Anticoagulation Effect of Low Molecular Weight Heparin Nadroparin during Hemodialysis.

Anticoagulation in hemodialysis is targeted to prevent the activation of coagulation during the procedure. Although unfractionated heparin (UFH) is the anticoagulant commonly used, recent studies suggested the safety and efficacy of low-molecular-weight heparin (LMWH) and possibly the most cost-effective anticoagulation for hemodialysis. The activated clotting time is usually used to monitor UFH while the chromogenic anti-Xa is the standard monitoring test for LMWH. The anti-Xa is not readily available; a bedside test may be helpful to ensure optimal anticoagulation. The objective of this study was to evaluate the utility of a whole blood (WB) point of care (POC) test, HEMONOX™ (HEMOCHRON Signature+) in measuring the anticoagulation effect of Nadroparin (FRAXIPARINE®, Sanofi, France) in normal blood samples spiked with different concentrations of Nadroparin and in clinical samples from patients during hemodialysis. Following IRB approval, Nadroparin was administered to the patients (n=11) at 56 IU/Kg 3–4 min before dialysis as a single bolus dose injected into the arterial needle pre-dialysis. Blood samples were obtained at baseline, 15 min and 2 hrs post bolus and at the end of the hemodialysis for performing the following POC tests: HEMONOX, low range activated clotting time (ACT-LR) and WB-activated partial thromboplastin time (WB-aPTT). Plasma samples were separated from each blood draw for the determination of the laboratory plasma based aPTT test (Lab-aPTT, Biomerieux France) and the anti-Xa assay (STAGO, France). In vitro analyses were performed by adding Nadroparin at increasing concentrations to fresh WB from 4 healthy donors. These samples were tested for clotting time using WB-aPTT, ACT-LR and HEMONOX. All WB-POC tests showed a linear dose response to Nadroparin in concentrations of 0–2.5 IU/ml and the overall clotting time results suggest variable levels of sensitivity to Nadroparin. The HEMONOX assay showed more sensitivity to the Nadroparin concentration with increases of 2–6 fold from baseline at LMWH levels of 1 and 1.5 IU/ml blood, compared to 1.2–1.5 and 1.5–3.0 fold for the ACT-LR and the WB-aPTT respectively. The clinical data confirmed these results and also correlated well to the anti-Xa activity levels. HEMONOX values obtained at baseline time (72–109 seconds) corresponded to undetectable anti-Xa. HEMONOX peak values obtained at 15 min post bolus, corresponded to therapeutic anti-Xa level but patients showed variable response to Nadroparin. HEMONOX clotting time (CT) at peak response suggested 3 patient subgroups with different levels of sensitivity to Nadroparin: low (range: CT 92–98 seconds and anti-Xa 0.56–1.0 U/ml), intermediate (range: CT 123–160 seconds and anti-Xa 0.90–1.37 U/ml) and high responders (range: CT 319–870 seconds and anti-Xa 1.2–1.30 U/ml). The HEMONOX test was the most sensitive indicator of Nadroparin anticoagulation when compared to POCT ACT-LR and WB-aPTT coagulation tests. The HEMONOX method showed a good correlation to the Lab-aPTT (r= 0.86, n= 36) and both methods yielded comparable correlation coefficient to anti-Xa (r= 0.71, n= 27). The results from this pilot study suggest that the WB-POC test HEMONOX is sensitive to the anticoagulant effect of Nadroparin during hemodialysis. More studies are needed to confirm the significance of these findings.

Reducing Contrast Induced Injury

Data on the performance of point-of-care (POC) or nearpatient devices in the management of critically unwell patients are limited, meaning that there are demands for confirming POC test results in the routine clinical laboratory and so potentially leading to delay in treatment provision. We evaluated the performance of the i-STAT CHEM 8+ and CG4+, Hemochron Signature Elite, HemoCue Hb 201+ and WBC Diff Systems on whole blood collected from medical and surgical patients admitted to the intensive care unit at an Australian tertiary care hospital. Measurements obtained for haematology, coagulation, biochemistry and arterial blood gas parameters using POC devices were compared against clinical laboratory analysers (XE-5000, STA-R Evolution, Dimension Vista 1500 and ABL800 FLEX). Bland–Altman and Passing–Bablok regression plots were constructed to assess agreement. Good correlation was defined as a bias of <10% between the POC device and the reference method. Forty arterial blood samples were collected from 28 patients. There was good correlation demonstrated for sodium, potassium, chloride, ionised calcium, glucose, urea, haemoglobin and haematocrit values (i-STAT Chem 8+); pH, pCO2, bicarbonate and oxygen saturation (i-STAT CG4+); haemoglobin, white cell, neutrophil count and lymphocyte counts (Hemocue); and internationalised normal ratio (INR; Hemochron Signature Elite), but not creatinine, anion gap, pO2, base excess, lactate, eosinophil count, prothrombin and activated partial thromboplastin time. POC devices were comparable to clinical laboratory analysers in measuring the majority of haematology, biochemistry and coagulation parameters in critically unwell patients, including those with infections. These devices may be deployed at the bedside to allow ‘real-time’ testing to improve patient care.

Point-of-care testing of the international normalized ratio in patients with antiphospholipid antibodies

Antiphospholipid antibodies can influence the results of clotting tests in a subset of patients, which can be a major obstacle in monitoring warfarin. The aim was to determine if point-of-care testing of the International Normalized Ratio (INR) is influenced by antiphospholipid antibodies. We compared 59 patients receiving warfarin for a diagnosis of antiphospholipid antibody syndrome (APS) to 49 patients receiving warfarin for atrial fibrillation to evaluate the consistency between INR results obtained by different methods. INR results obtained by finger stick (capillary whole-blood) and venipuncture (non-citrated and citrated whole-blood) were compared with our laboratory plasma-based prothrombin time assay. Five patients (8%) with APS and both elevated anti-beta2glycoprotein I levels and positive lupus anticoagulants had non-measurable ProTime INR results and generally higher Hemochron Signature INR results than the plasma-based method, but the corresponding chromogenic factor X results were not supratherapeutic. For the remaining patients, differences between the plasma-based INR and the point-of-care INR results ranged from 0.2 +/- 0.2 to 0.4 +/- 0.3. The differences were similar for patients with APS and atrial fibrillation for all INR comparisons with the exception of the plasma-based method compared with the ProTime, which showed a mean absolute difference of 0.4 +/- 0.3 for APS patients and of 0.2 +/- 0.2 for atrial fibrillation patients (p = 0.02). In a subset ofAPS patients, the ProTime system will not yield an INR result and the HEMochron Signature (citrate and non-citrate whole-blood) INR results will exhibit elevated INR results. For this subset of APS patients, we suggest using an alternative method to monitor warfarin.

Validation of the Hemochron Jr. Signature + Microcoagulation System and the Hemochron Configuration Manager

The Hemochron Jr. Signature + is a point-of-care (POC) coagulation device that incorporates data and quality management features most often cited by health care professionals as crucial. The Hemochron Signature + and the Hemochron Configuration Manager software were evaluated at multiple sites to assess the system's clinical utility. Clinical and laboratory evaluations were performed to ensure consistency of the target anticoagulation times with the predicate Hemochron Jr. Signature. Tests for prothrombin time and activated clotting time showed excellent correlation to the Hemochron Jr. Signature (r = 0.912 and r = 0.972 respectively). After validation testing was complete, the operators at each site completed a questionnaire ranking the Signature + operational features. Electronic and liquid quality control lockout and operator and patient identification requirements were the most desirable features. Participants at all sites noted that the data management features of the Signature + would improve regulatory compliance substantially in the POC setting. Overall, the clinical operators reported the Signature + and Hemochron Configuration Manager to be an exciting, innovative technology ideally suited for managing the expanding scope of POC testing in health care.