Hemochron Jr Research Articles

An Agreement Study Between Point-of-Care and Laboratory Activated Partial Thromboplastin Time for Anticoagulation Monitoring During Extracorporeal Membrane Oxygenation.

BackgroundLaboratory activated partial thromboplastin time (LAB-aPTT) is a widely used laboratory assay for monitoring unfractionated heparin (UFH) therapy during extracorporeal membrane oxygenation (ECMO). But LAB-aPTT is confined to a central laboratory, and the procedure is time-consuming. In comparison, point-of-care aPTT (POC-aPTT) is a convenient and quick assay, which might be a promising method for anticoagulation monitoring in ECMO. This study was aimed to evaluate the agreement between POC-aPTT (hemochron Jr. Signature instruments) and LAB-aPTT for anticoagulation monitoring in adult ECMO patients.MethodsData of ECMO-supported adult patients anticoagulated with UFH in our institute from January 2017 to December 2020 was retrospectively reviewed. POC-aPTT and LAB-aPTT results measured simultaneously were paired and included in the analysis. The correlation between POC-aPTT and LAB-aPTT was assessed using Spearman’s correlation coefficient. Bias between POC-aPTT and LAB-aPTT were described with the Bland-Altman method. Influence factors for bias were identified using multinomial logistic regression analysis.ResultsA total 286 pairs of aPTT results from 63 patients were included in the analysis. POC-aPTT and LAB-aPTT correlated weakly (r = 0.385, P < 0.001). The overall bias between POC-aPTT and LAB-aPTT was 7.78 [95%CI (−32.49, 48.05)] s. The overall bias between POC-aPTT and LAB-aPTT ratio (to normal value) was 0.54 [95%CI (−0.68, 1.76)]. A higher plasma fibrinogen level [OR 1.353 (1.057, 1.733), P = 0.017] was associated with a higher chance of POC-aPTT underestimating LAB-aPTT. While a lower plasma fibrinogen level [OR 0.809 (0.679, 0.963), P = 0.017] and lower UFH rate [OR 0.928 (0.868, 0.992), P = 0.029] were associated with a higher chance of POC-aPTT overestimating LAB-aPTT.ConclusionThe present study showed poor agreement between POC-aPTT and LAB-aPTT. POC-aPTT was not suitable for anticoagulation monitoring in adult ECMO patients.

Correlation between activated clotting time monitoring and heparin concentration measurement in a patient with antiphospholipid syndrome during cardiac valve surgery: a case report

BackgroundAnticoagulation management of patients with antiphospholipid syndrome (APS) undergoing cardiac surgery is challenging due to the prolongation of activated clotting time (ACT). Currently, no study has compared the utility of ACT monitoring using the Hemochron Jr. Signature+ and that of heparin concentration management using the Hemostasis Management System (HMS) Plus in patients with APS.Case presentationA 71-year-old woman with APS was scheduled to undergo an aortic valve replacement for aortic regurgitation. The ACT was measured using the Hemochron Jr. Signature+, and the heparin concentration was measured concurrently using the HMS Plus. ACT over 480 s corresponded to an adequate heparin concentration during cardiopulmonary bypass. The clinical course was uneventful, and no thrombotic or hemorrhagic complications were observed.ConclusionIn the present patient with APS, the Hemochron Jr. Signature+ was useful as an anticoagulation management during cardiac valve surgery.

P1056SUSTAINED LOW EFFICIENCY DIALYSIS (SLED) WITH STANDARD HEMODIALYSIS MACHINE AND CITRATE AS CIRCUIT ANTICOAGULANT IN CRITICALLY ILL PATIENTS WITH ACUTE KIDNEY INJURY

Abstract Background and Aims Sustained-Low Efficiency Dialysis (SLED) is a Renal Replacement Therapy (RRT) modality characterized by excellent efficiency and hemodynamic stability that is increasingly used in critically patients with Acute Kidney Injury (AKI). SLED can be performed with either continuous RRT or conventional hemodialysis machines. Even in the case of SLED, avoiding extracorporeal circuit clotting is a mainstay of treatment, and a rational approach to this issue is represented by regional citrate anticoagulation. The present pilot study is aimed at a preliminary evaluation of safety and efficacy of a simplified regional anticoagulation protocol based on ACD-A for SLED performed by using a conventional hemodialysis machine in critically ill patients with AKI in the ICU. Method SLED was performed for 8-12 hours (daily or every other day) with a Surdial X Nipro® hemodialysis machine, with a standard hemodialysis circuit, and a triacetate of cellulose filter (Sureflux-19L, 1.9 m2, KUF 19 ml/mmHg/h). Blood flow was set at 200 ml/min and dialysis fluid flow at 100 ml/min. The citrate was infused in pre-dilution as ACD-A solution (citrate 2.2%, 112.9 mmol/L) at rates ranging from 200 to 400 ml/h, to obtain an estimated pre-filter citrate concentration between 2 and 4 mmol/L. The treatment was monitored by serial evaluations of ionized calcium (Ca ++) and ACT (Hemochron Jr) at the following times: at the beginning of the SLED (sampling at the arterial line representative of patient’s blood), at the 2nd hour (arterial line and post-filter) and at the end of SLED (arterial line). Laboratory targets for monitoring were as follows: normal values of ACT and calcium ionized (Ca++) not less than 0.9 mmol/L in the patient blood (systemic circulation), ionized calcium values not less than 0.6 mmol/L in the post-filter blood. The blood of the extracorporeal circuit was then recalcified in the filter by dialysis fluid itself (Ca ++ 1.5 mmol/L) through Ca backfiltration. The protocol does not request routine calcium infusion to the patient until Ca++ values in the post-filter blood at the 2nd hour is &amp;lt; 0.6 mmol/L. Results A total of 41 SLED sessions were performed in 12 patients (mean age 69 + 18 SD, 7 males and 5 females, mean APACHE II 22); 6 patients were on mechanical ventilation, and 6 had severe hemodynamic instability requiring high-dose vasoactive drugs. Patients had an average fluid overload of 6 Kg, as estimated by the usual weight values reported. Average pre-SLED urea was 94 mg/dL, and 32 mg/dL at the end of treatment. Most of the sessions were completed for elapsed prescribed time. Only in three cases a premature interruption was observed for clotting of circuit or of the filter (in all cases after at least 6 hours of treatment); in one case only blood restitution was not complete. No statistically significant differences were observed between systemic ACT values during SLED as compared to baseline values of the patients. Calcium infusion (calcium gluconate at fixed rate, 5 ml/h) was started in 10 treatments (10/42, 23.8%). No new cardiac arrhythmia episode or hemorrhagic events were observed during treatments or shortly after. Conclusion Our preliminary data suggests that a simplified citrate-based SLED protocol using a conventional dialysis machine is easy and safe, also ensuring a good match between prescribed and actual dialysis dose administered.

Clinical Evaluation of Measuring the ACT during Elective Cardiac Surgery with Two Different Devices

Unfractionated heparin is the mainstay of anticoagulation during cardiac surgery on cardiopulmonary bypass (CPB) due to its low cost, quick onset, and ease of reversal. Since over 30 years, the activated clotting time (ACT) has been used to assess the level of heparin activity both before and after CPB. We compared two different methods of measuring the ACT: i-STAT, which uses amperometric detection of thrombin cleavage, and Hemochron Jr, which is based on detecting viscoelastic changes in blood. We included 402 patients from three institutions (Papworth Hospital, Cambridge, UK; Groote Schuur, Cape Town, South Africa; University Hospital Basel, Basel, Switzerland) undergoing elective cardiac surgery on CPB in our study. We analyzed duplicate samples on both devices at all standard measuring points during the procedure. The correlation coefficient between two Hemochron and two i-STAT devices was .9165 and .9857, respectively. The within-subject coefficient of variation (WSCV) ranged from 8.2 to 13.6% for the Hemochron and from 4.1 to 9.1% for the i-STAT. We found that the number of occasions where one of the duplicate readings was &gt;1,000 seconds while the other was below or close to the clinically significant threshold of 400 seconds were higher for the Hemochron. We found the i-STAT to systematically return higher measurements. We conclude that the i-STAT provides a more reliable test for heparin activity and assesses safe anticoagulation during cardiac surgery on pump. The fact the that the i-STAT reads higher than the Hemochron leads to the recommendation to validate the methods against each other before changing devices.

Reliability of a point-of-care device for international normalized ratio testing during the three surgical phases of orthotopic liver transplantation: a retrospective observational study.

To investigate the reliability of a point-of-care device, the HEMOCHRON(®) Jr. Signature, for measuring the international normalized ratio (INR) during the three surgical phases of liver transplantation. A retrospective review was performed on patients undergoing liver transplantation during July to December 2013. Thirty-one patients who had simultaneous laboratory and point-of-care INR readings from each phase of liver transplant surgery (paleohepatic, anhepatic, and neohepatic) were eligible for inclusion. Bland-Altman analysis, Spearman's rank correlation, and four quadrant plots were used to compare INR results from the point-of-care device (pocINR) with those from the laboratory (labINR). Based on the Bland-Altman analysis, mean biases (95% prediction interval) were 0.10 (0.03 to 0.17), 0.19 (0.12 to 0.27), and 0.21 (0.01 to 0.43) for the paleohepatic, anhepatic, and neohepatic phases, respectively. The pocINR device showed a systematic underestimation of the labINR. The Spearman's rank correlation coefficients (95% confidence interval [CI]) were: Ρ=0.90 (95% CI 0.80 to 0.95); Ρ=0.92 (95% CI 0.71 to 0.93); and Ρ=0.71 (95% CI 0.46 to 0.85), respectively. Direction-of-change analysis between the paleohepatic to anhepatic and the anhepatic to neohepatic phases showed strong concordance of 84% and, also considering the small bias between the measurements, supports the use of the pocINR device in the clinical management of liver transplant surgery. Point-of-care INR was accurate prior to hepatic reperfusion, but reliability decreased in the neohepatic phase.

Monitoring low molecular weight heparins at therapeutic levels: dose-responses of, and correlations and differences between aPTT, anti-factor Xa and thrombin generation assays.

BackgroundLow molecular weight heparins (LMWH’s) are used to prevent and treat thrombosis. Tests for monitoring LMWH’s include anti-factor Xa (anti-FXa), activated partial thromboplastin time (aPTT) and thrombin generation. Anti-FXa is the current gold standard despite LMWH’s varying affinities for FXa and thrombin.AimTo examine the effects of two different LMWH’s on the results of 4 different aPTT-tests, anti-FXa activity and thrombin generation and to assess the tests’ concordance.MethodEnoxaparin and tinzaparin were added ex-vivo in concentrations of 0.0, 0.5, 1.0 and 1.5 anti-FXa international units (IU)/mL, to blood from 10 volunteers. aPTT was measured using two whole blood methods (Free oscillation rheometry (FOR) and Hemochron Jr (HCJ)) and an optical plasma method using two different reagents (ActinFSL and PTT-Automat). Anti-FXa activity was quantified using a chromogenic assay. Thrombin generation (Endogenous Thrombin Potential, ETP) was measured on a Ceveron Alpha instrument using the TGA RB and more tissue-factor rich TGA RC reagents.ResultsMethods’ mean aPTT at 1.0 IU/mL LMWH varied between 54s (SD 11) and 69s (SD 14) for enoxaparin and between 101s (SD 21) and 140s (SD 28) for tinzaparin. ActinFSL gave significantly shorter aPTT results. aPTT and anti-FXa generally correlated well. ETP as measured with the TGA RC reagent but not the TGA RB reagent showed an inverse exponential relationship to the concentration of LMWH. The HCJ-aPTT results had the weakest correlation to anti-FXa and thrombin generation (Rs0.62–0.87), whereas the other aPTT methods had similar correlation coefficients (Rs0.80–0.92).ConclusionsaPTT displays a linear dose-respone to LMWH. There is variation between aPTT assays. Tinzaparin increases aPTT and decreases thrombin generation more than enoxaparin at any given level of anti-FXa activity, casting doubt on anti-FXa’s present gold standard status. Thrombin generation with tissue factor-rich activator is a promising method for monitoring LMWH’s.

Inaccuracy of Point-of-Care International Normalized Ratio in Rivaroxaban-Treated Patients

To report 2 cases in which point-of-care international normalized ratios (POC-INRs) measured using a Hemochron Jr. Signature Elite device (International Technidyne Corporation) were inaccurate in rivaroxaban-treated patients. Therapy in an 86-year-old man with atrial fibrillation was converted from warfarin to rivaroxaban 15 mg twice daily because of a deep venous thrombotic event despite an INR of 2.4, which was within the therapeutic range. One week later a POC-INR was inadvertently measured, which was 6.3. In light of the POC-INR being markedly elevated, a laboratory test for INR was performed, which gave a result of 2.74. Therapy in a 66-year-old man was converted from war-farin to rivaroxaban 15 mg twice daily because of unstable INRs and a pulmonary embolism despite a therapeutic INR. Seven days after rivaroxaban was started, the patient's POC-INR was 9.2; simultaneously measured laboratory-determined INR was 2.0. For both patients, coagulation tests performed on follow-up visits revealed continued discordance between the POC and laboratory assays. Rivaroxaban is an oral factor Xa inhibitor with a predictable pharmacokinetic profile, allowing for a fixed-dose regimen without the need for coagulation monitoring. When patients' therapy is switched from rivaroxaban to warfarin, it is recommended that the drugs be given concurrently until the INR is 2.0 or higher, to ensure adequate anticoagulation during this well-recognized vulnerable period for stroke. POC testing is a common method of INR assessment in clinical practice. During ROCKET-AF (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation), POC-INRs were measured exclusively with the INRatio device (Hemosense), and values above 4 were seen very rarely (0.25%), which indicates that the values determined in our patients were highly unusual. Our 2 patients receiving rivaroxaban had POC-INRs elevated beyond what was expected; these measurements were discordant from INRs simultaneously measured via the laboratory. A prospective evaluation assessing the accuracy of other commonly used POC-INR devices in patients receiving rivaroxaban would determine whether our findings extend to other devices. Until that time, laboratory measurement of INR or POC-INR using an INRatio device is recommended when patients' therapy is transitioned from rivaroxaban to warfarin.

Interpretation of Point-of-care INR Results in Patients Treated with Dabigatran

BackgroundPoint-of-care devices for measurement of the international normalized ratio (INR) are commonly used to monitor therapy and maintain therapeutic levels of anticoagulation in patients treated with vitamin K antagonists. Dabigatran, a new oral, reversible direct thrombin inhibitor approved for stroke prevention in patients with atrial fibrillation does not require routine coagulation monitoring. However, case reports have identified falsely elevated point-of-care INR levels in patients treated with dabigatran using one of these devices (Hemochron). This in vitro study was designed to verify this issue. MethodsWe compared INR levels in whole blood and plasma using a Hemochron Jr. Signature+ point-of-care device (International Technidyne Corporation, Edison, NJ) with routine laboratory monitoring, using blood from healthy volunteers that was spiked with increasing concentrations of dabigatran. ResultsProthrombin time and INR levels were increased about 2- to 4-fold with the point-of-care device compared with laboratory measures across the plasma dabigatran concentration range 50-1400 ng/mL. At plasma concentrations of dabigatran likely to be observed in patients, at a dose of 150 mg twice daily (60-275 ng/mL), whole blood point-of-care INR values increased from 1.7 to 4.0, versus 1.1 to 1.5 measured with the laboratory coagulometer. Similar differences in prothrombin time were observed in plasma samples. ConclusionsINR levels in patients taking dabigatran are substantially higher using a Hemochron Jr. point-of-care device compared with laboratory values. We discourage the use of these devices specifically, as well as the use of the INR in general, for measuring the anticoagulant effect of dabigatran.

Enoxaparin Anticoagulation Monitoring in the Catheterization Laboratory Using a New Bedside Test

This study evaluated the ability of the bedside test Hemochron Jr. Hemonox (International Technidyne Corporation, Edison, New Jersey) to identify patients with insufficient anti-Xa activity level in the catheterization laboratory. Inadequate anticoagulation in patients undergoing percutaneous coronary intervention (PCI) is associated with increased periprocedural ischemic events. In 296 unselected patients undergoing catheterization and/or PCI, whole blood Hemonox clotting time (CT) and activated partial thromboplastin time (aPTT) were measured at baseline (T1) and 10 min after the intravenous administration of enoxaparin (T2) in patients receiving additional enoxaparin and compared with plasma chromogenic anti-Xa activity level. Median values were 0.1 IU/ml (interquartile range [IQR]: 0.1 to 0.1 IU/ml) and 0.87 IU/ml (IQR: 0.74 to 1.03 IU/ml) for anti-Xa; 74 s (IQR: 70 to 81 s) and 143 s (IQR: 114 to 206 s) for Hemonox CT; and 44 s (IQR: 39 to 50 s) and 72 s (IQR: 58 to 93 s) for aPTT at T1 and T2, respectively. When using Hemonox CT to discriminate patients with anti-Xa level <0.5 IU/ml, the area under the receiver operating characteristic curve was 0.95 +/- 0.01 (95% confidence interval [CI]: 0.93 to 0.97) versus 0.89 +/- 0.01 (95% CI: 0.86 to 0.92) for aPTT. The threshold value of 120 s was associated with a 94.9% (95% CI: 91.1% to 97.4%) sensitivity and a 73.3% (95% CI: 67.6% to 78.5%) specificity to detect patients with inadequate anti-Xa level (<0.5 IU/ml) and positive predictive and negative predictive values of 73.9% (95% CI: 68.7% to 79.0%) and 94.78% (95% CI: 91.8% to 97.8%), respectively. Hemonox CT appears to be a fast and reliable bedside test for detecting patients insufficiently anticoagulated and needing adjustment of anticoagulation therapy with enoxaparin before PCI.

Internal quality control of prothrombin time in primary care: comparing the use of patient split samples with lyophilised control materials

Many primary care laboratories use point-of-care (POC) instruments to monitor patients on anticoagulant treatment. The internal analytical quality control of these instruments is often assessed by analysing lyophilised control materials and/or by sending patient samples to a local hospital laboratory for comparison (split sample). The aim of this study was to evaluate the utility of these two models of prothrombin time quality control. The models were evaluated by power functions created by computer simulations based on empirical data from 18 primary care laboratories using the POC instruments Thrombotrack, Coagu-Chek S, or Hemochron Jr. Signature. The control rules 1(2S), 1(3S), exponential weighted moving average, and the deviation limits of +/- 10% and +/- 20% were evaluated by their probability of error detection and false rejections. The total within-lab coefficient of variation was 3.8% and 6.9% for Thrombotrack, 8.9% and 10.5% for CoaguChek S, and 9.4% and 14.8% for Hemochron Jr. Signature for the control sample measurements and the split sample measurements, respectively. The probability of error detection was higher using a lyophilised control material than a patient split sample for all three instruments, whereas the probability of false rejection was similar. A higher probability of error detection occurred when lyophilised control material was used compared with the patient split samples; therefore, lyophilised control material should be used for internal analytical quality control of prothrombin time in primary health care.

Evaluation of the REG1 Anticoagulant System Using Thrombelastography and Thrombin Generation Assay.

Background: The REG1 system (Regado Biosciences, Inc. Durham, NC) is a novel anticoagulant system which comprises RB006 (drug) and RB007 (antidote). The aptamer, RB006 selectively binds to FIXa and blocks factor Xa generation. RB007 is a complementary ligand that selectively binds to RB006, and reverses its anticoagulant effect (1). Phase 1 testing demonstrated a clear pharmacodynamic dose response to RB006 in plasma coagulation assays (1), but further work is needed to understand the pharmacodynamic response to the REG1 system in whole blood assays. Therefore, we evaluated the effects of RB006 and RB007 alone and in combination using activated partial thromboplastin time (APTT), viscoelastic (TEG®, Haemoscope, IL) and thrombin generation assay (Thrombinoscope™, Synapse BV).Methods: After IRB approval, blood samples were collected from 4 consented healthy volunteers into 3.2% citrate tubes. For APTT and TEG testing blood was placed in thirteen 2 ml Eppendorf tubes. Tube one had 20 μl of saline added and served as a control. The remaining 12 tubes were divided into 3 groups. Group1: RB006 (final concentrations 3, 6, 12, 18 and 24 μg/ml); Group 2: RB007 (final concentrations 6, 12, 24, and 48 μg/ml) and Group 3: combination of both agents at a weight:weight ratio 2 to 1 for RB007:RB006 (final concentrations as above). All testing was performed within 3-hour of blood draw. APTT was done using Hemochron Jr® (ITC, NJ) instrument in recalcified whole blood. TEG was peformed in recalcified whole blood, 360 μl activated with 2 nM thrombin. For Thrombinoscope, whole blood was centrifuged at 2000 x g for 15 min to obtain platelet poor plasma (PPP). PPP samples were prepared to contain the same concentrations of RB006, RB007, and combination of both agents as described in whole blood samples. Thrombin generation analyses were performed using microplate format using diluted Actin (Dade Behring, Marburg, Germany) as a trigger (2).Results: RB006 dose dependently increased APTT (Table 1). Increasing concentrations of RB006 progressively prolonged onset, and decreased the rate of thrombus formation on TEG (Figure1A). On Thrombinoscope, RB006 dose dependently delayed lag time and decreased peak thrombin generation (Table 1, Figure1B). All the parameters of aPTT, TEG and thrombin generation returned back to control values when combination of aptamer-anti-aptamer was tested. RB007 alone had no effects on any of the tests performed.Conclusion: Along with conventional point of care APTT testing TEG and Thrombinoscope methodologies can be very useful in monitoring the anticoagulation effects of aptamer, RB006, and its reversal with anti-aptamer, RB007.Effects of Aptamer, RB006, on aPTT and Thrombinoscope lag time/peak thrombinRB006μg/mlAPTT secLag time minPeak thrombin nM0 (control)51.3 ± 1.010.8 ± 0.3244 ± 16.2395.3 ± 3.014.2 ± 0.9173 ± 22.96152 ± 10.018.8 ± 0.5145 ± 23.012183 ± 4.324.1 ± 1.1105 ± 11.018238 ± 15.326.3 ± 2.392.3 ± 7.324257 ± 11.331.3 ± 3.888.2 ± 8.3Data shown as mean ± SD [Display omitted]

Monitoring fondaparinux with the Sonoclot

Fondaparinux is a new anticoagulant that interacts with antithrombin III and activated coagulation factor X resulting in an inhibition of the coagulation system. It has been successful in doses of 2.5 mg for thromboprophylaxis as well as in higher therapeutic doses of 5-7.5 mg. No optimal method for monitoring the effects of fondaparinux has been proposed. The aim of the present study was to investigate whether a viscoelastic coagulation analyzer, the Sonoclot (Sienco, Denver, Colorado, USA), could be used for in-vitro monitoring of fondaparinux. Different concentrations of fondaparinux were added in vitro to whole blood taken from eight volunteers. The blood samples mixed with the various amounts of fondaparinux were analyzed using the Sonoclot. The whole-blood activated partial thromboplastin time with the Hemochron Jr (ITC, Edison, New Jersey, USA) was used as the reference coagulation analysis. All analyses were started expeditiously, within 30 s from sampling, and were performed at 37 degrees C. The values of the Sonoclot parameter clot rate, which measures the rate of fibrin formation, fibrin polymerization and platelet-fibrin interactions, were significantly correlated to increasing concentrations of fondaparinux (R = -0.90). The Sonoclot parameters of activated coagulation time, time to peak and clot retraction had weaker, but still significant, correlations to fondaparinux concentrations. At prophylactic doses (0.38 microg/ml blood) the clot rate decreased 15% compared with the initial unanticoagulated value, whereas at therapeutic doses (1.53 microg/ml blood) there was a 27% decrease. In conclusion, the Sonoclot parameter clot rate could be of clinical value to individualize the fondaparinux dosage, especially the higher, therapeutic, dosages.

Difference in examination of coagulation function in heparin anticoagulant therapy between point of care tests and automatic coagulation analyzer

To investigate the difference in coagulation screening in heparin anticoagulant therapy between dry-chemistry point of care tests (POCT) and automatic analyzer. Blood samples were collected from 44 patients with myocardial infarction or intracranial hemorrhage, 34 males aged 78 +/- 10 and 10 females aged 73 +/- 8, to undergo examination of prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), and fibrinogen (Fbg) by dry-chemistry methods with coagulation analyzers of the models CG02 and Hemochron Jr II. The levels of APTT of 30 patients were measured by the bedside with analyzers model Hemochron Jr II, after their anticoagulation samples underwent measurement of the plasma heparin activity with ACL Advance automatic coagulation analyzer; the APTT was determined with STA-R. The correlation coefficients of PT, INR, APTT, and Fbg between the CG02 and STA-R results were 0.945, 0.966, 0.662, and 0.977 respectively (all P < 0.05). However, t test showed that the levels of PT and INR between these 2 groups were not significant, and the differences in the levels of APTT and Fbg were significant (both P < 0.05). ACL Advance analyzer showed that the heparin activities of 30 samples were 172 approximately 1465 U/L, and the APTT values measured by Hemochron Jr II and STA-R were 87 s +/- 32 s and 90 s +/- 46 s (P < 0.01). Dry-chemistry POCT is not suitable to report the results of the same patient simultaneously with the automatic analyzer.

Anticoagulation monitoring during vascular surgery: accuracy of the Hemochron® low range activated clotting time (ACT-LR)

Activated clotting time (ACT) is currently used to monitor high concentrations of heparin anticoagulation. A new instrument, the Hemochron Jr Signature device, has been specifically designed to measure ACT in low-range heparin plasma concentrations (ACT-LR). The purpose of this study was to compare ACT-LR with anti-Xa activity in patients receiving low-dose i.v. heparin during vascular surgery. Thirty patients, undergoing arterial vascular surgery, were included in the study and received unfractionated heparin (initial dose 50 u kg(-1)). One hundred and thirty-two pairs of blood samples were simultaneously collected during surgery to determine ACT-LR and anti-Xa activity. Pearson correlation, Kappa test, ROC curve and a specific clinical interpretation of the correlation were performed. ACT-LR ranged from 68 to 380 s, anti-Xa activity from 0 to 1.45 u ml(-1). We observed a strong correlation between anti-Xa activity and ACT-LR (r(2)=0.87; P<0.0001). Accuracy of ACT-LR was good for anti-Xa activity up to 0.6 u ml(-1) (Kappa, 0.94; accuracy, 97%) and 0.8 u ml(-1) (Kappa, 0.79; accuracy, 90%), and poor for anti-Xa activity above 1 u ml(-1) (Kappa, 0.59). A clinical interpretation of the correlation graph found 98% of measured ACT-LR values to be accurate. Hemochron Jr Signature provides measurements of ACT-LR, which are accurate for monitoring heparin anticoagulation at anti-Xa activity below 0.8 u ml(-1).

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

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. 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. 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. 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.

The Influence of Prior Oral Anticoagulation Therapy on the Anticoagulant Effect of Low Molecular Weight Heparin.

Low Molecular Weight Heparins (LMWHs) have been suggested by the ACCP as an alternative to UFH for the anticoagulation of patients on chronic oral anticoagulation therapy (OAT) with warfarin. However, the optimal way to manage these patients remains to be established particularly for high-risk patients who require any type of general surgery or urgent invasive PCI procedures.The purpose of this study is to evaluate the LMWH point-of-care (POC) HEMONOXTM assay (Edison, NJ) in patients on chronic OAT. This clot-based test uses rTF reagents and the Hemochron Jr. Signature+ system. The Hemonox clotting time (CT) was analyzed at baseline and at peak response post enoxaparin treatment.Following IRB approval, blood samples from patients on chronic OAT (5 to 20 years, n=13) were evaluated with the Hemonox assay within 12– 18 hours of their last warfarin dose, patients were evaluated weekly for 4 –12 consecutive weeks. In vitro enoxaparin dose response was evaluated by adding 1 U/ml to blood samples obtained from the OAT patients. In supplemental clinical evaluation, 2 PCI cases on OAT were performed at Newark Beth Israel Medical Center, Newark, NJ. Patients were anticoagulated during their PCI procedure with enoxaparin at a final IV dose of 0.5 mg/kgHemonox CT baseline response was patient specific and the same response profile was obtained for each patient on OAT who underwent consecutive weekly testing. The majority of patients on OAT (9/13; 69%) exhibited elevated Hemonox baseline CT (150–350 secs) when compared to the previously reported range for PCI patients without prior OAT (baseline CT < 100 secs in 100% of cases, Mean = 71.2 ± 9.0, n= 39). Three patients on OAT (23%) showed CT≤150 secs, and only one patient (8%) yielded a baseline < 100 secs. When the blood of the patient with baseline < 100 sec (baseline value = 70 secs) was spiked in vitro with 1 U/ml enoxaparin, the Hemonox CT was 339 secs which was comparable with the peak response (386 and 308 secs; anti-Xa activity = 0.70 ± 0.01 U/ml; concentration of enoxaparin in the circulation = 0.77± 0.13) observed in the PCI patients receiving enoxaparin (0.5 mg/kg IV) and with a prior OAT who showed similar baseline values. Spiked samples from clinic patients with Hemonox baseline > 150 secs were > 700 secs.Our results demonstrate that prior to administration of LMWH, baseline monitoring may be helpful in patients on OAT to alert clinicians to appropriate alterations of enoxaparin dosing and target anticoagulation times due to the influence of warfarin.

A Novel Thrombelastograph?? Tissue Factor/Kaolin Assay of Activated Clotting Times for Monitoring Heparin Anticoagulation During Cardiopulmonary Bypass

We used a thrombelastograph (TEG) assay with tissue factor and kaolin (TEG TF/K) to measure activated clotting time (ACT) in 31 patients during cardiopulmonary bypass. For comparison, ACTs were also determined by a Hemochron Jr. Signature and a Hepcon HMS. The TEG TF/K correlated with both the Hepcon (r(2) = 0.789) and Hemochron (r(2) = 0.743) ACTs. The average ACT after heparin was 319 +/- 119 s (mean +/- sd) for the TEG TF/K compared with 624 +/- 118 s for the Hepcon instrument. To evaluate the effects of hemodilution on TEG TF/K and Hemochron assays, ACT assays were performed on blood diluted to 50% and titrated with heparin from 0 to 6 U/mL. Both instruments showed significant (P < 0.01) changes in the ACT-versus-heparin slope, but the 0 heparin intercept for the TEG TF/K ACTs was not significantly changed (P = 0.292), in contrast to that for the Hemochron device (P = 0.041). Both instruments also indicated the same 1.3:1 ratio of protamine to heparin for optimum heparin neutralization, with increasing ACTs at ratios >2.6:1. The TEG TF/K ACT assay rapidly monitors heparin anticoagulation, in addition to the capabilities of this instrument to monitor platelet function, clotting factors, and fibrinolysis.

New technology, old standards: disparate activated clotting time measurements by the Hemochron Jr compared with the standard Hemochron

Background Accurate control of the anticoagulation level is important for safe initiation of cardiopulmonary bypass. Using the Hemochron Jr., we consistently noted a higher than customary heparin dose required to achieve an activated clotting time (ACT) that, according to the literature and our quality standards, should be more than 480 seconds. This study was designed to determine whether there existed a significant difference in ACT values measured by the newer Hemochron Jr. and the older Hemochron 801 assay system. Methods A total of 30 patients underwent cardiovascular surgical procedures requiring heparinization (300 U/kg). Multiple samples for measurement of the ACT were obtained from all patients before heparinization, after heparinization, during cardiopulmonary bypass, and after protamine administration. Arterial samples were collected, and ACT was determined simultaneously on the same sample using both Hemochron Jr. and Hemochron 801. Activated clotting time data were analyzed with a linear mixed model using an unstructured variance-covariance matrix. Results Descriptive statistics on all heparinized patients revealed that the Hemochron Jr. yielded ACT results that on average were 121.28 seconds lower than the determination by the standard Hemochron 801 on the same sample of blood. This difference was −139.04 in on-pump cases and −90.51 in off-pump cases, primarily a function of the fact that higher heparin doses and therefore longer ACTs were used in patients having operations using the heart-lung machine. From the linear mixed model, the estimated average paired difference between the Hemochron Jr. and Hemochron 801 was found to be −86.03, yielding a highly significant test statistic ( t 28 = −6.18; p < 0.0001). Conclusions Lower ACT values determined by Hemochron Jr. are consistent with higher, clinically acceptable ACT values as measured by the Hemochron 801. These findings would suggest that safe levels of anticoagulation are determined in part by the specific assay used.

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.

American Heart Association/American College of Cardiology Foundation guide to warfarin therapy.

### Mechanism of Action of Coumarin Anticoagulant Drugs Warfarin, a coumarin derivative, produces an anticoagulant effect by interfering with the cyclic interconversion of vitamin K and its 2,3 epoxide (vitamin K epoxide). Vitamin K is a cofactor for the carboxylation of glutamate residues to γ-carboxyglutamates (Gla) on the N-terminal regions of vitamin K–dependent proteins (Figure 1).1–6 These proteins, which include the coagulation factors II, VII, IX, and X, require γ-carboxylation by vitamin K for biological activity. By inhibiting the vitamin K conversion cycle, warfarin induces hepatic production of partially decarboxylated proteins with reduced coagulant activity.7,8 Figure 1. The vitamin K cycle and its link to carboxylation of glutamic acid residues on vitamin K–dependent coagulation proteins. Vitamin K1 obtained from food sources is reduced to vitamin KH2 by a warfarin-resistant vitamin K reductase. Vitamin KH2 is then oxidized to vitamin K epoxide (Vit KO) in a reaction that is coupled to carboxylation of glutamic acid residues on coagulation factors. This carboxylation step renders the coagulation factors II, VII, IX, and X and the anticoagulant factors protein C and protein S functionally active. Vit KO is then reduced to Vit K1 in a reaction catalyzed by vitamin KO reductase. By inhibiting vitamin KO reductase, warfarin blocks the formation of vitamin K1 and vitamin KH2, thereby removing the substrate (vitamin KH2) for the carboxylation of glutamic acids. Vitamin K1, either given therapeutically or derived from food sources, can overcome the effect of warfarin by bypassing the warfarin-sensitive vitamin KO reductase step in the formation of vitamin KH2. Carboxylation promotes binding of the vitamin K–dependent coagulation factors to phospholipid surfaces, thereby accelerating blood coagulation.9–11 γ-Carboxylation requires the reduced form of vitamin K (vitamin KH2). Coumarins block the formation of vitamin KH2 by inhibiting the …