Enoxaparin Anticoagulation Monitoring in the Catheterization Laboratory Using a New Bedside Test (original) (raw)
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Journal of Thrombosis and Thrombolysis, 2006
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 ≥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 ≥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.
Point of Care: The Journal of Near-Patient Testing & Technology, 2005
Enoxaparin is increasingly used for the anticoagulation of patients undergoing percutaneous coronary intervention (PCI) alone or in conjunction with GpIIb/IIIa platelet antagonists. The purpose of this study was to evaluate a newly developed HEMONOX pointof-care test (POCT) for monitoring the effect of enoxaparin in the presence or absence of GpIIb/IIIa antagonists during PCI. Patients received two consecutive doses of enoxaparin (total 0.5 mg/kg) separated by a 5-minute interval either alone (n = 21) or in combination with a GpIIb/IIIa inhibitor following standard practice (n = 18). POCT HEMONOX, traditional coagulation tests, and plasma anti-Xa chromogenic activity assay were performed at baseline and post bolus. HEMONOX clotting time (CT) at baseline was identical in the enoxaparin (69.0 6 8.0 seconds) and enoxaparin/GpIIb/IIIa (71.0 6 8.0 seconds) treatment groups. HEMONOX CT achieved peak value at 10 minutes post initial dose (P , 0.0001) and then decreased at sheath removal (60 minutes post bolus; P = 0.001) in the two groups. HEMONOX peak response varied among patients, ranging from 130 to 431 (enoxaparin) and 104 to 386 (enoxaparin/GpIIb/IIIa) seconds, which corresponded to therapeutic anti-Xa levels of 0.69-1.14 and 0.61-1.10 U/mL, respectively. Mean HEMONOX CT was reduced 50 seconds in the presence of GpIIb/IIIa antagonists, which was associated with a reduction of anti-Xa activity (P = 0.038) but remained within therapeutic range. GpIIb/IIIa treatment did not alter the correlation between HEMONOX CT and anti-Xa activity levels (r = 0.85 vs 0.84); eptifibatide and abciximab yielded the best correlation (r. 0.90). HEMONOX was the most sensitive monitoring POCT during PCI.
Evaluation of a novel point-of-care enoxaparin monitor with central laboratory anti-Xa levels
Thrombosis Research, 2003
Background: Measurement of enoxaparin's anticoagulant activity has been limited to specialized coagulation laboratories and has been impractical for areas needing rapid results, such as during coronary angioplasty. A new point-of-care device, RapidpointR ENOXR, was recently developed to measure clotting times with enoxaparin use. Objectives: To correlate ENOX times with anti-Xa levels among patients receiving enoxaparin. Methods: A total of 166 patients receiving enoxaparin for the prevention of deep venous thrombosis or as treatment during acute coronary syndromes or angioplasty were prospectively studied. Citrated and non-citrated whole-blood (CWB and NCWB) samples were obtained at baseline and peak enoxaparin activity. ENOX times were measured with whole-blood, and the StachromR anti-Xa assay was performed on the plasma from the remainder of the samples. The Pearson correlation coefficient was used to assess the relationship between these two assays. Results: There was a strong linear correlation between the ENOX times and the anti-Xa activities for both CWB (r = 0.89, p < 0.001) and NCWB (r = 0.82, p < 0.001) when considering all 332 samples (baseline and peak). When baseline samples were excluded, the correlation remained strong for CWB ENOX times and anti-Xa levels (r = 0.84, p < 0.001), but was only moderate for NCWB (r = 0.73, p < 0.001). A CWB ENOX time of V 160 s corresponded to anti-Xa level of V 0.5 IU/ml in 95% (188/197) of patients. A CWB ENOX time z 200 s corresponded to anti-Xa levels z 0.8 IU/ml in 96% (93/96) of patients. Conclusions: RapidpointR ENOXR times correlate strongly to anti-Xa activities measured by the StachromR Heparin Assays for citrated whole-blood samples. This novel test can be used for rapid bedside measurements of enoxaparin anticoagulant activity. D
Journal of Interventional Cardiology, 2004
To evaluate the use of citrated clotting time (CCT) during percutaneous coronary intervention (PCI) in both emergent and elective scenarios and using intravenous (IV) or subcutaneous (SC) dosing. Background: Monitoring of enoxaparin during PCI had limitations in the past due to lack of point-of-care testing. Introduction of the CCT enables the determination of the degree of anticoagulation by enoxaparin. Methods and Results: An analysis on 51 consecutive patients revealed that after three SC doses (1 mg/kg twice a day) or a single IV bolus (1 mg/kg) of enoxaparin, the CCT was consistently in the therapeutic range of ≥260 seconds (475 ± 105 and 565 ± 151 sec, respectively). Patients who received <3 SC doses of enoxaparin were subtherapeutic for PCI. A supplemental IV bolus of 0.3 mg/kg was found always to raise the CCT to therapeutic level (499 ± 178 sec). Conclusions: Enoxaparin was found to be effective and safe during PCI with low vascular complication rate (9.3%). Patients who received <3 SC doses of enoxaparin benefit most from using CCT monitoring. IV dosing consistently achieved adequate anticoagulation. (
A novel point-of-care enoxaparin monitor for use during percutaneous coronary intervention
Journal of the American College of Cardiology, 2003
The aim of this study was to discern a target range of anticoagulation for enoxaparin during percutaneous coronary intervention (PCI) as measured by the Rapidpoint ENOX (Pharmanetics Inc., Morrisville, North Carolina), a new point-of-care test. BACKGROUND In the U.S., enoxaparin has been used in only a small proportion of PCI procedures, partly because a rapid enoxaparin-specific assay was unavailable.
British Journal of Clinical Pharmacology, 2005
AimRecent studies have suggested that intravenous (i.v.) enoxaparin could be used as antithrombotic therapy in patients ongoing percutaneous coronary intervention (PCI). However, anti-Xa pharmacokinetics following different i.v. dosing regimens is not clearly established.Recent studies have suggested that intravenous (i.v.) enoxaparin could be used as antithrombotic therapy in patients ongoing percutaneous coronary intervention (PCI). However, anti-Xa pharmacokinetics following different i.v. dosing regimens is not clearly established.MethodsA population pharmacokinetic analysis was developed using anti-Xa activities measured in 546 patients who received a single 0.5 mg kg−1 i.v. dose of enoxaparin immediately before PCI. Effects of higher doses (0.75 mg kg−1 and 1 mg kg−1) and/or additional bolus after the initial administration were similarly simulated.A population pharmacokinetic analysis was developed using anti-Xa activities measured in 546 patients who received a single 0.5 mg kg−1 i.v. dose of enoxaparin immediately before PCI. Effects of higher doses (0.75 mg kg−1 and 1 mg kg−1) and/or additional bolus after the initial administration were similarly simulated.ResultsEnoxaparin anti-Xa time profiles were best described by a one-compartment model with zero-order kinetics. Mean population parameters (intersubject variability, %) were CL 1.2 l h−1 (33), V 2.9 l (30) and zero-order input 0.25 h (24). With a single bolus of 0.5 mg kg−1, the totality of the patients reached an effective anticoagulation level (anti-Xa >0.5 IU ml−1) and only 2.5% reached levels above 1.5 IU ml−1. Simulations showed that greater doses (0.75 mg kg−1 and 1 mg kg−1) prolonged the duration of anticoagulation (3.4 and 4.1 h, respectively) compared with the 0.5 mg kg−1 bolus (2.7 h) and markedly increased the proportion (48% and 79%, respectively) of patients with anti-Xa levels >1.5 IU ml−1. For delayed and/or prolonged procedures, patients could be administered a second bolus of half the initial dose in a time interval between 90 min to 2 h after in order to maintain similar anticoagulation profile levels.Enoxaparin anti-Xa time profiles were best described by a one-compartment model with zero-order kinetics. Mean population parameters (intersubject variability, %) were CL 1.2 l h−1 (33), V 2.9 l (30) and zero-order input 0.25 h (24). With a single bolus of 0.5 mg kg−1, the totality of the patients reached an effective anticoagulation level (anti-Xa >0.5 IU ml−1) and only 2.5% reached levels above 1.5 IU ml−1. Simulations showed that greater doses (0.75 mg kg−1 and 1 mg kg−1) prolonged the duration of anticoagulation (3.4 and 4.1 h, respectively) compared with the 0.5 mg kg−1 bolus (2.7 h) and markedly increased the proportion (48% and 79%, respectively) of patients with anti-Xa levels >1.5 IU ml−1. For delayed and/or prolonged procedures, patients could be administered a second bolus of half the initial dose in a time interval between 90 min to 2 h after in order to maintain similar anticoagulation profile levels.ConclusionsA single 0.5 mg kg−1 i.v. dose of enoxaparin reached anticoagulation levels adequately and should be safer compared with greater doses for anticoagulation in patients undergoing an elective PCI. An additional second bolus could be proposed in patients with delayed or prolonged procedures.A single 0.5 mg kg−1 i.v. dose of enoxaparin reached anticoagulation levels adequately and should be safer compared with greater doses for anticoagulation in patients undergoing an elective PCI. An additional second bolus could be proposed in patients with delayed or prolonged procedures.
Utility of Anti-Xa Monitoring in Children Receiving Enoxaparin for Therapeutic Anticoagulation
The Journal of Pediatric Pharmacology and Therapeutics, 2005
Although enoxaparin is used to treat thromboembolism in children, current treatment guidelines are largely extrapolated from adults. The objectives of this study were to determine: i) correlation between enoxaparin dose and anti-factor Xa (anti-Xa) level, ii) intra-patient variability, and iii) whether dose or anti-Xa level is a predictor of outcomes. A retrospective chart review was conducted on all hospitalized patients receiving enoxaparin in a tertiary care pediatric institution. Simple linear regression, coefficient of variation (CV), and Student's t-test were used to analyze the objectives. Eighty treatment courses with interpretable anti-Xa levels were analyzed. Mean patient age was 6.5 years. Mean enoxaparin dose was 1.10 mg/kg q12h. Correlation between initial dosing and anti-Xa level was poor; R 2 = 0.0307 and 0.0237 for patients > 2 months with and without cardiac or renal diseases, respectively. Four out of seven patients ≤ 2 months of age compared to 4/32 patients > 2 months had a CV > 40%. Similarly, 4/12 cardiac patients compared to 4/27 noncardiac patients had a CV > 40%. Neither dose nor anti-Xa level predicted treatment success or adverse reactions (P > .05). These results suggest a need to reexamine the use of anti-Xa levels for guiding enoxaparin therapy. Further prospective studies are warranted to clarify whether routine or selective anti-Xa monitoring should be recommended in pediatric patients.
A unique, low dose of intravenous enoxaparin in elective percutaneous coronary intervention
Journal of the American …, 2002
This study was designed to examine a unique and low dose of intravenous enoxaparin in elective percutaneous coronary intervention (PCI) that would be applicable to an unselected population regardless of age, weight, renal function, or use of glycoprotein IIb/IIIa inhibitors. BACKGROUND There is limited experience of anticoagulation using intravenous (IV) low-molecular-weight heparin in PCI, which has been obtained with high doses causing elevated anticoagulation levels and delayed sheath withdrawal. METHODS A total of 242 consecutive patients undergoing elective PCI were treated with a single IV bolus of enoxaparin (0.5 mg/kg), and 26% of patients (n ϭ 64) also received eptifibatide. Sheaths were removed immediately after the procedure in patients treated with enoxaparin only, and 4 h after the procedure in those also treated with eptifibatide. RESULTS A peak anti-Xa Ͼ0.5 IU/ml was obtained in 97.5% of the population, and 94.6% of patients had their peak anti-Xa level in the predefined target range of 0.5 to 1.5 IU/ml. Advanced age, renal failure, being overweight, and eptifibatide use did not alter the anticoagulation profile. At one-month follow-up, six patients (2.5%) had died, had a myocardial infarction, or undergone an urgent revascularization; all the patients had an anti-Xa level Ͼ0.5 IU/ml during PCI. Patients without an ischemic event and without a creatine kinase rise, but with a detectable troponin release in the next 24 h of PCI (Ͼ2 g/ml, n ϭ 21), had similar anti-Xa levels as those without troponin elevation. There were one major and three minor bleeding events that were not associated with anti-Xa overshoot. CONCLUSIONS Low-dose (0.5 mg/kg) IV enoxaparin allows a prespecified target level of anticoagulation (anti-Xa Ͼ0.5 IU/ml) in the vast majority of patients undergoing PCI, appears to be safe and effective, allows immediate sheath removal when used alone, and does not require dose adjustment when used with eptifibatide.
Anaesthesia, 2009
The purpose of this study was to validate a device designed to measure activated clotting time in low-range heparin plasma concentrations (ACT-LR) prospectively during the post-operative period of vascular surgery. Measurement of ACT-LR and activated partial thromboplastin time (APTT) were performed before heparinisation (T0) and at the end of surgery (T1). ACT-LR(T1) and DACT-LR (defined as ACT-LR(T1) -ACT-LR(T0)) were evaluated as diagnostic tests for excessive anticoagulation, defined by APTT more than twice the laboratory's normal, by Bland-Altman method and receiver operating characteristic (ROC) curves. In 103 patients, mean (SD) ACT-LR was 137 (33) s at T0 and 176 (39) s at T1. Bland-Altman graph did not show a good agreement between APTT and ACT-LR. Areas under ROC curves were 0.82 (95% CI: 0.75-0.89) and 0.87 (95% CI: 0.80-0.93) for ACT-LR(T1) and DACT-LR, respectively. Using a threshold of 32 s for DACT-LR, test sensitivity was 87% (95% CI: 81-93%), specificity was 85% (95% CI: 78-92%), positive predictive value was 90% (95% CI: 84-96%) and negative predictive value was 81% (95% CI: 73-86%). While DACT-LR may have some potential in evaluating excessive anticoagulation in vascular surgery, the poor correlation between ACT-LR and APTT does not support its routine use.