El Rouby Soumaya, Cohen Marc, Gonzales Andrea, Hoppensteadt Debra, Lee Ted, Zucker Marcia L, Khalid Khaula, Laduca Frank M, Fareed Jawed
Clinical Affairs and Research & Development, ITC, Edison, NJ, USA.
J Thromb Thrombolysis. 2006 Apr;21(2):137-45. doi: 10.1007/s11239-006-4383-5.
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.
依诺肝素越来越多地用于接受经皮冠状动脉介入治疗（PCI）患者的抗凝治疗。多项报告表明，即时检验在监测接受PCI患者的依诺肝素抗凝水平方面具有实用价值。本研究的目的是评估一种新型即时检验（POCT）——HEMONOX，用于监测接受择期PCI手术患者的非枸橼酸化新鲜全血样本中依诺肝素的抗凝效果。
经机构审查委员会（IRB）批准后，从54例接受两次连续静脉注射依诺肝素的患者中采集血样；先注射0.1mg/kg，5分钟后再注射0.4mg/kg，总计0.5mg/kg。在首次推注后的基线、5分钟、10分钟、30分钟和60分钟采集血液，用于基于凝血的POCT——HEMONOX、活化凝血时间（ACT）和活化部分凝血活酶时间（aPTT）以及发色底物法抗Xa活性测定。
健康供者的基线HEMONOX凝血时间（CT）为62.6±6.2秒（n = 32），PCI患者的该值在统计学上更高（71.6±9.1秒，p = 0.0001）。在所有54例患者中，推注后10分钟总能达到的HEMONOX峰值反应>100秒，其中83%的患者CT>150秒（范围：150 - 466）。基线时未检测到抗Xa活性水平，而HEMONOX峰值CT对应治疗水平（0.85±0.14 U/ml；范围：0.61 - 1.34）。在拔除鞘管时，HEMONOX CT和抗Xa水平均显著下降。峰值反应时的HEMONOX CT提示存在3个对依诺肝素敏感性不同的患者亚组：低反应者、中反应者和高反应者。当分析来自3个关键时间点的数据时，即基线（未用药）、峰值反应（推注后10分钟）和拔除鞘管（推注后60分钟），每个患者亚组中抗Xa活性水平与HEMONOX CT的相关性≥0.85。当分析纳入所有5个时间点的数据[基线、推注后5分钟、10分钟、30分钟和60分钟]时，相关性降至≥0.83。HEMONOX检测是测量依诺肝素抗凝效果最敏感的POCT。所有患者均成功完成PCI。
HEMONOX检测可能能够在PCI期间指导依诺肝素的抗凝治疗。HEMONOX检测是在HEMOCHRON Jr. Signature + POC系统上进行的一步全血凝血检测。该方法用于评估接受0.5mg/kg静脉注射依诺肝素后接受PCI患者血样中依诺肝素的抗凝水平。结果表明，未治疗患者的基线值与达到依诺肝素治疗水平的患者之间，HEMONOX CT有明显差异。
