The prothrombin time/international normalized ratio (PT/INR) Line: derivation of local INR with commercial thromboplastins and coagulometers – two independent studies

Summary. Background: The WHO scheme for prothrombin time (PT) standardization has been limited in application, because of its difficulties in implementation, particularly the need for mandatory manual PT testing and for local provision of thromboplastin international reference preparations (IRP). Methods: The value of a new simpler procedure to derive international normalized ratio (INR), the PT/INR Line, based on only five European Concerted Action on Anticoagulation (ECAA) calibrant plasmas certified by experienced centres has been assessed in two independent exercises using a range of commercial thromboplastins and coagulometers. INRs were compared with manual certified values with thromboplastin IRP from expert centres and in the second study also with INRs from local ISI calibrations. Results: In the first study with the PT/INR Line, 8.7% deviation from certified INRs was reduced to 1.1% with human reagents, and from 7.0% to 2.6% with rabbit reagents. In the second study, deviation was reduced from 11.2% to 0.4% with human reagents by both local ISI calibration and the PT/INR Line. With rabbit reagents, 10.4% deviation was reduced to 1.1% with both procedures; 4.9% deviation was reduced to 0.5% with bovine/combined reagents with local ISI calibrations and to 2.9% with the PT/INR Line. Mean INR dispersion was reduced with all thromboplastins and automated systems using the PT/INR Line. Conclusions: The procedure using the PT/INR Line provides reliable INR derivation without the need for WHO ISI calibration across the range of locally used commercial thromboplastins and automated PT systems included in two independent international studies.     

International multicenter international sensitivity index (ISI) calibration of a new human tissue factor thromboplastin reagent derived from cultured human cells

Summary.  The international sensitivity index (ISI) of the first working standard of Simplastin HTF, a new human tissue factor thromboplastin derived from cultured human cells, has been assessed in a calibration exercise in two Canadian and five European laboratories. Calibrations against international reference preparations (IRP) were performed for the manual method and six types of automated coagulometers that cover the majority of clotting endpoint principles in routine use. The ISI was method-dependent and varied between 1.03 and 1.29 when calibrated against rTF/95 (human IRP). The ISI was also dependent on the route of calibration. Compared with calibration against rTF/95, the ISIs obtained by calibration against RBT/90 (rabbit IRP) were on average 4.4% higher ( P  < 0.005). Considering the principle of 'like vs. like', the ISIs obtained by calibration against rTF/95 should be preferred.     

Effect of lepirudin on the international normalized ratio

BACKGROUND: Many patients receiving direct thrombin inhibitor (DTI) therapy require transition to warfarin. This transition may be complicated by DTI-induced elevations in the international normalized ratio (INR). While the effect of argatroban on the INR has been characterized, data assessing the effect of lepirudin on the INR are limited. OBJECTIVE: To evaluate the effect of lepirudin on the INR. METHODS: Patients receiving lepirudin therapy between January 2000 and May 2001 were identified using the pharmacy database, and a retrospective chart review was conducted. Patients were included for analysis if they had paired activated partial thromboplastin time (aPTT) and INR data while receiving lepirudin monotherapy. RESULTS: Fifty-three paired aPTT and INR data points from 8 patients receiving lepirudin monotherapy were collected. The Organon MDA 180 instrument was used for aPTT and prothrombin time (PT) determination. Organon MDA Platelin L reagent was used for the aPTT and Organon Simplastin L reagent was used for the PT. The international sensitivity index (ISI) of the Simplastin L thromboplastin was 2.0. The mean +/- SD lepirudin dose was 0.05 +/- 0.04 mg/kg/h. Linear regression was used to identify the INRs that correspond to a therapeutic aPTT value of 45-75 seconds (1.5-2.5 times mean laboratory normal of 30 sec). The correlation between aPTT and INR was 0.77. An aPTT of 45-75 seconds with lepirudin correlated to an INR of 1.6-3.2. CONCLUSIONS: Based on laboratory results, when using a thromboplastin with an ISI of 2, lepirudin appears to elevate the INR in the absence of warfarin.     

Guidelines on preparation, certification, and use of certified plasmas for ISI calibration and INR determination.

Reliable international normalized ratio (INR) determination depends on accurate values for international sensitivity index (ISI) and mean normal prothrombin time (MNPT). Local ISI calibration can be performed to obtain reliable INR. Alternatively, the laboratory may determine INR directly from a line relating local log(prothrombin time [PT]) to log(INR). This can be done by means of lyophilized or frozen plasmas to which certified values of PT or INR have been assigned. Currently there is one procedure for local calibration with certified plasmas which is a modification of the WHO method of ISI determination. In the other procedure, named 'direct' INR determination, certified plasmas are used to calculate a line relating log(PT) to log(INR). The number of certified plasmas for each procedure depends on the method of preparation and type of plasma. Lyophilization of plasma may induce variable effects on the INR, the magnitude of which depends on the type of thromboplastin used. Consequently, the manufacturer or supplier of certified plasmas must assign the values for different (reference) thromboplastins and validate the procedure for reliable ISI calibration or 'direct' INR determination. Certification of plasmas should be performed by at least three laboratories. Multiple values should be assigned if the differences between thromboplastin systems are greater than 10%. Testing of certified plasmas for ISI calibration may be performed in quadruplicate in the same working session. It is recommended to repeat the measurements on three sessions or days to control day-to-day variation. Testing of certified plasmas for 'direct' INR determination should be performed in at least three sessions or days. Correlation lines for ISI calibration and for 'direct' INR determination should be calculated by means of orthogonal regression. Quality assessment of the INR with certified plasmas should be performed regularly and should be repeated whenever there is a change in reagent batch or in instrument. Discrepant results obtained by users of certified plasmas should be reported to manufacturers or suppliers.     

European concerted action on anticoagulation. Quality assessment of the CoaguChek Mini and TAS PT-NC point-of-care whole-blood prothrombin time monitors

BACKGROUND: International Normalized Ratios (INRs) for prothrombin time obtained with the CoaguChek Mini and TAS (RapidPointCoag) PT-NC systems are markedly different and also differ from the "true" INR. There is therefore a need for local quality assessment (QA) of the two systems. METHODS: A set of 60 lyophilized artificially depleted and 60 lyophilized coumarin plasmas were tested at 10 centers on both point-of-care testing monitors. Subsets of three and five plasmas were selected as QA plasmas and compared with the remaining 55 to assess the relative ability of the systems to characterize performance at the individual centers. The incidence of aberrant results (outliers; >15% deviation from the true INR) was also recorded. The expected incidence with the QA plasmas was calculated and compared. RESULTS: On both systems, INR with the common sets of 55 lyophilized plasmas varied considerably between centers. With the TAS PT-NC, subsets of five and three European Concerted Action on Anticoagulation (ECAA) artificially depleted plasmas gave good correlation with the 55 plasmas, but the coumarin plasmas performed less well. With the CoaguChek Mini, correlation was good with sets of five artificially depleted QA plasmas and reasonable with three but was less satisfactory with the coumarin plasmas. Outliers were detected with both types of plasmas on both test systems but with variable success. CONCLUSIONS: With the TAS PT-NC, three ECAA artificially depleted lyophilized plasmas provided reliable QA, but five lyophilized coumarin plasmas were required. With the CoaguChek Mini, five artificially depleted plasmas gave reliable QA but coumarin plasmas gave poorer results. ECAA QA plasmas provide a local system for checking INRs obtained with monitors of both types.     

International collaborative study for the calibration of proposed International Standards for thromboplastin,rabbit, plain,and for thromboplastin,recombinant, human,plain

Essentials

• Two candidate International Standards for thromboplastin (coded RBT/16 and rTF/16) are proposed.
• International Sensitivity Index (ISI) of proposed standards was assessed in a 20‐centre study.
• The mean ISI for RBT/16 was 1.21 with a between‐centre coefficient of variation of 4.6%.
• The mean ISI for rTF/16 was 1.11 with a between‐centre coefficient of variation of 5.7%.

Summary

Background

The availability of International Standards for thromboplastin is essential for the calibration of routine reagents and hence the calculation of the International Normalized Ratio (INR). Stocks of the current Fourth International Standards are running low. Candidate replacement materials have been prepared. This article describes the calibration of the proposed Fifth International Standards for thromboplastin, rabbit, plain (coded RBT/16) and for thromboplastin, recombinant, human, plain (coded rTF/16).

Methods

An international collaborative study was carried out for the assignment of International Sensitivity Indexes (ISIs) to the candidate materials, according to the World Health Organization (WHO) guidelines for thromboplastins and plasma used to control oral anticoagulant therapy with vitamin K antagonists.

Results

Results were obtained from 20 laboratories. In several cases, deviations from the ISI calibration model were observed, but the average INR deviation attributabled to the model was not greater than 10%. Only valid ISI assessments were used to calculate the mean ISI for each candidate. The mean ISI for RBT/16 was 1.21 (between‐laboratory coefficient of variation [CV]: 4.6%), and the mean ISI for rTF/16 was 1.11 (between‐laboratory CV: 5.7%).

Conclusions

The between‐laboratory variation of the ISI for candidate material RBT/16 was similar to that of the Fourth International Standard (RBT/05), and the between‐laboratory variation of the ISI for candidate material rTF/16 was slightly higher than that of the Fourth International Standard (rTF/09). The candidate materials have been accepted by WHO as the Fifth International Standards for thromboplastin, rabbit plain, and thromboplastin, recombinant, human, plain.     

A modified method of prothrombin time/International Normalised Ratio determination in capillary blood and monitoring oral anticoagulant therapy.

BACKGROUND: Oral anticoagulant therapy is monitored by a prothrombin time (PT) assay. The PT is standardised by the International Normalised Ratio (INR). The purpose of this study was to work out a modified method of PT/INR measurement in capillary blood for monitoring anticoagulation treatment. METHODS: Healthy donors, subjects with high or low haematocrit values, and oral anticoagulant-treated patients were included in the study. Plasma and capillary blood PT/INRs were determined by the standard Quick clotting assay, by the modified approach and with the CoaguChek S analyser. RESULTS: The performance characteristics of the developed method were accuracy, due to taking into account whole capillary blood haematocrit values, and precision, due to a decrease in the viscosity of the analysed samples. Implementation of the modified method showed that it is possible to use PT values of normal plasma for capillary blood INR calculation. The developed method allowed the determination of PT in capillary blood within the haematocrit value range from 0.15 up to 0.7. For capillary blood, the results of the modified method closely correlated with PT/INR values determined by the reference Quick method in venous plasma (r=0.99) and with the CoaguChek S analyser (r=0.97). CONCLUSIONS: The modified method of capillary blood PT/INR determination could be recommended for oral anticoagulant therapy monitoring.     

A comparison of INRs after local calibration of thromboplastin international sensitivity indexes.

There are approximately 300 reagent/instrument combinations for performing prothrombin times/international normalized ratios (PT/INR) in the United States. Manufacturers and laboratories continually struggle to ensure that the International Sensitivity Index (ISI) of their thromboplastin is accurate for assaying PT/INR. OBJECTIVE: This study reports the feasibility of a new method to locally calibrate ISI of thromboplastin using the mechanical STA automated coagulation analyzer (Diagnostica-Stago Inc.) and two photo-optic coagulation analyzers, the BCS (Dade-Behring) and CA-540 (Sysmex). DESIGN: Neoplastine CI+ (CI+) (Diagnostica-Stago Inc); Thromboplastin C+ (TC+); Thromborel S (TRS); and Innovin (I) (Dade-Behring) were used in this study. A mean normal PT (MNPT) was determined for each reagent/instrument combination using samples from 25 normal individuals. Manufacturer instrument specific ISI values were not available for the STA with TC+, TRS and I. The CA540 had no ISI value for CI+ and the BCS system had no manufacturer assigned ISI values for TC+ and I; generic photo-optic and mechanical ISI manufacturer values were used for these two systems. Local on-site calibration was performed using frozen plasma calibrators to determine ISI values for each thromboplastin. Post-calibration, 95 patient samples were assayed for each reagent/instrument system combination using the manufacturer ISI and the local calibrated ISI to determine the INR result. PATIENTS: Patients from whom samples were obtained included five with a lupus anticoagulant, 30 on heparin therapy, and 60 on coumadin therapy. RESULTS: Differences between manufacturer versus local calibrated ISI ranged from 0.9% to 18.9% for normal sample INRs and from 0.8% to 16.4% for patient sample INRs. The number (or proportion) of patient specimens with clinically significantly different INR values (>10.0% difference) ranged from zero for several reagent combinations to more than half (or >50.0%) of those tested for several other combinations. CONCLUSION: Our results indicated that by locally calibrating ISI values, each laboratory may eliminate variability and guesswork between different reagent/instrument systems for ISI values when performing PT/INR assays and potentially improve the clinical accuracy of their patients' PT/INR results.     

European Concerted Action on Anticoagulation (ECAA): an assessment of a method for ISI calibration of two whole blood point-of-care PT monitor systems based on lyophilized plasmas using whole blood equivalent PT

Summary.  Previously, the attempt to simplify the International Sensitivity Index (ISI) calibration of the CoaguChek Mini whole blood point-of-care test prothrombin time (PT) monitor system was successful using lyophilized plasmas from coumarin-treated patients but not with lyophilized artificially depleted plasmas. With the TAS PT-NC monitor system, both types of plasma failed to provide reliable calibrations. The present study assesses a procedure for the ISI calibration of a TAS PT-NC and CoaguChek Mini whole blood point-of-care test PT monitor systems using lyophilized plasmas. Using lyophilized artificially depleted and coumarin plasma calibrations, we have evaluated a correction for the monitor displayed PT. This was based on a 'line of equivalence' derived from the relationship between whole blood and fresh plasma PT with both types of monitor system. With the TAS PT-NC, the use of this 'line of equivalence' resulted in reliable ISI with both lyophilized coumarin and artificially depleted plasmas. There was no significant difference between mean monitor and mean reference International Normalized Ratio (INR) with the artificially depleted plasmas. With the lyophilized coumarin plasma calibrations there was only a small INR difference. Correction with the 'line of equivalence' therefore facilitates calibration of the TAS PT-NC with lyophilized plasmas. With the CoaguChek Mini, the correction based on the 'line of equivalence' did not improve results but was not required with this system.     

Accuracy and precision of the CoaguChek S versus laboratory INRs in a clinic

BACKGROUND: The CoaguChek S is the next-generation coagulation monitor for measuring the international normalized ratio (INR) that replaces the CoaguChek device. Studies are lacking comparing the CoaguChek S with local laboratory INR assessment to ensure its accuracy and precision for monitoring patients on anticoagulation. OBJECTIVE: To evaluate accuracy, precision, and technical ease-of-use of the CoaguChek S compared with laboratory measurements. METHODS: Accuracy was evaluated in 101 patients by parallel assessment of INRs (CoaguChek S and laboratory); precision was evaluated in 31 patients using duplicate INRs from CoaguChek S and laboratory and from liquid quality controls. Accuracy was determined using orthogonal regression, Bland-Altman plot, and clinical applicability (INRs discrepant in categorization of INR goal and resulting in different therapeutic decisions). Precision was examined by comparing mean difference +/- SD between repeated INRs from CoaguChek S and laboratory, coefficient of variation (CV), and coefficient of repeatability (CR). The influence of low and elevated INRs on accuracy and precision was also examined. To assess ease-of-use of the monitor, the number of technical errors was recorded. RESULTS: The CoaguChek S significantly correlated to laboratory measurement (r = 0.93); 16.7% of INRs resulted in discrepant categorization and 24.5% would have required a different therapeutic plan. The CV and CR compared well between CoaguChek S and laboratory (6% vs. 4.9%; 0.455 vs. 0.346, respectively). When subgroups of INR values <4.0 and <3.0 were evaluated, the precision improved with both methods. Precision, based on liquid quality controls, was good (CV 4.6% = low-level; 3.3% = high-level). The CoaguChek S was found to have an error rate of 1.8%. CONCLUSIONS: The CoaguChek S is an accurate and precise alternative to laboratory assessment of the INR at values <4.0; it is an efficient device with a low likelihood of errors during testing.     

Coagulometer international sensitivity index (ISI) derivation,a rapid method using the prothrombin time/international normalized ratio (PT/INR) Line: a multicenter study

Summary. Background: The original WHO procedure for prothrombin time (PT) standardization has been almost entirely abandoned because of the universal use of PT coagulometers. These often give different international normalized ratio (INR) results from the manual method, between individual makes of instruments and with instruments from the same manufacture. Method A simple procedure is required to derive local INR with coagulometers. The PT/INR Line method has recently been developed using five European Concerted Action on Anticoagulation (ECAA) certified plasmas to derive local INR. This procedure has been modified to derive a coagulometer PT/INR Line providing International Sensitivity Index (ISI) and mean normal PT (MNPT) for coagulometers and give local INR. Results have been compared with conventional ISI calibrations at the same laboratories. Results: With human thromboplastins, mean ISI by local calibration was 0.93 (range: 0.77–1.16). With the PT/INR Line, mean coagulometer ISI was higher, for example 0.99 (0.84–1.23) but using the PT/INR Line derived MNPT there was no difference in local INR. Between‐centre INR variation of a certified validation plasma was reduced with human and bovine reagents after correction with local ISI calibrations and the PT/INR Line. Conclusion: The PT/INR Line–ISI with its derived MNPT is shown to provide reliable local INR with the 13 different reagent/coagulometer combinations at the 28 centres in this international study.     

凝血酶原时间ISI/INR系统测定中的一些问题及改进意见

目的对凝血酶原时间(PT)测定ISI/INR系统出现的一些问题提出相应的改进建议。方法对上海市12家医院在用的仪器和匹配的PT试剂,对日常使用的正常血浆平均凝血酶原时间(MNPT)作调研实测,将结果进行分析;调查试剂的仪器特定(spec ific)国际敏感度指数(ISI)值与世界卫生组织(WHO)的手工法ISI定标值之间的差异;用2种已知国际标准化比值(INR)的异常参比血浆代替WHO的ISI系统作质控并行比较。结果12家中有4家日常使用的平均正常凝血酶原时间(MNPT)明显偏离实测值,分别为0.8、0.9、1.0和1.8 s。用WHO CRM149R参比,用手工法标定的凝血活酶和109 mmol枸橼酸钠抗凝的不同PT值血标本,在Sysm ex1500型、C.2000型仪器上测定试剂的仪器特定ISI,其结果比手工法分别减少4.1%和4.7%,但采用HEPES-枸橼酸钠抗凝剂标本时,2种型号仪器的特定ISI比手工法分别减少16.7%及7.7%。用已知INR异常参比血浆,国产品与进口品对照的结果良好。结论受调研12家中,有4家血凝分析仪器调研时实测的MNPT明显偏离日常使用值。有几家医院试剂的仪器特定ISI值也存在问题,建议纠正。用已知INR异常参比血浆代替WHO手工法标定凝血活酶ISI法作质控,使用简便,又不需MNPT参数,值得推广。     

Accuracy of the avosure PT pro system compared with a hospital laboratory standard

OBJECTIVE: To compare international normalized ratio (INR) values obtained using the AvoSure PT Pro point-of-care (POC) system with those obtained using a standard laboratory method. METHODS: Forty-one INR values obtained from the POC system were compared with those obtained from a standard laboratory method. The POC method was evaluated for both laboratory and clinical agreement. To evaluate laboratory agreement, various analyses were used, including mean-squared prediction error (MSE) and mean prediction error (ME), Bland-Altman analysis, correlation, and paired t-test comparing group INR means. For clinical accuracy, discrepant pairs were identified and evaluated to determine whether dosage adjustments would have been needed based on values obtained. RESULTS: The POC system demonstrated modest precision (MSE = 0.147, 95% CI 0.065 to 0.228) and relatively little bias (ME = 0.090, 95% CI -0.025 to 0.205). Bland-Altman analysis also suggested good agreement at average INRs from 2.0 to 3.0. At average INR values >3.0, the POC system consistently overestimated INR. Values obtained with the POC system were significantly correlated with those obtained from the hospital laboratory (r = 0.77; p < 0.001). Similarly, mean +/- SD POC INR did not differ significantly from the laboratory-determined INR (2.45+/-0.59 vs. 2.37+/-0.48, respectively; p = 0.176). Regarding clinical accuracy, the values clinically agreed in 85.4% of the cases. CONCLUSIONS: The AvoSure PT Pro POC system appears to be useful for INR values within the 2.0-3.0 range, but values outside of this range should probably be confirmed with a standard laboratory method.     

Comparison of local International Sensitivity Index calibration and ''Direct INR'' methods in correction of locally reported International Normalized Ratios: an international study

BACKGROUND: It is no longer feasible to check local International Normalized Ratios (INR) by the World Health Organization International Sensitivity Index (ISI) calibrations because the necessary manual prothrombin time technique required has generally been discarded. OBJECTIVES: An international collaborative study at 77 centers has compared local INR correction using the two alternative methods recommended in the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis guidelines: local ISI calibration and 'Direct INR'. METHODS: Success of INR correction by local ISI calibration and with Direct INR was assessed with a set of 27 certified lyophilized plasmas (20 from patients on warfarin and seven from normals). RESULTS: At 49 centers using human thromboplastins, 3.0% initial average local INR deviation from certified INR was reduced by local ISI calibration to 0.7%, and at 25 centers using rabbit reagents, from 15.9% to 7.5%. With a minority of commercial thromboplastins, mainly 'combined' rabbit reagents, INR correction was not achieved by local ISI calibration. However, when rabbit combined reagents were excluded the overall mean INR deviation after correction was reduced further to 3.9%. In contrast, with Direct INR, mean deviation using human thromboplastins increased from 3.0% to 6.6%, but there was some reduction with rabbit reagents from 15.9% to 10% (12.3% with combined reagents excluded). CONCLUSIONS: Local ISI calibration gave INR correction for the majority of PT systems but failed at the small number using combined rabbit reagents suggesting a need for a combined reference thromboplastin. Direct INR correction was disappointing but better than local ISI calibration with combined rabbit reagents. Interlaboratory variability was improved by both procedures with human reagents only.     

Importance of device evaluation for point-of-care prothrombin time international normalized ratio testing programs

OBJECTIVE: To determine the accuracy of 2 commercially available point-of-care devices relative to plasma international normalized ratio (INR) values. PATIENTS AND METHODS: Point-of-care INR testing was performed with the CoaguChek and ProTime 3 devices in consecutive patients attending an anticoagulation clinic between June 18, 2003, and August 6, 2003. Results were compared with plasma INRs using a sensitive thromboplastin (International Sensitivity Index, 1.0). RESULTS: Ninety-four patients agreed to participate in the study. Relative to the plasma INR, values were in agreement +/-0.4 INR unit 82% and 39% of the time for the CoaguChek and ProTime 3 devices, respectively. The mean +/- SD CoaguChek INRs were 0.2+/-0.31 unit lower, whereas ProTime 3 INRs were 0.8+/-0.68 unit higher than plasma INR values. Treatment decisions based on these data would have resulted in inappropriate dose adjustments 10% and 22% of the time for these 2 respective devices. Correlation with plasma was greater for the CoaguChek (r2=0.90) compared with the ProTime 3 device (r2=0.73). CONCLUSIONS: Optimal warfarin treatment requires accurate measurement of the INR. The choice of a point-of-care device for INR management depends on the reliability of INR data generated by the device.     

Accuracy, clinical correlation, and patient acceptance of two handheld prothrombin time monitoring devices in the ambulatory setting.

OBJECTIVE: To evaluate the accuracy, clinical correlation, ease of use, and patient acceptance of the Coaguchek and the ProTime Microcoagulation System as compared with standard laboratory methods for prothrombin time determination. METHODS: A total of 30 prothrombin times, expressed as international normalized ratios (INRs), were determined by each handheld device for comparison with standard laboratory testing. Accuracy was evaluated by calculating the absolute difference for each pair of INR values. Clinical correlation was defined as an INR obtained by the handheld monitor that would have resulted in the same therapeutic decision as the INR obtained by the standard laboratory method. Subjects were surveyed to determine which method of INR determination they preferred and their reasons for that preference. RESULTS: Accuracy was superior with the Coaguchek monitor. The absolute difference (mean +/- SD) in the laboratory and Coaguchek INRs was 0.28+/-0.23 (p = 0.96). The absolute difference (mean +/- SD) in the laboratory and the ProTime Microcoagulation System INRs was 0.56+/-0.34 (p < 0.001). For clinical correlation, two out of 24 (8.3%) INRs with the Coaguchek were sufficiently different from the laboratory INR to have resulted in a different therapeutic decision, compared with 12 out of 24 (50%) with the ProTime Microcoagulation System (p < 0.005). Of subjects surveyed, 77.8% preferred the finger stick method. CONCLUSIONS: The Coaguchek was superior to the ProTime Microcoagulation System in accuracy, clinical correlation, and ease of use. The study also showed that patients preferred capillary blood sampling by finger puncture over venipuncture for INR monitoring.     

广东省凝血酶原时间测定的室间质量评价

目的 探讨广东省临床实验室监测凝血酶原时间（PT）的检测状况及影响PT测定室间可比性的因素.方法 通过每年两次定期向全省参评实验室寄发质控样品（每次5个样品）,然后对其回报的数据进行统计分析,作出实验室检验水平的评价.结果 近年来全省实验室间PT（INR）测定结果的CV值尽管有逐渐下降的趋势,但室间变异仍然相当高.同一凝血活酶试剂的测定结果,PT（INR）的CV明显大于PT（sec）的CV,特别是对异常水平质评物的测定.结论 凝血活酶试剂敏感度指数（ISI）值标定的不准确性和INR计算不正确的是引起广东省临床实验室间凝血酶原时间测定变异大的主要原因.     

Optimizing warfarin reversal – an ex vivo study

Summary.  Background: Warfarin reversal is a common clinical situation. This is commonly performed using vitamin K and, depending on the urgency, fresh frozen plasma (FFP), prothrombin complex concentrates (PCCs), or activated factor VII. Even though PCCs are widely used, the ideal dosing regimen is far from established. Objectives: To verify differences in warfarin reversal patterns using FFP, recombinant FVIIa (rFVIIa), and PCC; and to test the hypothesis that supratherapeutic International Normalized Ratios (INRs) might not correlate with thrombin generation (TG) and identify the ideal concentrations of PCC required to reverse various INR thresholds. Methods: We studied the effects of FFP, rFVIIa and Beriplex  P/N on the INR and TG, using the calibrated automated thrombography assay in ex vivo warfarinized plasma. Plasmas with different INRs were spiked with different concentrations of Beriplex  P/N. Results: Beriplex  P/N was the only agent that completely normalized TG and the INR. The endogenous thrombin potential (ETP) and the peak thrombin showed a significant negative correlation with all INRs. The ETP and velocity of TG reached a plateau at an INR of ∼ 4.0. A concentration equivalent to a dose of 30 IU kg⁻¹ Beriplex  P/N normalized the ETP, the INR, FII, FVII, FIX and FX of samples with INRs  ≥ 4.0. Higher doses resulted in hypercoagulable TG patterns. A concentration equivalent to a dose of 20 IU kg⁻¹ was sufficient to reverse warfarin at an INR range of 2.0–3.9, as judged by the same tests. Conclusions: Warfarin reversal algorithms could be simplified with the adoption of this strategy utilizing two doses of PCC, depending on the INR of the patient. This would also lead to cost reductions and, possibly, a reduction in thrombotic risk.     

Comparison of quick and owren prothrombin time with regard to the harmonisation of the International Normalised Ratio (INR) system.

Prothrombin time (PT) is tested mostly to monitor patients on oral anticoagulant treatment. The International Normalised Ratio (INR) was introduced to improve and harmonise PT results and therapeutic range globally for patient care and the scientific literature. We studied the Quick PT in 179 patients and the Owren PT in 137 patients on oral anticoagulant therapy using two different reagents for the two methods of measuring PT. We assessed the clinical significance of the INR results obtained by each method using the two reagents and compared the Quick and Owren methods. We conclude that with the Quick method individual INR results differed from each other too much clinically, while using the Owren method individual INR results were clinically acceptable. Our opinion is that we should develop the INR system using the Owren PT method rather than the Quick to improve patient care.