Monitoring Of Oral Anticoagulant Therapy Research Articles

Comparison and evaluation of a Point-of-care device (CoaguChek XS) to Owren-type prothrombin time assay for monitoring of oral anticoagulant therapy with warfarin

Background The standardized test used for evaluating the effect of warfarin is the prothrombin time (PT) which is measured and expressed in international normalized ratio (INR). Regular control of treatment intensity is required since inappropriate dosage increases the risk for complications. Portable point-of-care analytical instruments for measurement of capillary whole blood PT have been available for the last decades. The purpose of this study was to compare and evaluate INR values obtained by the point-of-care device CoaguChek XS, to Owren PT in a hospital setting. Materials and Methods In 397 warfarin-treated patients, capillary whole blood was analyzed with the CoaguChek XS and the results were compared to analysis of venous plasma samples with the Owren PT assay. To study reproducibility and rule out preanalytical errors, a subgroup of 152 patients had two capillary blood samples analyzed with the CoaguChek XS. Results In 397 patients, with a median age(±2SD) of 69.0(50-88) years, there was a positive correlation between results from the CoaguChek XS and the Owren-type PT assay (r = 0.94;p < 0.001) and concordance of 88.2%. The mean INR difference (S.D) was 0.02 (0.22). Comparison of the 152 double samples analyzed with the CoaguChek XS, produced a positive correlation of 0.99; p < 0.001. Conclusions The CoaguChek XS presents reproducible, highly comparable results with Owren PT at therapeutic levels of INR. The CoaguChek XS seems to produce better results than the earlier CoaguChek S, probably due to a new method of PT measurement where levels of fibrinogen and haematocrit do not affect the outcome.

Intrahospital Correlation of the International Normalized Ratio

Background. Monitoring of oral anticoagulant therapy (OAT) is usually accomplished by measuring prothrombin time and the international normalized ratio (INR). However, thromboplastins have different responsiveness and sensitivity to vitamin K-dependent coagulation factors depletion. Several studies have shown INR variation when low sensitive thromboplastins are used. This study compared INR variability between two laboratories using highly sensitive thromboplastins. Methods. A total of 237 plasmas were tested, half of them from patients under OAT. Samples were tested simultaneously in two laboratories: in laboratory A, a Behring Coagulation Timer instrument and a human recombinant thromboplastin (Innovin, Dade Behring) (ISI 1.01) were used. In laboratory B, a Thrombolyzer Compact (Behnk Elektronik) and a rabbit brain thromboplastin (Simplastin Excel S, Organon Teknika) with an ISI of 1.30 were used. Statistical analysis was carried out according to the method of Bland and Altman. Results. Even though high correlation coefficients were obtained when comparing both laboratories, Bland-Altman analysis showed a variation of INR between laboratories ranging from -0.77 to +1.07. After logarithmic transformation of data, these values yielded a variation of the INR either 25% below or 44% above. Conclusions. These results are clearly inadequate for clinical use because such a variation would most probably induce the clinician to make a change in warfarin dose. Standardization of instruments, reagents, and controls is warranted to decrease this variation.

Performance Evaluation of a New Small-Volume Coagulation Monitor

The SmartCheck INR (Unipath, Bedford, England) is a point-of-care device for professional and patient self-monitoring of oral anticoagulant therapy. It measures the international normalized ratio (INR) and assesses test strip integrity, temperature, and sample quality. No significant differences were found in SmartCheck INR results from 3 different instruments or in 3 test-strip lots. Within run imprecision was 0.89% and 6.36% for low and high control samples, respectively (mean INR, 0.99 and 4.08, respectively). Comparability was assessed in 68 patients receiving warfarin by using PTHS Plus (Instrumentation Laboratory, Lexington, MA) and Innovin (Dade Behring, Marburg, Germany) thromboplastins. Good correlations were observed between the methods (r = 0.89 and r = 0.90, respectively) with no significant differences in means: SmartCheck INR, 2.82; Innovin, 2.75; PTHS Plus, 2.74. Clinical agreement with laboratory methods was 88% for Innovin and 97% for PTHS Plus. The SmartCheck INR was easy to use with no mechanical failures during the evaluation and a low test-strip failure rate of 4.7%. The SmartCheck INR provides accurate and reproducible results and is suitable for routine monitoring of oral anticoagulant therapy in the majority of patients.

Developing Educational Materials to Facilitate Adherence: Pediatric Thrombosis as a Case Illustration

Developing Educational Materials to Facilitate Adherence: Pediatric Thrombosis as a Case Illustration

Oral anticoagulant therapy and telemedicine

We read the interesting paper by Testa et al.1 and the editorial comment by Pengo2 about the devolution of oral anticoagulant therapy (OAT) by using a telemedicine system that involves rest houses, peripheral hospitals and general practitioners. The architecture of the system, which improves quality of therapy and patient satisfaction, as those preliminary findings report, seems to be a valid future alternative in the monitoring of OAT. A few months ago, the Anticoagulation Clinic (AC) of Cagliari (Italy), which operates in the frame of the Italian Federation of Anticoagulation Clinics (FCSA), has started a similar project, by involving about 150 patients in selftesting and a control group matched for sex, age and diagnosis, followed by the AC and monitored by TAONET (EDP-Progetti, Bolzano, Italy). Patients were all on chronic OAT and criteria for enrollment in the study were the following: patients on OAT since at least 3 months; patients who cannot leave home because of serious physical illness, advanced age; patients who live far from the AC, lack of time due to hard work. The main outcomes of the study were the following: a) overdosage states, b) thrombotic and haemorrhagic events, c) time spent in the therapeutic range, and d) quality of life assessed by means of a questionnaire. After a training course, every patient received a portable coagulometer3 (Coagucheck S, Roche Diagnostics, Basel, Switzerland), which was submitted to a 3-monthly quality control by comparing the prothrombin time-INR measurement with that of the AC. We also asked the software house to create a personal and safe account to connect the patient to the referring AC through a web site. This procedure allows patients to interact with the AC where we use a system (TAONET), firstly designed by MM in 1999, to devolve OAT monitoring on territorial settings. We report here a brief description of the system: TAONET allows patient management in the territorial settings coordinated and assisted by the referring AC, the application to the involved territorial seats of the same quality standards as those of the AC, the extension of the procedure to all the remaining territory, with differentiated supports, according to the dedicated caregiver or to the patient himself. The system is developed on an Oracle standard procedure and is organised as a centralised netsupported program. The hardware is composed of a modular system, using a server and PC stations in the AC and workstations in the peripheral districts, and utilised by family doctors, nurses, pharmacies, and rest houses. Patients in self-testing can rely on a bidirectional connection with the AC; they can send their clinical data (e.g. pharmacological variations, intervening diseases, complications, etc.) and the INR value (obtained by portable monitor) by compiling a pre-set electronic datasheet and by receiving the schedule with the adjusted dose regimen at home in no more than 10 min. The questionnaire is relevant to dose assumption, pharmacological variations, possible haemorrhagic events, surgery, diet behaviour, and gives the patients the possibility of sending to doctors at the AC personal comments about the reported events. Every modification in therapy or in the clinical status will be simultaneously registered by the central data-base and will remain under control of the dedicated staff of the AC. The system allows a manual dose adjustment or an electronic proposal by the dose calculation algorithm of the program. Monitoring patients in self-testing could lead to an improvement in quality of life of the single patient even greater than that of patients monitored by the family doctors or by the nursing centres since it can be considered an “at home OAT monitoring”, under the direct control of the AC. Moreover, these patients have the possibility of interacting with the AC via this system, even when they are outside home or abroad, by simply finding an Internet point and using their personal connection to the web site. In conclusion, we think that in the near future this system could significantly improve the management of patients treated with coumarins. Even if this system will not be immediately available to all patients, a considerable proportion will save time and money, by simultaneously reducing the huge overcrowding in the AC. Coumarins could therefore be more resistant to the entry of new anticoagulants and to be still the drugs of choice in particular settings. Finally, a system like the TAONET could be helpful in the clinical monitoring of patients treated with new anticoagulants, which do not need a laboratory control as recently suggested4. A progressive lack in time of adherence to therapy may occur. Patients could periodically interact with the AC by answering a simple questionnaire on drug assumption, their general

Phospholipid composition controls thromboplastin sensitivity to individual clotting factors.

Tissue factor is the active ingredient in thromboplastin reagents used to perform prothrombin time (PT) clotting tests to monitor oral anticoagulant therapy and to screen for clotting factor deficiencies. Thromboplastins are complex mixtures prepared from extracts of brain or placenta, although newer thromboplastins contain recombinant tissue factor incorporated into phospholipid vesicles. Thromboplastins can vary widely in their sensitivity to reductions in the levels of vitamin K-dependent clotting factors. A system to compensate for this, the International Sensitivity Index (ISI) and International Normalized Ratio (INR), has revolutionized the monitoring of oral anticoagulant therapy. The INR system is also sometimes used to monitor coagulopathies in patients with sepsis or liver failure, applications for which it was not originally designed and for which it has not been rigorously validated. To better understand thromboplastin performance, we systematically investigated which properties of recombinant thromboplastins influence their sensitivities to changes in the levels of specific clotting factors. We now report that relative sensitivities to changes in the plasma levels of factors V, VII, X (FV, FVII, FX) and prothrombin are differentially influenced by a recombinant thromboplastin's content of phospholipid and sodium chloride. Furthermore, thromboplastins of similar ISI values may exhibit quite different sensitivities to each of these clotting factors. Differing sensitivities of thromboplastin reagents to individual clotting factor levels have implications for monitoring of oral anticoagulant therapy and interpreting results of the PT assay.

Preanalytical Variables and Off-Site Blood Collection: Influences on the Results of the Prothrombin Time/International Normalized Ratio Test and Implications for Monitoring of Oral Anticoagulant Therapy

Preanalytical Variables and Off-Site Blood Collection: Influences on the Results of the Prothrombin Time/International Normalized Ratio Test and Implications for Monitoring of Oral Anticoagulant Therapy

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

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. 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. 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). The modified method of capillary blood PT/INR determination could be recommended for oral anticoagulant therapy monitoring.

Home INR monitoring of oral anticoagulant therapy in children using the CoaguChek™ S point-of-care monitor and a robust education program

Introduction Management strategies such as self-monitoring of anticoagulant therapy have been reported with increased frequency. Whilst patient education is frequently mentioned, details regarding the educational interventions employed are scarce. This study aimed to improve the outcomes of home monitoring of warfarin therapy in children through the development and implementation of a robust intervention, based upon the PRECEDE model of education. Materials and methods Participating parents had to complete an intensive education and training program. After demonstrating practical and theoretical competency, parents commenced home monitoring. Every second scheduled home INR (H-INR) required a paired INR on the same day, obtained by a trained pathology collector (C-INR). Demographic and statistical outcome data was collected. Results Parental understanding of warfarin therapy improved significantly following the educational intervention ( p < 0.0001). 65.5% of H-INRs and 64.4% of C-INRs were within the target range (ns). Lin's correlation coefficient between H-INRs and C-INRs was 0.949. There were no warfarin-related adverse events. Conclusion This study demonstrated a significant improvement in parental knowledge following participation in a robust educational intervention. Furthermore, compared to previous reports in children, a greater level of correlation between home and hospital-based INRs was achieved by participating parents. The use of similar educational interventions may serve to improve the outcomes of similar management strategies.

Preanalytical Variables and Off-Site Blood Collection: Influences on the Results of the Prothrombin Time/International Normalized Ratio Test and Implications for Monitoring of Oral Anticoagulant Therapy

The quality of oral anticoagulant therapy management with coumarin derivatives requires reliable results for the prothrombin time/International Normalized Ratio (PT/INR). We assessed the effect on PT/INR of preanalytical variables, including ones related to off-site blood collection and transportation to a laboratory. Four laboratories with different combinations of blood collection systems, thromboplastin reagents, and coagulation meters participated. The simulated preanalytical variables included time between blood collection and PT/INR determinations on samples stored at room temperature, at 4-6 degrees C, and at 37 degrees C; mechanical agitation at room temperature, at 4-6 degrees C, and at 37 degrees C; time between centrifugation and PT/INR determination; and times and temperatures of centrifugation. For variables that affected results, the effect of the variable was classified as moderate when <25% of samples showed a change >10% or as large if >25% of samples showed such a change. During the first 6 h after blood collection, INR changed by >10% in <25% of samples (moderate effect) when blood samples were stored at room temperature, 4-6 degrees C, or 37 degrees C with or without mechanical agitation and independent of the time of centrifugation after blood collection. With one combination of materials and preanalytical conditions, a 24-h delay at room temperature or 4-6 degrees C had a large effect, i.e., changes >10% in >25% of samples. In all laboratories, a 24-h delay at 37 degrees C or with mechanical agitation had a large effect. We observed no clinically or statistically relevant INR differences among studied centrifugation conditions (centrifugation temperature, 20 degrees C or no temperature control; centrifugation time, 5 or 10 min). We recommend a maximum of 6 h between blood collection and PT/INR determination. The impact of a 24-h delay should be investigated for each combination of materials and conditions.

Low frequency of elevated prothrombin times in patients with lupus anticoagulants when using a recombinant thromboplastin reagent: implications for dosing and monitoring of oral anticoagulant therapy

Many patients with lupus anticoagulants (LA) are treated with oral anticoagulation and monitored using the international normalised ratio (INR) derived from the prothrombin time (PT). Recent reports have produced conflicting conclusions about the extent to which LA interferes with PT determination. The degree of anticoagulation may be overestimated in a patient whose LA affects the PT. A number of reports conclude that specific thromboplastin reagents containing recombinant tissue factor are sensitive to the presence of LAs and should not be used to monitor oral anticoagulant therapy in these patients. These studies were performed on orally anticoagulated patients. The present retrospective study on 400 patients with LAs who were not receiving therapeutic anticoagulation was performed to ascertain the frequency of prolonged PT in these patients when using Innovin recombinant thromboplastin. Only 17 (4.3%) out of 400 had prolonged PT in the presence of LA. As this is a low prevalence, and not all patients with LAs will require anticoagulant therapy, it is concluded that baseline INR determination should be used to highlight the need to monitor individual patients with LA-insensitive reagents. As the use of moderate-intensity oral anticoagulation for patients with LAs and previous thrombosis is receiving wider acceptance, an informed approach to anticoagulant monitoring will reduce the possibility of underanticoagulating patients receiving this therapy.

Long-term stability and reproducibility of Coagu Chek test strips

Whole-blood point-of-care testing prothrombin time monitors are being used on an increasing scale for the monitoring of oral anticoagulant therapy. These monitors are used with disposable test strips containing tissue factor reagent. The purpose of the present study was to assess the stability of different CoaguChek-S strip lots for a period of one year. Ten strip lots introduced successively in the Netherlands were obtained from the manufacturer's representative and stored at 4-8 degrees C. Six deep-frozen pooled plasmas were analyzed for the prothrombin time and INR with the strips at six or seven occasions spread over one year. The test plasmas were recalcified immediately before application to the CoaguChek-S system. Regression analysis was performed on the clotting times obtained with each plasma. In the majority of cases (i.e.95%), no significant change was observed at the 5% significance level. A significant change was observed in only 3 cases. In addition, a ranking statistic was used as test of a monotonic relationship in the two-way analysis of variance. The results of the ranking statistic were not significant for any strip lot, indicating that the test strips were stable under these storage conditions. The reproducibility of INR measured with the CoaguChek-S was assessed. The mean within-run coefficient of variation (CV) of INR ranged from 2.58% to 3.36% (CV). The between-lot variation of the mean INR ranged from 3.2 to 4.5 % (CV). The over-all variation of single INR measurements, i.e. including between-lot and within-lot, ranged from 5.0 to 6.0 % (CV).

Reply to rebuttal: A problem of calibration in the paper ‘Point of care monitoring of oral anticoagulant therapy in children’

Replytorebuttal:Aproblem of calibrationinthe paper ‘Pointofcaremonitoringof oral anticoagulanttherapy in children ’ -

Rebuttal: A problem of calibration in the paper ‘Point of care monitoring of oral anticoagulant therapy in children’

Rebuttal:A problem of calibrationin thepaper ‘Point of care monitoring of oral anticoagulant therapyin children ’ -

Unreliability of Point of Care Devices for INR Monitoring of Oral Anticoagulant Therapy. A Re-Evaluation.

Oral anticoagulant treatment with vitamin K antagonists has been encumbered by the need for interval monitoring of INRs to adjust dosage. Point of Care (POC) testing of capillary blood has come into widespread use because of the advantages of rapid analysis and dose adjustment. To assess the reliability of this procedure, we compared INR results from 2 POC devices from different manufacturers - POC1 and POC2 - and compared these results to standard assays on venous samples with a BCS automated analyzer.78 patients on warfarin for at least 3 months were studied. Results of 56 patients with POC2 and 76 patients with POC1 were compared to the BCS. Capillary blood samples were taken within 30 minutes of the venous draw. The therapeutic INR range was considered to be 2.0–3.5.The bias plots for the 2 POC methods compared to the reference INR are shown in the 2 Figs, below. Within the therapeutic range, 71% and 85% of the results correlated with BCS for POC1 and the POC2, respectively. Both instruments showed the greatest variation from the reference measurement at INR values greater than 2.5 Both POC methods demonstrated clinically relevant overestimates of INR(see table). [Display omitted] [Display omitted] Agreement % of Reference INR Values to POC INRReference INR*POC1-subtherapeuticPOC1-therapeuticPOC1-supratherapeuticPOC2-subtherapeuticPOC2-therapeuticBCS-subtherapeutic77%23%-63%37%BCS-therapeutic4%71%25%5%85%BCS-supratherapeutic--100%-33%* INR = 2.0–3.5Conclusion: This study raises a significant question rearding the accuracy of POC methods for INR determinations. Despite ease of use and immediacy of results, the lack of correlation, even under study conditions, and the potentials for under-and overdosing makes relying on these devices problematic.

Properties of recombinant human thromboplastin that determine the International Sensitivity Index (ISI)

Prothrombin Time (PT) clotting tests are widely used to monitor oral anticoagulation therapy and to screen for clotting factor deficiencies. The active ingredient in PT reagents (thromboplastins) is tissue factor, the integral membrane protein that triggers the clotting cascade through the extrinsic pathway. Several years ago, a system for calibrating and using thromboplastin reagents, known as the International Sensitivity Index (ISI) and the International Normalized Ratio (INR), was developed to standardize monitoring of oral anticoagulant therapy. The ISI/INR method, while revolutionizing the monitoring of coumarin therapy, has been criticized for a number of perceived shortcomings. We have undertaken a series of studies aimed at achieving a detailed understanding of which parameters influence the ISI values of thromboplastin reagents, with an ultimate goal of creating 'designer thromboplastins' whose sensitivities to the various clotting factors can be individually tailored. In this study, we demonstrate that ISI values of thromboplastin reagents based on relipidated, recombinant human tissue factor can be controlled by a combination of changes in the phospholipid content (in particular, the levels of phosphatidylserine and phosphatidylethanolamine) and ionic strength. The sensitivity of a given thromboplastin reagent can be increased (i.e. its ISI value decreased) by decreasing the content of phosphatidylserine and/or increasing the ionic strength. The molar ratio of phospholipid to tissue factor, on the other hand, had essentially no impact on ISI value.

Patient self-monitoring of oral anticoagulant therapy: potential benefits and implications for clinical practice.

Coumarin derivatives are widely used oral anticoagulants for patients with chronic atrial fibrillation, venous thromboembolism, valvular heart disease, myocardial infarction or a mechanical prosthetic heart valve. Because of the narrow therapeutic window associated with coumarins and the potential for drug interactions, frequent monitoring of anticoagulation is required to maintain the International Normalized Ratio (INR) between 2.0 to 3.5 for most clinical indications. Monitoring of oral anticoagulant therapy is placing a considerable burden on healthcare providers because many patients require life-long treatment with coumarins, and because of an increasing number of elderly patients with conditions that are treated with coumarins. A novel approach that might, in part, address this healthcare need is patient self-monitoring of anticoagulation with a portable coagulometer. Several cohort studies and randomized controlled trials have found that anticoagulation self-monitoring is as good as, or better than, conventional monitoring in a specialized anticoagulation clinic or by a general practitioner. The advantages of anticoagulation self-monitoring include reduced patient inconvenience relating to anticoagulation clinic visits and laboratory monitoring of warfarin therapy, and fewer INR levels outside the therapeutic INR range if INR measurements are preformed more frequently with anticoagulation self-monitoring. Thus, anticoagulation self-monitoring has the potential to reduce the incidence of thromboembolic and bleeding episodes in patients who are receiving long term oral anticoagulant therapy. The potential drawbacks of anticoagulation self-monitoring include the costs of the portable coagulometer. Additionally, self-monitoring is limited to patients who have the cognitive and physical capabilities to perform the technique required for the portable coagulometer.

The International Normalized Ratio during Concurrent Warfarin and Argatroban Anticoagulation: Differential Contributions of Each Agent and Effects of the Choice of Thromboplastin Used

Oral anticoagulants such as warfarin induce depletion of vitamin K-dependent coagulation factors, causing prolongation of the prothrombin time (PT) and the PT-International Normalized Ratio (INR). The available thromboplastins used for measuring the PT vary in their sensitivity to coagulation factor depletion, and each is assigned an International Sensitivity Index (ISI) that is used when calculating the INR. Traditional monitoring of oral anticoagulant therapy using the INR is confounded during concurrent therapy with direct thrombin inhibitors, such as argatroban, that also prolong the INR (1)(2)(3). Although alternative monitoring methods have been suggested for use in this setting (2)(3), guidelines allowing for refined interpretation of the INR would also be useful. To facilitate the development of such guidelines, we have characterized in vitro the differential effects of warfarin and argatroban, as well as the choice of thromboplastin used, on the INR during anticoagulation with both agents. For this study, plasma specimens were obtained from 10 healthy donors (laboratory personnel) and 35 patients on warfarin therapy, in accordance with policies of the institution’s responsible committee. Blood was collected into evacuated tubes (38 g/L sodium citrate), and plasma was prepared by the centrifugation of the blood within 30 min of collection. The only selection criterion for the patient group was that each was on warfarin therapy, and both inpatients and outpatients were included. In addition, four plasma pools (each prepared from at least 10 individuals) were obtained from Harris Laboratories. One plasma pool was from healthy donors, and three pools were from patients on warfarin therapy exhibiting generally similar levels of oral anticoagulation. Plasma specimens were stored at −30 °C for up to 2 weeks and thawed rapidly immediately before testing. The PT of each individual or pooled plasma specimen was determined in the absence and presence of …

Monitoring of oral anticoagulant therapy in lupus anticoagulant positive patients with the anti-phospholipid syndrome.

Introduction of the International Normalized Ratio (INR) has improved the standardization of laboratory control of oral anticoagulant therapy (OAT). However, it has been reported that misleading INR results can be obtained from OAT patients with lupus anticoagulant (LA). To investigate this claim, we studied 35 OAT patients, 14 of whom had anti-phospholipid syndrome (APS) with a documented LA. Attainment of anticoagulation was confirmed by chromogenic assay of factor VII and factor X. Prothrombin times were performed using eight thromboplastins (five derived from rabbit brain, two recombinant human tissue factor and one made from human placenta) with an International Sensitivity Index (ISI) of <1.40. When using the thromboplastin manufacturers' ISI there was a significant difference (ANOVA, P<0.0001) between INR results obtained with the eight reagents for both APS (average CV = 12.4%) and non-APS (average CV = 12.5%) patient groups. Variation using the eight thromboplastins was assessed by calculating the CV for each sample; these values were then pooled for each patient group to give the average CV for all samples with all reagents for the two patient groups. Results for both patient groups exhibited markedly reduced variation (APS group average CV = 6.5%, non-APS group average CV = 5.8%) when locally assigned ISI values were employed in the calculation of INRs. Our data does not support the suggestion that the INR may not reflect the true level of anticoagulation in the long-term warfarin-treated patient, in whom lupus anticoagulant was detected. However, there was strong evidence that thromboplastin use should be restricted to those clot detection systems for which the reagent's manufacturer has assigned an ISI, or local ISI assignment must be undertaken. The inappropriate use of a generic (i.e. optical or mechanical clot detection system without regard to specific analyser type) ISI value can lead to ambiguous results.

Plasma levels of factors II, VII and X and their relationship to the international normalized ratio during chronic warfarin therapy.

Monitoring of oral anticoagulant therapy is usually undertaken with the prothrombin time (PT), which is influenced by factors II, X, and VII. A number of studies have suggested that the prothrombin (factor II) level may be the most important determinant of the therapeutic efficacy of these drugs. Although some studies suggest that oral anticoagulants induce a similar residual level of plasma vitamin K-dependent proteins, others have called this into question. We therefore measured plasma levels of factors II, X, and VII in 50 patients undergoing chronic Warfarin therapy. The plasma levels of factors II, X, and VII were significantly different. Although the factor X levels of all plasmas were < 30%, levels of factors II and VII were > 30% in 14% and 50% of the samples, respectively. Multivariable analysis showed factor II levels to be the least significant of the three factors measured in determining the international normalized ratio of plasma or whole blood. Thus, plasma levels of the vitamin K-dependent coagulation factors are not equal in patients on chronic Warfarin therapy. If factor II (prothrombin) levels are indeed the major determinants of the therapeutic efficacy of Warfarin, alternative means of monitoring that more accurately reflects prothrombin levels should be evaluated.