-
A M H P van den Besselaar
Journal of Thrombosis and Haemostasis 12/2011; 10(2):303-5. · 5.73 Impact Factor
-
Journal of Thrombosis and Haemostasis 01/2011; 9(4):881-2. · 5.73 Impact Factor
-
Journal of Thrombosis and Haemostasis 09/2010; 8(9):2066-8. · 5.73 Impact Factor
-
Journal of Thrombosis and Haemostasis 07/2010; 8(7):1641-2. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: International Sensitivity Index (ISI) calibration is based on prothrombin time (PT) determinations in fresh plasma samples of healthy (normal) individuals and patients treated with vitamin K-antagonists (VKA). The ISI is calculated from the slope of the orthogonal regression line of the log(PT) results. The ISI calibration model is based on the assumption that the mean logarithms of the PT's of the normals are found on the orthogonal regression line derived using patients' samples. According to World Health Organization (WHO) guidelines, patients' samples with International Normalized Ratio (INR) beyond the 1.5 to 4.5 interval shall be excluded for ISI calibration. According to the WHO guidelines, outlier samples are defined as those at a perpendicular distance from the orthogonal regression line greater than 3 residual standard deviations, and shall be excluded as well. The purpose of the present study was to assess the effect of sample exclusion on ISI calibration, using the data base of three historic multicenter studies performed in 1990, 1995 and 2005, respectively. Various rules for sample exclusion were tried. In comparison to calibration without any exclusion, between-laboratory variation of the ISI was slightly reduced by sample exclusion using the WHO rule. Furthermore, the adequacy of the ISI calibration model was improved. The effect of the WHO sample exclusion rule on the mean value of the ISI of the current International Standards for thromboplastins was not greater than approximately 1%. It is concluded that the WHO rule for sample exclusion is appropriate for reliable ISI calibration.
Thrombosis Research 06/2010; 125(6):523-8. · 2.44 Impact Factor
-
Journal of Thrombosis and Haemostasis 03/2010; 8(6):1429-30. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The Prothrombin Time (PT) test is used for monitoring of treatment with Vitamin K-antagonists (VKA). The result of the PT test should be expressed as the International Normalized Ratio (INR). Calculation of INR is based on the availability of International Standards (IS) for thromboplastin and a calibration model. Calibration of a new PT test system is performed with the appropriate IS and fresh plasma samples of healthy (normal) volunteers and patients treated with VKA. The calibration model is based on the assumption of a linear relationship between the log(PT)'s obtained with the new PT system and the reference IS for both normal and patients' samples. Patients' samples for calibration should be selected by rejecting samples beyond the 1.5-4.5 INR range. Outliers should be rejected defined as points with a perpendicular distance greater than three residual standard deviations from the line of relationship. Selection of patients' samples and rejection of outliers result in a reduction of the between-laboratory variation of calibration. In addition to monitoring of VKA, the PT is used for management of patients with chronic liver disease. Likewise, INR(liver) should be based on calibration with an IS using samples from patients with chronic liver disease.
Biologicals 03/2010; 38(4):430-6. · 1.70 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Anticoagulant control facilities are being overwhelmed by requests for monitoring and large numbers of patients are not therefore receiving treatment. Procedures designed for point-of-care testing have therefore been developed, the most popular being the CoaguChek. The need for external quality assessment (EQA) of monitors used by patients in self-management has been stressed in a European Commission (EC) Directive. It would not however be feasible for all CoaguChek monitors to be enrolled in national or regional EQA schemes which take time to organise and analyse. The European Concerted Action on Anticoagulation (ECAA) has therefore evolved a simpler system. Its value has been assessed in collaboration with the European Concerted Action on Thrombosis (ECAT). 523 monitors were tested at nine clinics which asked patients to bring their CoaguChek instruments to be assessed with the ECAA/ECAT procedure based on a set of 5 plasma samples with certified international normalised ratios (INR). 15% or more deviation from the certified INR on a single certified plasma sample from the set was defined by the ECAA as the limit of acceptable performance. One hundred and six (20.3%) of the monitors tested showed significant deviation and higher than average incidence of significant INR deviations reported with one specific numbered lot of test strips. Recent ECAA/ECAT, Danish and Italian studies report regular EQA of CoaguChek monitors is essential. There is general agreement that this should be performed at reasonably frequent intervals, at six months or whenever there is a change of the manufacturer's test strips.
Thrombosis and Haemostasis 03/2010; 103(5):936-41. · 5.04 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A model for presenting case histories with quality assessment material is to be developed for the Dutch external quality assessment (EQA) scheme for blood coagulation testing. The purpose of the present study was to assess the performance of clinical laboratories in case-based EQA using the case history of a patient suffering from lupus erythematosus of the skin.
Along with the case history, a freeze-dried plasma sample from the patient was distributed to the participants of the Dutch EQA scheme for blood coagulation testing. The participants were requested to report their coagulation test results, interpretation of the test results, and suggestions for further testing.
The response rate was 65%. Tests for lupus anticoagulant were performed by 27% of the respondents and mixing experiments by 32%. The interpretation of the test results was heterogeneous but the presence of lupus anticoagulant was suggested by 54% of the respondents. A substantial number of respondents (23%) did not provide any interpretation. Only few participants followed the sequential steps for lupus anticoagulant identification recommended by the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis.
Case-based EQA is useful as an educational postanalytical tool. Several limitations were noted, and these included the limited volume of the sample, the different matrix of the freeze-dried sample compared with a fresh sample, and the time lag between the case history and the preparation of the freeze-dried sample.
Journal of clinical pathology 09/2009; 62(8):731-4. · 2.43 Impact Factor
-
L Poller,
C Roberts,
S Ibrahim,
M Keown,
W Ageno, A M H P van den Besselaar,
D Fitzmaurice,
J Harenberg,
S Kitchen,
G Lowe,
M Moia,
G Palareti,
A Tripodi,
A G G Turpie,
J Jespersen
[show abstract]
[hide abstract]
ABSTRACT: Summary Based on the results of the previous European Action on Anticoagulation (EAA) multi-centre study, a simplified minimum procedure is described for screening safety and effectiveness of marketed programs for dosage of oral anticoagulant drugs (vitamin K antagonists). The aim is to demonstrate non-inferiority to the manual dosage at the experienced centres in the European Action on Anticoagulation (EAA) study. Using a cluster sampling procedure a minimum number of centres and minimum total of patients required to establish non-inferiority was determined. At least four centres each recruiting 50 patients over a period of six months is shown to be required (excluding the results from the first 3 weeks' treatment). To achieve non-inferiority the lower 95% confidence interval of the 'time in target INR (International Normalised Ratio) range' (TIR) of a marketed program must be above the TIR limit set by the manual dosage group in the EAA study i.e. 57.5%. The simplified procedure proposed although not an absolute guide to safety is designed to screen against gross unreliability of a test program, without the need to repeat a massive clinical end-point study for each and every program.
Journal of Thrombosis and Haemostasis 08/2009; · 5.73 Impact Factor
-
L. POLLER,
C. ROBERTS,
S. IBRAHIM,
M. KEOWN,
W. AGENO, A. M. H. P. VAN DEN BESSELAAR,
D. FITZMAURICE,
J. HARENBERG,
S. KITCHEN,
G. LOWE,
M. MOIA,
G. PALARETI,
A. TRIPODI,
A. G. G. TURPIE,
J. JESPERSEN,
ON BEHALF OF THE SUBCOMMITTEE ON CONTROL OF ANTICOAGULATION OF THE SSC OF THE ISTH
[show abstract]
[hide abstract]
ABSTRACT: Based on the results of the previous European Action on Anticoagulation (EAA) multicenter study, a simplified minimum procedure is described for screening the safety and effectiveness of marketed programs for dosage of oral anticoagulant drugs (vitamin K antagonists). The aim was to demonstrate non-inferiority to the manual dosage at the experienced centers in the EAA study. With the use of a cluster sampling procedure, a minimum number of centers and a minimum total of patients required to establish non-inferiority were determined. At least four centers, each recruiting 50 patients over a period of 6 months, were shown to be required (excluding the results from the first 3 weeks of treatment). To achieve non-inferiority, the lower 95% confidence interval of the ‘time in target International Normalized Ratio range’ (TIR) of a marketed program must be above the TIR limit set by the manual dosage group in the EAA study, that is, 57.5%. The simplified procedure proposed, although not an absolute guide to safety, is designed to screen against gross unreliability of a test program, without the need to repeat a massive clinical endpoint study for each and every program.
Journal of Thrombosis and Haemostasis 07/2009; 7(10):1736 - 1736. · 5.73 Impact Factor
-
A M H P van den Besselaar
International journal of laboratory hematology 07/2009; 32(2):265-7. · 1.30 Impact Factor
-
S Jowett,
S Bryan,
L Poller, A M H P VAN DEN Besselaar,
F J M VAN DER Meer,
G Palareti,
C Shiach,
A Tripodi,
M Keown,
S Ibrahim,
G Lowe,
M Moia,
A G Turpie,
J Jespersen
[show abstract]
[hide abstract]
ABSTRACT: Increased demand for oral anticoagulation has resulted in wider adoption of computer-assisted dosing in anticoagulant clinics. An economic evaluation has been performed to investigate the cost-effectiveness of computer-assisted dosing in comparison with manual dosing in patients on oral anticoagulant therapy.
A trial-based cost-effectiveness analysis was conducted as part of the EAA randomized study of computer-assisted dosage vs. manual dosing. The 4.5-year multinational trial was conducted in 32 centres with 13 219 anticoagulation patients randomized to manual or computer-assisted dosage. The main outcome measures were total health care costs, clinical event rates and cost-saving per clinical event prevented by computer dosing compared with manual dosing.
Mean dosing costs per patient were lower (difference: euro47) for computer-assisted dosing, but with little difference in clinical event costs. Total overall costs were euro51 lower in the computer-assisted dosing arm. There were a larger number of clinical events in the manual dosing arm. The overall difference between trial arms was not significant (difference in clinical events, -0.003; 95% CI, -0.010-0.004) but there was a significant reduction in events with DVT/PE, suggesting computer-assisted dosage with the two study programs (dawn ac or parma 5) was at least as effective clinically as manual dosage. The cost-effectiveness analysis indicated that computer-assisted dosing is less costly than manual dosing.
Results indicate that computer-assisted dosage with the two programs (dawn ac and parma 5) is cheaper than manual dosage and is at least as effective clinically, indicating that investment in this technology represents value for money.
Journal of Thrombosis and Haemostasis 07/2009; 7(9):1482-90. · 5.73 Impact Factor
-
Journal of Thrombosis and Haemostasis 07/2008; 6(6):1042-3. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In a Dutch project for harmonization of fibrinogen assays, the commutability of potential calibrators for fibrinogen was assessed by means of a twin-study design, which is, in essence, a multicentre, split-patient sample, between-field-methods protocol. The study consisted of simultaneous analysis of fresh-frozen patient plasmas and three potential calibrators for fibrinogen by 48 Dutch laboratories forming 24 couples. The state-of-the-art intralaboratory standard deviation was used to assess the commutability of the potential calibrators. The potential calibrators were commutable for the Clauss, but not for the prothrombin time (PT)-derived assays. One potential calibrator was used in an attempt to harmonize fibrinogen assay results in a Dutch field study. The interlaboratory coefficient of variation (CV) of three out of four test samples could be reduced significantly using the common calibrator. The average overall CV for the four test samples was 10.3% using the routine measurements and 7.8% using the common calibrator. Despite the reduction in the overall CV, the bias between Clauss and PT-derived assay results in two coumarin test samples could not be eliminated.
International journal of laboratory hematology 06/2008; 31(5):513-20. · 1.30 Impact Factor
-
L Poller,
M Keown,
S Ibrahim,
G Lowe,
M Moia,
A G Turpie,
C Roberts, A M H P van den Besselaar,
F J M van der Meer,
A Tripodi,
G Palareti,
C Shiach,
S Bryan,
M Samama,
M Burgess-Wilson,
A Heagerty,
P Maccallum,
D Wright,
J Jespersen
[show abstract]
[hide abstract]
ABSTRACT: Increased demand for oral anticoagulants is overwhelming facilities worldwide, resulting in increasing use of computer assistance. A multicenter clinical endpoint study has been performed to compare the safety and effectiveness of computer-assisted dosage with dosage by experienced medical staff at the same centers.
A randomized study of dosage of two commercial computer-assisted dosage programs (PARMA 5 and DAWN AC) vs. manual dosage at 32 centers with an established interest in oral anticoagulation in 13 countries. The aim was to recruit a minimum of 16,000 patient-years randomized to medical staff or computer-assisted dosage. In total, 13,219 patients participated, 6503 patients being randomized to medical staff and 6716 to computer-assisted dosage. The safety and effectiveness of computer-assisted dosage were compared with those of medical staff dosage.
In total, 13,052 patients were recruited (18,617 patient-years). International Normalized Ratio (INR) tests numbered 193 890 with manual dosage and 193,424 with computer-assisted dosage. The number of clinical events with computer-assisted dosage was lower (P = 0.1), but in the 3209 patients with deep vein thrombosis/pulmonary embolism, they were reduced by 37 (24%, P = 0.001). Time in target INR range was significantly improved by computer assistance as compared with medical staff dosage at the majority of centers (P < 0.001).
The safety and effectiveness of computer-assisted dosage has been demonstrated using two different marketed programs in comparison with experienced medical staff dosage at the centers with established interest in anticoagulation. Significant prevention of clinical events in patients with deep vein thrombosis/pulmonary embolism and the achievement of target INR in all clinical groups has been observed. The reliability and safety of other marketed computer-assisted dosage programs need to be established.
Journal of Thrombosis and Haemostasis 06/2008; 6(6):935-43. · 5.73 Impact Factor
-
Journal of Thrombosis and Haemostasis 10/2007; 5(9):1975-6. · 5.73 Impact Factor
-
Journal of Thrombosis and Haemostasis 08/2007; · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
Journal of Thrombosis and Haemostasis 04/2007; 5(5):1002 - 1009. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A preparation of rabbit brain thromboplastin, provisionally coded 04/162, is proposed as a candidate for the World Health Organization (WHO) International Standard (IS) for thromboplastin (rabbit, plain), meant to replace the IS coded RBT/90 (rabbit, plain), stocks of which are now exhausted.
The preparation was calibrated in an international collaborative study involving 21 laboratories from 13 countries and the calibration was performed against the existing WHO-IS (i.e. rTF/95 and OBT/79) and other Certified Reference Materials from the Institute for Reference Materials and Measurements of the European Commission (i.e. CRM149 S) and from the European Action on Anticoagulation (i.e. EUTHR-01). An additional candidate rabbit brain thromboplastin coded as 04/106 was also included in the study. On the basis of predefined criteria (the within- and between-laboratory precision of the calibration and the conformity to the calibration model), 04/162 was the preferred candidate.
The assigned International Sensitivity Index value was 1.15 and the inter-laboratory SD and coefficient of variation were 0.057% and 4.9%, respectively.
Journal of Thrombosis and Haemostasis 07/2006; 4(6):1339-45. · 5.73 Impact Factor
