E. Witteveen

A comparison between capillary and venous blood international normalized ratio determinations in a portable prothrombin time device.

The CoaguChek® PT system is a portable point-of-care device for prothrombin time testing that can be used with capillary and venous whole blood. This system had been calibrated by the manufacturer in terms of the international normalized ratio (INR) for monitoring oral anticoagulant therapy. The purpose of the present study was to compare capillary blood with venous blood INRs from healthy volunteers and patients treated with oral anticoagulants using the same CoaguChek® PT system. Two different CoaguChek® PT strip formulations [international sensitivity index (ISI), 1.5 and 1.1] were used in separate test series. The differences between capillary and venous blood INRs were statistically significant (P < 0.001) but the magnitude of the differences was small. The mean relative deviations of the INR were 5.8 and 2.8% for the strips with ISI 1.5 and 1.1, respectively. These deviations are clinically acceptable. It is concluded that capillary blood can be replaced by venous blood for the calibration of the CoaguChek® PT system.

Influence of haematocrit on international normalised ratio (INR) differences between a whole blood point-of-care coagulation monitor and reference prothrombin time in plasma

The CoaguChek S system is designed for use in patient self-testing. In this system a whole blood sample without sodium citrate is applied to a test strip containing thromboplastin and iron oxide particles. The detection principle is based on fibrin formation which inhibits and finally stops the movement of the iron oxide particles. In the classic prothrombin time (PT) test, citrate plasma is mixed with thromboplastin and an excess of calcium ions. In the monitoring of vitamin K-antagonist (VKA) treatment, all results are expressed on a common scale, i.e. international normalised ratio (INR). In patients on long-term VKA treatment, INRs were determined by the CoaguChek S system and reference methods for the classic PT. Four different CoaguChek S strip lots were evaluated. The difference in INR between the reference PT and the CoaguChek S system was negatively correlated to the haematocrit of the patients. We conclude that INR differences between CoaguChek S and plasma PT may be explained in part by the haematocrit. The magnitude of the effect of haematocrit, within the reference interval of 0.37 - 0.51, on the INR difference was not greater than approximately 10% for the combined data of the four strip lots. A bias of less than 10% seems to be acceptable clinically.

Point-of-care monitoring of vitamin K-antagonists: validation of CoaguChek XS test strips with International Standard thromboplastin

Aims Many patients treated with vitamin K-antagonists (VKA) use point-of-care (POC) whole blood coagulometers for self-testing. The majority of patients in the Netherlands use one type of POC coagulometer, that is, the CoaguChek XS. Each new lot of test strips for the CoaguChek XS is validated by a group of collaborating thrombosis centres. We assessed the International Normalised Ratio (INR) differences between each of 51 new lots of test strips and the International Standard for thromboplastin rTF/95 or its successor rTF/09. Methods Each year, a particular lot of CoaguChek XS test strips was used as reference lot. The reference lot was validated by comparison to the International Standard, yielding a relationship between the reference lot INR and International Standard INR. Successive lots of test strips were compared to the reference lot by three centres using 19–29 capillary blood samples obtained from VKA-treated patients. Each patient provided two blood drops from the same finger prick, one for the reference lot strip and one for the new lot. Results The mean INR differences between each lot and the International Standard varied between −8% and +4%. The mean absolute values of the relative differences varied between 2.4% and 8.1%. There were small but clinically unimportant differences in INR between the first and second drop of blood. Conclusions Accuracy of CoaguChek XS INR determinations can be assessed by a group of collaborating centres using a limited number of capillary blood samples. As the mean INR differences with the International Standard were smaller than 10%, the lots were approved for use by the Netherlands Thrombosis Services.

International Collaborative Study for the Calibration of a Proposed International Standard for thromboplastin, human, plain: International standard for thromboplastin

Summary. Background: 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. Results: 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. Conclusions: 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.

Influence of Blood Collection Systems on the Prothrombin Time and International Sensitivity Index Determined With Human and Rabbit Thromboplastin Reagents

Three brands of blood collection tubes were studied for their influence on the prothrombin time (PT) and international sensitivity index (ISI) for 5 commercial thromboplastin reagents. With all reagents, PTs were shorter in Vacutainer (Becton Dickinson Vacutainer Systems, Plymouth, England) samples than in S-Monovette (Sarstedt, Nümbrecht, Germany) or Venosafe (Terumo Europe, Leuven, Belgium) samples. ISI values were higher with Vacutainer samples than with S-Monovette or Venosafe samples. The ISI differences between the tubes were small for Thromborel-S (2.1%; Dade Behring, Marburg, Germany) and Hepato Quick (1.1%; Diagnostica Stago, Asnières, France; Roche Diagnostics Nederland, Almere, the Netherlands) but greater for Neoplastin Plus (5.5%; Diagnostica Stago; Roche Diagnostics Nederland), Simplastin HTF (8.3%; bioMérieux, Durham, NC), and Innovin (8.8%; Dade Behring). The PT and ISI differences between the tubes could be explained mostly by the effect of magnesium ion contamination in the sodium citrate solutions. When PT ratios were transformed into international normalized ratios (INRs) using crossover ISI (ie, samples collected with one type of tube and ISI determined with another collection system for the PT reagent), the differences in mean INRs could be approximately 10%. For ISI calibration of reference thromboplastins, blood collection tubes should be used with minimal divalent metal ion contamination of the citrate solution.

Influence of plasma volumetric errors on the prothrombin time ratio and International Sensitivity Index.

The International Sensitivity Index (ISI) for prothrombin time systems depends on the thromboplastin manufacturers recommended method for use. The purpose of the present study was to investigate the influence of small deviations from the recommended sample volume on the prothrombin time ratio and ISI. Four commercial reagents were studied; three with low ISI and one with high ISI. The effects of volumetric errors on the ISI were used to assess the associated effects on the International Normalized Ratio (INR). The effect of 10% volume error on the INR was not greater than 5%. The effects with the three low-ISI reagents were slightly greater than those with the high-ISI reagent. It is recommended that each laboratory should check the volumes of sample and reagent used for the prothrombin time test.