A survey of coagulation laboratory practices and satisfaction ratings of member laboratories of the Thailand National External Quality Assessment Scheme for blood coagulation.

INTRODUCTION: The Thailand National External Quality Assessment Scheme (NEQAS) for blood coagulation was established in 2005. The objective of this study was to collect data of coagulation laboratory practices and satisfaction of NEQAS member. METHODS: Two hundred seventy-six questionnaires were sent to laboratories that are members of NEQAS to obtain data relating to coagulation laboratory practice and satisfaction in 2014. Data from this survey were compared with data from the survey conducted in 2005 to evaluate levels of improvement. RESULTS: Of 276 questionnaires sent, 212 (76.8%) were returned. Improvements were characterized by the number of laboratories that (i) decreased use of 3.8% sodium citrate as anticoagulant; (ii) implemented use of at least two control levels for internal quality control; and (iii) implemented reporting of reference values with results, as well as establishing their own reference range and using geometric mean as the denominator for international normalized ratio calculation. For overall satisfaction, 179 of 206 (86.9%) participant laboratories reported being satisfied or very satisfied. CONCLUSION: Improvements in coagulation laboratory practices in Thailand were observed in every step of the total testing process. However, additional improvements are still needed, such as determination and use of a local reference range.

Establishing an external quality assessment scheme for point-of-care international normalized ratio in Thailand.

INTRODUCTION: Effective warfarin therapy management has gained national interest, resulting in the increased use of point-of-care testing (POCT) for international normalized ratio (INR). External quality assessment (EQA) is recommended to ensure quality of the testing. CoaguChek XS and CoaguChek XS Plus are the only commonly available POCT INR monitors in Thailand. Therefore, Thailand NEQAS for Blood Coagulation initiated the scheme for POCT INR in 2013, including only hospitals using these devices. METHODS: Questionnaires were sent to the hospitals, enquiring about their interest in EQA participation. Two surveys were distributed; each included five certified European Concerted Action on Anticoagulation (ECAA) INR plasma sets. Unsatisfactory performance was indicated by a 15% deviation from the certified mean INR value. RESULTS: There were 156 hospitals using the devices. Thirty-five hospitals responded to the questionnaires. Medical personnel undertaking POCT INR were limited to laboratory staff in 29 (83%) of these centers, and 31 hospitals actually participated. The medians of results from participants were the same or nearly the same as the certified mean INRs. CONCLUSION: External quality assessment for POCT INR in Thailand is feasible using the ECAA plasmas as control materials. The results therefore appear encouraging to other developing countries to establish their own EQA schemes.

Current practices of bleeding time in a developing country: an alert for noncompliance with the standard procedures.

INTRODUCTION: Bleeding time is still widely performed in many developing countries including Thailand. To generate an accurate result, the procedure should be complied with standard recommendations such as those from Clinical and Laboratory Standards Institute (CLSI) and World Federation of Hemophilia (WFH). The authors surveyed the current practices of bleeding time in Thailand in order to verify the practices that did not comply with the accepted standard. METHODS: The questionnaires were sent to hospitals participating Thailand National External Quality Assessment Scheme (NEQAS) for blood coagulation. Items in the questionnaire comprised information about preanalytical, analytical, and postanalytical issues of bleeding time. RESULTS: From a dispatch of 201 questionnaires, 155 (77.1%) were returned. The common noncompliance with standards observed in this survey included inappropriateness of indication, e.g. use for preoperative screening (95 of 126, 75.4%), use of devices other than standard template (130 of 132, 98.5%), and inappropriate reference range (125 of 127, 98.4%). CONCLUSIONS: The noncompliance shown in this survey can affect the accuracy of bleeding time results. The authors would like to address these problems as an alert for other laboratories especially in the developing countries where the standard templates are not widely available.

Evaluation of Thrombi-Stat MC1 for whole blood and plasma international normalized ratio in comparison with a laboratory method.

INTRODUCTION: The precision and comparability of the international normalized ratio (INR) analyzed by the Thrombi-Stat MC1 coagulation testing system were evaluated before using as a point-of-care testing. METHODS: Three levels of control materials were used for within-run and between-run precision study. Comparison study of INR determination from citrated whole blood (INR-WB) and citrated plasma (INR-PL) analyzed by the Thrombi-Stat MC1 with those by the validated method, Sysmex® CS-2100i (INR-CS), was performed. RESULTS: The within-run coefficient of variations (CVs) of INR by the Thrombi-Stat MC1 were 3.60% to 4.80%. For between-run precision, the CVs were 4.26 to 4.93%. Fifty-four plasmas from patients receiving warfarin were included for comparability testing. There were good correlation and agreement between both INR-WB and INR-PL compared with INR-CS. Eighty-seven percent of INR-WB and 100% of INR-PL were within ± 0.5 units of the INR-CS. Given that the therapeutic range was INR-CS of 2-3, 3.7% of INR-WB and 5.56% of INR-PL were discordant with the INR-CS. CONCLUSION: The precision and comparability to validated method of the Thrombi-Stat MC1 were acceptable. Either citrated whole blood or plasma may be used as samples in this system. Impact on the management of patients must be taken into consideration prior to the implementation of this system.

Inappropriate use of protein C, protein S, and antithrombin testing for hereditary thrombophilia screening: an experience from a large university hospital.

INTRODUCTION: Deficiencies of protein C, protein S, and antithrombin are the main inherited risk factors in Thai patients with venous thromboembolism, although the prevalence is not high. METHODS: To evaluate the appropriate use of the testing for these proteins, the test orders of 503 patients were retrospectively reviewed using the proposed guidelines. Inter-rater reliability between two investigators was also calculated. RESULTS: Of 503, 459 (91%; 95% confidence interval 88-93%) of the test orders were inappropriate. The most common cause of inappropriateness was testing during acute thrombosis (42.5%). Results were inconclusive in 105 (20.9%) patients who had isolated decrease in one of the proteins, mostly owing to lack of confirmation of the abnormal results. Kappa index for the reliability of two investigators was 0.79. CONCLUSION: To enhance the appropriate use of hereditary thrombophilia screening tests, physician education concerning the patient selection, suitable timing for testing and repetition of the tests with abnormal results should be emphasized.

Application of indicators for quality improvement in the coagulation laboratory.

Indicators are tools that measure work performance and serve as a guide to improve the quality of laboratories. Seven Indicators for quality improvement have been established in our coagulation laboratory. They are :- 1). percentage of pre-analytical problems, 2). personnel competency scores, 3). results of external quality assessment, 4). % coefficient of variation (CV) of control materials, 5). unit cost, 6). percentage of reports within determined time, and 7). percentage of customers who were satisfied. The percentage of preanalytical error gradually decreased from 1.8% in April 2001 to 0.8% in June 2001 as a result of co-operation between the coagulation laboratory and the wards. Since there is no system to check personnel competency at a national level in Thailand, we set up a program for testing personnel competency in our department by asking every technician to take a written and practical laboratory examination. The scores achieved by our personnel ranged from 40 to 90%. For those who achieved scores of lower than 70%, we limited their responsibilities and organized a training program for them. In order to check our laboratory's accuracy, we are enrolled in the WHO International External Quality Assessment Scheme (IEQAS) in Blood Coagulation and have been since 1987. The survey results indicated that most of our laboratory tests were within consensus including our homemade ELISA tests for protein C, protein S and vWF antigen. The percent CVs of control materials used for the internal daily control for every test were analyzed. They ranged from 2.3 for normal APTT to 11.4 for the low level of free protein S in plasma. The unit cost for each test was analyzed to determine the cost-effectiveness of the laboratory. We set the goal for the turn around time for emergency coagulation tests to be within an hour and the percentage of reports within this time was 91.6% in August 2001. The last indicator was the percentage of satisfied customers, which gave an indication of the quality of all Out Patient Department (OPD) services performed by our department. We sent 400 questionnaires to doctors, nurses and patients in OPD asking their opinion of both the technical services and the behavior of our technicians. The percentage satisfaction of our customers concerning services offered to OPD was lower than 50%. We plan to improve the last 2 indicators by expanding the space of the OPD/emergency laboratory and reorganizing the service system. All indicators mentioned above have helped to improve the quality of our laboratory greatly.

Detection of haemoglobin variants and inference of their functional properties using complete oxygen dissociation curve measurements.

Complete oxygen dissociation curves for red cell suspensions of three haemoglobinopathies, namely haemoglobin (Hb) H, Hb Köln and Hb Tak/beta thalassaemia diseases, were measured using automatic recording methods. These curves were left-shifted compared with the normal red cell curve and showed a biphasic shape as a result of co-existence of the high and normal affinity haemoglobin components. Computer-assisted simulation of these biphasic curves enabled us to infer the curves for the pure abnormal haemoglobins and their fraction in the total haemoglobin of the red cell. The inferred values of fraction agreed with those determined by haemoglobin type analysis or the literature values. The curve for Hb Köln red cells deviated from the normal red cell curve in the whole range of oxygen saturation, whereas the curve for Hb H was close to the normal curve at the middle and upper portions. This difference in deviation was ascribed to a possible interaction between Hb Köln and Hb A through subunit exchange, and its absence between Hb H and Hb A. The present results indicate that measurement of the complete oxygen dissociation curve is important for the detection of non-interacting variants such as Hb H and is useful for inferring the functional properties of haemoglobin components that are not easily isolated.

Hemostatic alterations in beta-thalassemia/hemoglobin E patients.

To search for evidence of coagulation activation ex vivo, the levels of human prothrombin fragment 1+2 (F1+2) were examined in 69 beta-thalassemia/Hb E patients. Levels of protein C inhibitor (PCI) and activated protein C - PCI (APC:PCI) complex were also determined in 9 of the above patients in conjunction with protein C (PC) antigen and activity, in an attempt to detect increased consumption of PC. In mean level of F1+2, there was a statistically significant difference between normal control and post-splenectomized patients (p < 0.05) but not between normal control and non-splenectomized patients (p > 0.05). The mean levels of PC activity and PC antigen in the patients were much lower than in normal controls. However, the mean levels of PCI and the mean level of APC:PCI complex in the patients were not significantly different from those in normal controls (p > 0.05). The high level of F1+2 in post-splenectomized patients found in this study agreed well with clinical and other laboratory findings. The normal level of PC inhibitor and APC:PCI complex found in this study provided no evidence of increased consumption of protein C in thalassemia patients.

Effect of different oral anticoagulant intensities on prothrombin fragment 1 + 2 in Thai patients with mechanical heart valve prostheses.

The minimal intensity of oral anticoagulant required for antithrombotic protection in patients with a mechanical heart valve is still debatable, and that of the Westerner may not be directly applied to Thai patients. Our preliminary clinical review suggested that International Normalized Ratio (INR) 2-3 might be enough but it needs further supporting evidence. Therefore, we studied the effect of different anticoagulant intensities, expressed as INR, on the in vivo coagulation activation by measuring prothrombin fragment 1 + 2 (F1 + 2) in 116 patients with mechanical heart valve replacements. The patients had received warfarin for not less than one month with different intensities. The mean +/- S.D. of F1 + 2 level in 30 normal controls was 0.7 +/- 0.17 nmol/L. After excluding two outliers, the maximum linear correlation between INR and F1 + 2 was -0.658 (p < 0.001) when only patients whose intensities were lower than INR3 were taken into account. Adding more data from the patients having higher intensities decreased the correlation coefficient. The patients were subsequently classified by INR values in the range INR 1.1-1.9, 2-3 and 3.1-4.2. The F1 + 2 in each group was 0.6 +/- 0.30, 0.28 +/- 0.13 and 0.24 +/- 0.13 nmol/L respectively. The F1 + 2 in the first group did not differ from normal (p = 0.119) but was higher than the others (p = 0.000). The latter two groups had no difference between them (p = 0.112). Hence, from the laboratory point of view, we did not see additional benefit in the reduction of thrombin activation by the anticoagulant intensities higher than the range INR 2-3. The evidence supported that this therapeutic range might be enough for Thai patients with mechanical heart valves.