Ann Helen Kristoffersen

How to conduct External Quality Assessment Schemes for the pre-analytical phase?

In laboratory medicine, several studies have described the most frequent errors in the different phases of the total testing process, and a large proportion of these errors occur in the pre-analytical phase. Schemes for registration of errors and subsequent feedback to the participants have been conducted for decades concerning the analytical phase by External Quality Assessment (EQA) organizations operating in most countries. The aim of the paper is to present an overview of different types of EQA schemes for the pre-analytical phase, and give examples of some existing schemes. So far, very few EQA organizations have focused on the pre-analytical phase, and most EQA organizations do not offer pre-analytical EQA schemes (EQAS). It is more difficult to perform and standardize pre-analytical EQAS and also, accreditation bodies do not ask the laboratories for results from such schemes. However, some ongoing EQA programs for the pre-analytical phase do exist, and some examples are given in this paper. The methods used can be divided into three different types; collecting information about pre-analytical laboratory procedures, circulating real samples to collect information about interferences that might affect the measurement procedure, or register actual laboratory errors and relate these to quality indicators. These three types have different focus and different challenges regarding implementation, and a combination of the three is probably necessary to be able to detect and monitor the wide range of errors occurring in the pre-analytical phase.

Interpretation and management of INR results: A case history based survey in 13 countries

INTRODUCTION Standardisation of treatment with vitamin K antagonists (VKAs) is still an issue after 60 years of use. The study aimed to explore aspects of VKA monitoring in primary and secondary care. METHODS Two case histories were distributed to physicians in 13 countries. Case history A focused on a patient with atrial fibrillation on stable anticoagulation (latest INR 2.3). Physicians were asked about frequency of INR measurement, when to change the VKA dose, and the patients annual risk of ischemic stroke and bleeding. Case history B focused on a patient with an unexpected INR of 4.8, asking for the patients 48-hour bleeding risk, the immediate dose reduction and time until a repeat INR. RESULTS Altogether, 3016 physicians responded (response rate 8 - 38%), of which 82% were from primary care and 18% from secondary care. Answers varied substantially within and between countries regardless of level of care and VKA used. Median number of weeks between INR measurements was 4 - 6 weeks. Median threshold INR for increasing or decreasing the VKA dose was 1.9 and 3.1, respectively. Risk of ischemic stroke and bleeding were overestimated 2 - 3 times. In case history B, the median dose reduction the two first days was 75% for GPs and 55% for specialists, irrespective of estimates of bleeding risk; with one week to a repeat INR. CONCLUSION Variation in VKA monitoring is substantial implying clinical consequences. Guidelines seem either unknown or may be considered impracticable. Further efforts towards standardisation of VKA management are needed.

An international study of how laboratories handle and evaluate patient samples after detecting an unexpected APTT prolongation

Abstract Background: An unexpectedly detected prolonged activated partial thromboplastin time (APTT) can be a harmless laboratory finding, but can also reflect a thrombotic tendency or a bleeding disorder. The assistance of laboratory professionals in the interpretation of an unexpectedly detected prolonged APTT (uAPTT) is often required. The way in which uAPTTs are evaluated in laboratories was assessed in this international study with the aim of determining whether laboratory professionals are able to fulfill this need. Methods: Postanalytical practices after uAPTT were investigated and the mixing study methodology (if used) was studied by circulating a case report with a questionnaire to staff in the invited laboratories. In addition, the interpretations of those staff regarding the presence or absence of inhibitors in three APTT mixing study scenarios were examined. Results: Large within- and between-country variations were detected in both postanalytical practices and mixing study methodologies among the 990 responding laboratories, 90% of which were in 13 countries. Shortcomings regarding the investigation of uAPTTs leading to potentially incorrect or delayed clinical diagnoses were found in 88% of the laboratories. Of the laboratories to which the interpretative questions were sent, 49% interpreted all mixing study scenarios correctly. uAPTTs were investigated appropriately and all mixing study scenarios interpreted correctly in parallel in only 9.6% of the participating laboratories. Conclusions: The clinical requirement for the assistance of laboratory professionals in the interpretation of uAPTTs cannot be met at most of the participating laboratories. Laboratory professionals should be trained in the evaluation of ordinary laboratory tests, such as that for uAPTTs.

Self-management of warfarin therapy

BACKGROUND Clinical studies from other countries show that self-management of warfarin therapy may reduce the risk of mortality, thromboembolism and complications when compared to conventional therapy. The purpose of this study was to train patients in self-management and compare the results with conventional therapy in Norway. METHOD A total of 23 patients who had previously been given conventional therapy by their GPs were instructed in how to measure INR (using the CoaguChek XS device) and administer warfarin dosage through a structured training programme over the course of 27 weeks. The participants continued with self-management for a further 28 weeks after the end of the training period. The time in the therapeutic range (TTR, measured as a percentage) was calculated and the TTR for conventional therapy and self-management were compared. RESULTS No significant difference in average TTR was found when comparing conventional therapy (70% (95% confidence interval (CI) 62-78)) with the self-management period (75% (95% CI 69-81, p = 0.24)). The percentage of extreme INR values (< 1.5 or > 5.0) was higher during conventional therapy than during self-management (6.8% vs. 1.0%, p < 0.001). INTERPRETATION No significant difference in TTR was found when comparing self-management and conventional warfarin therapy in our study, but for self-management there was a lower percentage of extreme INR values compared to conventional warfarin therapy.

Estimates of Within-Subject Biological Variation of Protein C, Antithrombin, Protein S Free, Protein S Activity, and Activated Protein C Resistance in Pregnant Women

BACKGROUND In pregnancy, interpretation of results from coagulation parameters can be difficult because of the procoagulant physiological changes. The aim of this study was to describe the course of 5 coagulation parameters (thrombophilia markers) in healthy pregnancies, and to estimate and compare the within-subject biological variation (CVI) of these parameters in healthy pregnant and nonpregnant women. METHODS Blood samples were obtained every 4th week during pregnancy and 3 samples after delivery in 20 healthy women and every 4th week during 40 weeks in 19 healthy nonpregnant women. Protein C (PC), antithrombin (AT), protein S free (PS free), protein S activity (PS activity), and activated protein C resistance (with factor V-depleted plasma) (APCR) were analyzed. Before the calculation of CVI, results were transformed into multiples of the median (MoM) and natural logarithm of MoM (lnMoM) to adjust for the physiological changes during pregnancy. RESULTS During pregnancy, PC results showed large variability, AT decreased slightly, and PS free and PS activity decreased significantly. Both activated partial thromboplastin time tests used to calculate APCR decreased, and the APCR ratio was constant. The CVI (lnMoM) in pregnancy were for PC 8.4%, for AT 3.8%, for PS free 11.5%, for PS activity 9.3%, and for APCR 0.5%, and similar to corresponding results in nonpregnant women. CONCLUSIONS Transformation of coagulation parameters in healthy pregnancies to lnMoM is a tool to establish a kind of steady state. Although there is a physiological change in PC, AT, and PS free and PS activity during pregnancy, the CVI was comparable with the CVI of nonpregnant women.

Within-subject biological variation of activated partial thromboplastin time, prothrombin time, fibrinogen, factor VIII and von Willebrand factor in pregnant women

Abstract Background: During pregnancy, interpretation of results from coagulation parameters can be difficult as the physiological changes that occur may affect the biochemical parameters. The aim of this study was to describe the normal course of five coagulation parameters in healthy pregnancies, and to estimate the within-subject biological variation (CVI). Methods: Blood samples were obtained every 4th week during pregnancy and three samples after delivery in 20 healthy women and every 4th week during a 40-week period in 19 healthy non-pregnant women. Activated partial thromboplastin time (APTT), prothrombin time (PT), PT International Normalized Ratio (INR), fibrinogen, factor VIII clot (FVIII:C) and von Willebrand factor antigen (vWF:Ag) were analyzed. The physiological changes during pregnancy were compensated by transformation into multiples of the median (MoM) and it is natural logarithm (lnMoM) in order to establish a kind of steady state, and CVI was calculated from the standard deviation. Results: During pregnancy, APTT, PT and INR remained unchanged or decreased, depending upon the reagent used, while fibrinogen, FVIII:C and vWF:Ag increased gradually until delivery. The CVI in pregnancy were 2.2 and 3.0% for APTT, 2.3 and 2.6% for PT, 2.2 and 2.3% for INR, 7.2% for fibrinogen, 12.2% for FVIII:C and 11.3% for vWF:Ag, and corresponded with the CVI in non-pregnant women. Conclusions: Transformation of coagulation parameters in healthy pregnancies to MoM is a tool to establish a kind of steady state. Although there is a physiological change in these coagulation parameters during pregnancy, the CVI after lnMoM transformation was comparable with the CVI of non-pregnant women.

Warfarin monitoring in nursing homes assessed by case histories. Do recommendations and electronic alerts affect judgements

Abstract Purpose: Older adults treated with warfarin are prone to complications, and high-quality monitoring is essential. The aim of this case history based study was to assess the quality of warfarin monitoring in a routine situation, and in a situation with an antibiotic–warfarin interaction, before and after receiving an electronic alert. Materials and methods: In April 2014, a national web-based survey with two case histories was distributed among Norwegian nursing home physicians and general practitioners working part-time in nursing homes. Case A represented a patient on stable warfarin treatment, but with a substantial INR increase within the therapeutic interval. Case B represented a more challenging patient with trimethoprim sulfamethoxazole (TMS) treatment due to pyelonephritis. In both cases, the physicians were asked to state the next warfarin dose and the INR recall interval. In case B, the physicians could change their suggestions after receiving an electronic alert on the TMS-warfarin interaction. Results: Three hundred and ninety eight physicians in 292 nursing homes responded. Suggested INR recall intervals and warfarin doses varied substantially in both cases. In case A, 61% gave acceptable answers according to published recommendations, while only 9% did so for case B. Regarding the TMS-warfarin interaction in case history B, the electronic alert increased the percentage of respondents correctly suggesting a dose reduction from 29% to 53%. Having an INR instrument in the nursing home was associated with shortened INR recall times. Conclusions: Practical advice on handling of warfarin treatment and drug interactions is needed. Electronic alerts as presented in electronic medical records seem insufficient to change practice. Availability of INR instruments may be important regarding recall time.