PubMed HealthSearch

Biomedical subjects

J M Thomson

Publications and source records attributed to J M Thomson.

At least 19 recordsLinked to original sources

Assessment of value of calibrated lyophilised plasmas to determine International Sensitivity Index for coagulometers.

An attempt was made to correct for the effects of coagulometers on the International Sensitivity Index (ISI) in a series of collaborative studies. Modified ISI were derived from the prothrombin time results with coagulometer systems using a range of calibrated plasmas. Two alternative approaches to correction of the ISI were evaluated. The first relied on the consensus orthogonal regression slopes of the prothrombin times for each coagulometer system plotted against the consensus manual results; the second depended on the local individual slope of the prothrombin times for each instrument. The two procedures were compared with the currently recommended method where International Normalised Ratios (INR) are derived from the manual ISI of the thromboplastin. The recommended method gave a significant bias from the manual results with most coagulometers. In contrast, the local correction procedure gave no significant biases, whereas the consensus method did so in a few instances. Both these correction procedures seem more reliable than the recommended method of INR derivation, but the local correction is more accurate and offers a more practical solution by allowing laboratories to determine their own corrected ISI on a range of calibrated plasmas.

Calibration

Development of physical fitness standards for Canadian Armed Forces younger personnel.

The purpose of this study was to develop minimum physical fitness standards based on common task criteria for personnel younger than 35 years of age in the Canadian Armed Forces. A random sample of 66 men and 144 women performed the Exercise Prescription (EXPRES) test and five physically demanding tasks that simulated common military tasks. Common cutting scores were selected as the point at which 75% of the total weighted sample passed each task. Since there were significant differences between the sexes in task performance and technique execution, the groups were analyzed separately. Results indicated a range in variance of 14 to 48% between military task performance and physical fitness test score, thus suggesting that fitness measures are a poor predictor of task performance. Because of the low variance observed the passing group of each task was treated as a representative sample of subjects whose fitness profiles were indicative of those able to meet task criteria. The 5th percentile fitness scores of the passing group were proposed as the minimum fitness standard. These conditions resulted in fitness standards that were physically more demanding for women than for men.

Adult

The impact of sequential quality assessment exercises on laboratory performance: the multicentre ECAT Angina Pectoris Study. Report from the European Concerted Action on Thrombosis and Disabilities (ECAT).

As an adjunct to a European multicentre prospective study, five quality assessment (QA) exercises, spanning a period of 2.5 years, were undertaken. In these, fifteen laboratories from eight countries each performed ten haemostatic factor assays. The design of the QA exercises allowed the between-duplicate, between-day and between-laboratory coefficients of variation (CVs) to be calculated. The between-duplicate CV decreased by a factor of one quarter, and the between-day CV by a factor of one third, over the five exercises. The activated partial thromboplastin time (APTT) assay consistently showed the lowest CVs, while there was notable improvement in the between-day CVs for von Willebrand factor related antigen (vWF R:Ag) and factor VIII clotting activity (VIII:C). However, the between-laboratory CV, assessing extent of agreement between the different laboratories, did not apparently improve over the five exercises. Thus, while QA exercises may be very useful in improving the performance of haemostatic assays according to criteria which an individual laboratory can assess, improving agreement on haemostatic assay results between laboratories may be more difficult to achieve.

Angina Pectoris

A multicentre study of coagulation and haemostatic variables during oral contraception: variations with geographical location and ethnicity. Task Force on Oral Contraceptives--WHO Special Programme of Research, Development and Research Training in Human Reproduction.

A comparative study of the effects of combined oral contraceptives (OC) on coagulation and fibrinolytic variables using standardized laboratory technique and methodology has been performed in Dublin (Ireland), Salvador (Brazil), Santiago (Chile) and Singapore. Of 777 entrants to the study, 622 were randomly allocated to receive one of four different OC formulations. The remainder did not opt for OC. The progestogenic component was levonorgestrel (LNG) in three of the OC formulations and norethisterone acetate (NEA) in the fourth. Results for the three LNG user groups were pooled. The changes in haematological variables observed over 12 months in the LNG and NEA users were examined in relation to the changes seen in the women not on OC. Women in Salvador differed markedly from those in the other three centres, in showing no acceleration of the prothrombin time and no increase in either fibrin plate lysis or plasminogen following the use of OC. After adjusting the findings in OC users for those in non-users, significant differences in response between centres were also detected for activated partial thromboplastin time (accelerated only in Dublin and Santiago), factor VII activity (increased mainly in Salvador and Santiago) and fibrinogen (for which the most marked changes were an increase in Dublin and a decrease in Salvador). This variability between centres in the effects of OC on coagulation and fibrinolysis suggests that OC administration in different populations may not carry equal thrombotic risks.

Adult

Effects of fixed minidose warfarin on coagulation and fibrinolysis following major gynaecological surgery.

Coagulation and fibrinolytic studies have been performed in patients who were undergoing major gynaecological surgery and randomised to either fixed minidose warfarin (1 mg daily) or matched placebo. With warfarin, a prolongation of the prothrombin time was observed on day 2 which persisted for at least 5 days and was greater than with placebo. The maximal postoperative mean INR was, however, only 1.2 which is considerably less than the target value for prophylaxis of deep vein thrombosis with full dose warfarin. The warfarin group showed two unexpected findings: significantly elevated fibrin specific degradation products throughout the postoperative period compared with placebo and absence of the expected rise of PAI, the major fibrinolytic inhibitor, on the first day after surgery. Levels of fibrinogen degradation products and F1 + 2 prothrombin fragments rose significantly and progressively in both groups in the postoperative period. With placebo, F1 + 2 showed an apparent higher percentage increase on each post-operative day but the differences between the groups were not significant. Increased fibrinolysis may be one of the mechanisms for the protective action of minidose warfarin in prophylaxis of DVT after major surgery.

Adult

Reduction of factor VII coagulant activity (VIIC), a risk factor for ischaemic heart disease, by fixed dose warfarin: a double blind crossover study.

An increase in factor VII coagulant activity is known to be an important risk factor for ischaemic heart disease. Four hundred and eight healthy male Post Office workers were screened in an occupational survey. Sixty eight (16.5%) of these had values of factor VII coagulant activity greater than 1.0 SD above the age related mean. A randomised double-blind crossover study was undertaken to investigate the effect of a fixed daily minidose of warfarin (1 mg) on the high activities of factor VII in these men. Forty two agreed to enter the study and 40 completed it. Their mean factor VII coagulant activity before warfarin treatment was 135.9%. Treatment with a fixed minidose of warfarin significantly reduced factor VII coagulant activity to 124.6%; there was no change on placebo. The prothrombin time was also significantly prolonged on active treatment although all the results remained within the normal range. These findings suggested a fixed minidose warfarin regime might be useful in the primary prevention of ischaemic heart disease by reducing high activities of factor VII.

Adolescent

Automation and prothrombin time: a United Kingdom field study of two widely used coagulometers.

Current performance in the prothrombin time (PT) of the two main United Kingdom coagulometer/thromboplastin systems was assessed in a field survey. Twenty abnormal samples covering a wide spectrum of International Normalised Ratio (INR) were distributed to users of the KC4/KC10 and Coag-a-Mate instruments. Coagulometer results were compared with those of the manual method. A substantial minority with each system showed good agreement with the manual reference values. There was, however, a considerable variation between instruments, meaningful in clinical terms, evidenced by varying regression slopes and local system International Sensitivity Indices (ISI). For intense anticoagulation (3.0 to 4.5 INR) a larger dose of warfarin is needed with the Coag-a-Mate than with the KC instruments. With a manual INR of 4.0 the KC instruments tended to give longer PT (mean INR + 0.3); the Coag-a-Mate PT was generally shorter (mean INR -0.1). With both systems the mean normal PT were shorter than the manual but the degree of shortening did not parallel that of the abnormal samples. This effect undermines the use of a simple prothrombin ratio and of an INR value derived from it, based on a manual ISI. The use of a system related ISI cannot, however, be recommended until local instrument variables are controlled.

Blood Coagulation Tests

The measurement of haemostatic factors in 16 European laboratories: quality assessment for the Multicentre ECAT Angina Pectoris Study. Report from the European Concerted Action on Thrombosis and Disabilities (ECAT).

As part of a European multicentre prospective study involving the measurement of a number of haemostatic factors, a quality assessment (QA) scheme was organized. This paper describes the preparation, design and results of the first QA exercise, involving 16 European laboratories and 10 haemostatic assays. The design allowed the investigation, for each assay, of the variability between duplicates and the variability between days within each centre, and of the agreement between centres. A graphical presentation of each centre's performance in comparison to that of others was adopted, which preserved the confidentiality of each centre's results. The factor VIII clotting activity assay (VIII:C) and the rocket immuno-electrophoresis assays of von Willebrand factor related antigen (vWF R:Ag), antithrombin III, protein C and histidine-rich glycoprotein showed the highest between-duplicate and between-day coefficients of variation (CVs), whereas the clotting assays of activated partial thromboplastin time and fibrinogen had the lowest CVs. CVs for the enzymatic assays using synthetic substrates of antithrombin III, plasminogen and alpha-2-antiplasmin were between these extremes. The between-centre CVs were high for both the VIII:C and vWF R:Ag assays. The QA exercise showed that, in multicentre studies involving the measurement of haemostatic factors, it is feasible to undertake analysis locally at each centre.

Angina Pectoris

Randomized study of adjusted versus fixed low dose heparin prophylaxis of deep vein thrombosis in hip surgery.

A randomized study of adjusted versus fixed low dose heparin prophylaxis has been conducted in 100 patients undergoing surgery for hip replacement or fractured neck of femur. The two types of patients were randomized independently into the adjusted and fixed dose regimens. Patients in the adjusted group were controlled by an activated partial thromboplastin time method particularly responsive to the anticoagulant effect of heparin. The aim was to maintain the peak value just above the upper limit of the normal range. Adjustment of dosage began 24 h after surgery in the replacement group and 24 h after admission in the fracture group. Significant improvement in protection against postoperative deep vein thrombosis, assessed by venography, was observed in the adjusted group undergoing hip replacement (P = 0.013) and overall in both groups (P = 0.017) compared with a conventional fixed dose subcutaneous regimen (calcium heparin 5000 units, 8-hourly). In most instances, adjustment resulted in increased heparin dosage but this was not associated with any evidence of excessive bleeding.

Adult

Isoinertial tests to predict lifting performance.

Previous research has found isoinertial strength testing to be superior to isometric and isokinetic strength testing for prediction of task performance. The purpose of this study was to investigate tests on an isoinertial lifting machine (ILM) and their ability to predict performance on actual lifting tasks. Sixteen male subjects performed two lifting tasks: maximum box lift to truck-bed height of 1.35 m; and 'speed lifts' of 60 concrete blocks (each 22.7 kg) to the same height. These performance tests were compared to three ILM tests: a maximal lift to 1.83 m, a second maximal lift to 1.52 m, and an endurance test that entailed 60 timed ILM lifts of 22.7 kg to 1.83 m. Pearson product-moment correlations between ILM tests and performance tasks varied from r = 0.55 to 0.71. Therefore, the isoinertial test protocols employed in this study were able to account for only 30% to 50% of the variance in the performance of maximal lifting and endurance tasks. In was concluded that prediction of maximal lifting ability or endurance ability using an ILM might be enhanced by closer approximation of specific task variables, or by inclusion of dynamic parameters to measure technique.

Adult

Effect of international sensitivity index (ISI) of thromboplastins on precision of international normalised ratios (INR)

The contribution of the thromboplastin international sensitivity index (ISI) to the interlaboratory coefficient of variation (CV) of the international normalised ratio (INR) with individual reagents was assessed. In theory the precision of the INR should increase with lower ISI values. An empirical relation has been established between the ISI, the INR, and its CV for two rabbit thromboplastins used in sufficient numbers for analysis in the United Kingdom. This was based on the cumulative data from the United Kingdom National External Quality Assessment Scheme (NEQAS) surveys over two years beginning in 1986. The actual precision achieved in NEQAS for the two reagents depends on the ISI value of the thromboplastin and it agreed closely with the figure predicted by the empirical model. The findings show that the ISI value of a thromboplastin strongly influences the interlaboratory variability of the INR obtained with it. The CV of the INR approximates to the CV of the prothrombin ratio multiplied by the ISI. Manufacturers of thromboplastin should therefore be encouraged to produce reagents showing good precision of results reported as simple prothrombin ratios and a low ISI value to avoid impairment in precision when ratio results are transformed to INR.

Animals

Effect of automation on prothrombin time test in NEQAS surveys.

The performance of coagulometers in the National Quality Assessment Scheme (NEQAS) surveys of the prothrombin time conducted between 1986 and 1987 was reviewed. There were sufficient data for analysis for eight types of coagulometer used with a single type of thromboplastin reagent and one instrument with an alternative reagent. The overall reliability efficacy of each instrument was evaluated by determining the orthogonal regression slope parameters for prothrombin time (PT) and international normalised ratios (INR) using the manual technique as the reference method. Seven of the eight types of coagulometer tended to overestimate the INR. A pattern frequently observed with coagulometers, and difficult to regulate, was a trend to underestimate INR below 3.0 and overestimate higher INR. Overestimation of INR values over 3.0 was particularly pronounced with three types of instrument (Fibrintimer, Lancer, KC4/10). The KC4/10 was used by a sufficient number of participants to permit analysis of the performance of individual instruments. Within instrument differences were similar to those produced by different types of coagulometers. Thromboplastin reagents affected the INR values obtained with coagulometers. The study indicates that each local reagent-instrument combination must be calibrated by the participant to obtain reliable INR values. The use of a general correction factor for a local PT system seems to be invalid owing to the considerable variation in performance of individual coagulometers. The two best guides to the choice of coagulometer may be the deviation from the manual result and precision estimated by the coefficient of variation of the INR.

Blood Coagulation Tests

The reliability of international normalized ratios during short-term oral anticoagulant treatment.

The reliability of the international normalized ratios (INR) system in the induction phase of coumarin administration has been studied in 15 serial patients over the first 7-40 days of treatment (mean 13.1). The INR results obtained with a variety of thromboplastin reagents have been compared with those obtained with the WHO second primary IRP, BCT/253. A wide divergence of INR values was observed with the various thromboplastins on each day of testing. INR values cannot therefore be relied upon with some of these reagents in the early days of anticoagulant treatment. This probably arises from the difference in responses of the thromboplastins to depression of vitamin K-dependent clotting factors. Consistent deviations from the IRP suggested that additional error may be due to inaccurate calibration of their products by the manufacturers. When the slopes of the sensitivity of the individual reagents to clotting factors II, VII and X were compared, however, results overall more closely approximated to those of the IRP when the INR were substituted for simple prothrombin ratios.

Acenocoumarol

Survey of prothrombin time in National External Quality Assessment Scheme exercises (1980-87).

National External Quality Assessment Scheme surveys on the prothrombin time test carried out in hospitals in the United Kingdom have been performed at regular intervals since 1972. Performance has been assessed by comparing observed variability between hospitals with that predicted by a statistical model. The model was based on results from 53 survey plasmas issued between 1980 and 1987. These showed a linear correlation between logarithms of mean and standard deviation of reported ratios. Precision improved until the human brain thromboplastin, Manchester Comparative Reagent, was withdrawn in January 1986. There then followed a pronounced overall deterioration which, by October 1987, had not corrected to the levels achieved by 1985. When the recent results from 1986-87 were analysed according to Quick test reagent only one reagent (ISI 1.1) showed an improvement in precision. Performance of the other Quick test reagents, all with higher ISI values, had not regained the standards of precision previously achieved by the human brain reagent.

Animals

NH4+ transport in acid-secreting insect epithelium.

The relationship between ammonia secretion (JAmm), hydrogen ion secretion (JH), and intracellular pH (pHi) was investigated in isolated locust (Schistocerca gregaria) rectal epithelia mounted as flat sheets in specially designed Ussing chambers. In the absence of exogenous CO2 and ammonia, the rectum is capable of net acid and ammonia secretion into the lumen against pH gradients of up to 1.8 U. JAmm was dependent on the presence of luminal amino acids and Na+ and it was relatively unaffected by K+ removal or changes in membrane potential. JAmm and pHi remained fairly constant over a luminal pH range of 7-5, whereas JH decreased linearly to zero over the same pH range. Mucosal addition of 1 mM amiloride reduced JAmm by 60%. This study demonstrates that the locust rectum secretes significant quantities of endogenously produced ammonia preferentially into the lumen as NH+4 rather than NH3. Moreover, the results suggest that the ammonia crosses the apical membrane via an amiloride-inhibitable Na+-NH+4 exchange mechanism.

Amiloride

Fixed minidose warfarin: a new approach to prophylaxis against venous thrombosis after major surgery.

A prospective study was carried out to see whether a small fixed dose of warfarin (1 mg daily) given before operation (mean 20 days) would prevent deep vein thrombosis in patients having major gynaecological surgery. One hundred and four patients were randomised into three groups: fixed minidose warfarin; full dose oral anticoagulation; and no treatment (controls). There was a significantly lower incidence of deep vein thrombosis in the minidose warfarin and full dose anticoagulant treatment groups (9% (3/32) and 3% (1/35) respectively) than in the controls (30%; 11/37) but no significant difference between the two anticoagulant treatment groups. Prothrombin time and the activated partial thromboplastin time were normal on the day of surgery in the warfarin treatment group, whereas times were prolonged in the group given full dose anticoagulation. Mean haemoglobin concentrations fell in all three groups after operation but the fall was significantly less in the minidose warfarin treatment group than after full dose anticoagulation. The benefit from full dose oral anticoagulant prophylaxis, based on a preoperative international normalised ratio of 1.5-2.5 with rabbit brain Manchester reagent, was similar to the protection achieved in an oral anticoagulant treatment group controlled with human brain Manchester comparative reagent at a similar level of anticoagulation. The lack of disturbance of normal haemostasis at the time of operation together with a significant reduction in deep vein thrombosis may encourage surgeons to introduce minidose prophylaxis with warfarin.

Adult

Protein C response to induction and withdrawal of oral anticoagulant treatment.

Protein C activity and antigen levels have been related to clotting activities of factors VII and X during the induction and withdrawal periods of oral anticoagulant treatment. Both factor VII and protein C activities fell rapidly during induction but factor VII showed a more rapid and much more marked depression than protein C. In contrast, reductions in factor X were much slower. Protein C antigen, although depressed rapidly at the initiation of treatment, did not subsequently fall to the same degree as protein C activity. The ratio of activity to antigen became progressively smaller. On discontinuation there was a reversal of the pattern but with two important differences. Firstly, there was evidence of an excessive rise ('rebound') of factor VII compared with the steady state levels in these patients; and secondly there was a surprisingly slow return of protein C to normal levels after the oral anticoagulant was withdrawn (levels were still below normal on day 4). These observations lend support to gradual withdrawal of oral anticoagulants after a period of long-term administration. The results suggest that after discontinuation of long-term anticoagulants patients may have increased coagulability up to four days.

Acenocoumarol