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Biomedical subjects

J M Thomson

Publications and source records attributed to J M Thomson.

At least 55 records · Page 3Linked to original sources

Questions and answers on prothrombin time standardisation in oral anticoagulant control.

One of the reasons why oral anticoagulants fell into disrepute is the absence of internationally accepted standardised procedures for controlling the level of anticoagulation. This deplorable situation resulted in over- and under-coagulation and uncertainty in the therapeutic range. International conformity can now be obtained by using an International Normalised Ratio (INR) which is derived from the individual result obtained in a given plasma sample and the International Sensitivity Index (ISI) of the tissue thromboplastin reagent used. Any thromboplastin reagent can be calibrated against an international primary or secondary W. H. O. reference preparation, so as to obtain its International Sensitivity Index. The new system of reporting the level of anticoagulation was designed and can only safely be applied in patients taking oral anticoagulants.

Administration, Oral↗

The calibration of the second primary international reference preparation for thromboplastin (thromboplastin, human, plain, coded BCT/253).

An international collaborative exercise has been undertaken to calibrate a replacement for the first WHO primary international reference preparation (IRP) for thromboplastin. The replacement preparation is a lyophilised batch of British Comparative Thromboplastin (BCT/253, human plain) for use in the Quick prothrombin time test. Seventeen centres participated. The experimental design, calibration model and statistical analysis were based on the recommended WHO procedure. As a result of this calibration exercise an International Sensitivity Index (ISI) of 1.1 has been assigned to the preparation by WHO and it has been officially recognised as the second primary IRP for thromboplastin. The calibration of BCT/253 is an essential link in a new hierarchical structure for the standardisation of the prothrombin time. The aim is to provide a uniform international system of reporting prothrombin time results using International Normalised Ratios (INR) derived from the ISI of individual thromboplastins.

Humans↗

The bleeding time: current practice in the UK.

A questionnaire survey of current practice in the bleeding time test has been undertaken by the UK External Quality Assessment Scheme in blood coagulation. Completed returns have been received from 358 centres. Most centres (88.5%) perform bleeding times and of these the Ivy test is the most commonly performed. Only 13.6% perform the Duke method. Templates are used to control the procedure by approximately half of the hospitals. There is considerable variability in the type and depth of incision and interpretation of the endpoint. The upper limit of normality not unexpectedly differs considerably between the centres with both Ivy and Duke methods. The use of a commercial template method, 'Simplate', provides a measure of agreement amongst the group of hospitals using this instrument but it remains to be established whether this is the most reliable procedure. In the interim, gross discrepancies in technique or interpretation should be corrected in the light of the findings of the survey.

Bleeding Time↗

Lipid class composition and heparin sensitivity in the activated partial thromboplastin time.

In an APTT reagent, prepared from purified lipids, the role of phosphatidyl serine (PS) in determining the sensitivity of the APTT test system to measurement of the effect of heparin in plasma has been evaluated. As the concentration of PS decreases sensitivity to heparin increases but procoagulant activity decreases. Dilution of the test liposome over a wide range (1 g/l to 30 mg/l) had a minimal effect on the clotting time. At levels below 30 mg/l, however, the amount of total lipid appeared to be rate limiting; a loss of procoagulant activity being paralleled by an increase in heparin sensitivity. Phosphatidyl inositol (PI) was not a satisfactory substitute for PS in the APTT method studied. The degree of unsaturation of test liposomes appeared to have no effect on either procoagulant activity or sensitivity to heparin at the lipid concentration employed. In the light of these findings, a more critical appraisal of the phospholipid components of APTT reagents should facilitate the development of more reliable reagents for heparin control. A further benefit of this type of approach should be a reduction in the acknowledged wide variations in sensitivity to heparin which exist between available APTT reagents.

Blood Coagulation Tests↗

The use of Vacutainer tubes for collection and storage of blood for coagulation testing.

A study has been performed to evaluate the suitability of Vacutainer tubes in blood specimen collection for coagulation tests and to compare them with the conventional syringe technique employed in UK hospitals. Blood was collected from healthy volunteers, an ante-natal group and patients on long-term oral anticoagulants. Samples were stored at two different temperatures; 4 degrees C and ambient room temperature (RT). Prothrombin times, factor VII assays and APTT were performed at baseline and after 2 h and 4 h storage. There was significant activation of the extrinsic system in the blood samples collected by Vacutainer when stored at 4 degrees C which became more significant on prolonged storage. The effect was less pronounced when the Vacutainer tubes were stored at RT. In contrast, the blood collected by the syringe method did not show these changes with the exception of the ante-natal specimens where a lesser degree of activation than in the Vacutainer tubes was observed after 4 h at 4 degrees C. The activation of the Vacutainer samples at 4 degrees C is considered undesirable and could be of clinical significance in oral anticoagulant dosage.

Blood Coagulation Tests↗

O2 transport during exercise following blood reinfusion.

Reasons for an increase in maximal O2 consumption (VO2max) following blood reinfusion remain unclear; thus the present investigation was undertaken to examine the arterial and femoral venous blood gases during submaximal and maximal exercise. Four untrained males (22-25 yr) performed modified Balke work capacity tests under control conditions (Hct = 42.4 +/- 0.8%; Hb = 14.7 +/- 0.5 g X 100 ml-1) and following autologous blood reinfusion (Hct = 46.2 +/- 1.3%; Hb = 16.4 +/- 0.9 g X 100 ml-1). VO2 was determined by open-circuit spirometry and cardiac output by the N2O method; radial arterial and deep femoral venous blood were sampled at each work load throughout the incremental work tests. Following blood reinfusion, subjects' VO2max increased (P less than 0.05) from 4.0 (in control) to 4.5 1 X min-1. Throughout submaximal exercise arterial PO2 remained relatively constant (between 80.1 +/- 4.4 and 89.1 +/- 5.0 Torr) and cardiac output unchanged, comparing the two experimental conditions. Femoral venous PO2 values were almost identical throughout the work capacity tests, declining at exhaustion to 15.7 +/- 1.5 Torr in control and to 13.8 +/- 3.3 Torr postreinfusion. It appeared that the subjects' increase in VO2max postreinfusion was due to an increased O2 supplied to the tissue [i.e., cardiac output (Q) X arterial O2 content (CaO2)] by the central circulation. This resulted from a small (10%) increase in Q and a constant elevation in CaO2 of 1.7-2.2 ml X 100 ml-1, since virtually no changes were observed in the femoral venous blood postreinfusion and the acid-base status and temperature, important determinant of O2 dissociation, were (almost) identical, comparing the two experimental conditions.

Acid-Base Equilibrium↗

An evaluation of chromogenic substrates in the control of oral anticoagulant therapy.

A comparison has been made between the prothrombin time test using British Comparative Thromboplastin (BCT) and four modified amidolytic assays in the assessment of laboratory control of oral anticoagulant administration in short-term and long-term patients. The results were also correlated with the APTT and specific assays for factors VII and X based on established coagulation techniques. The chromogenic substrate assays did not give as close agreement with the BCT as the clotting assays for factors VII and X. A combination of the amidolytic factor II and X results did not improve the correlation. Agreement with the BCT was better in long-term patients with the substrates but there was no obvious advantage between the factor II and X amidolytic methods in this group. The development of a specific amidolytic assay for factor VII should be considered based on the evidence of this study although its reliability for oral anticoagulant control would need to be validated by clinical trial. In the interim, it may be anticipated that thromboplastins showing less sensitivity than BCT to factor VII would give a better correlation with the amidolytic assays.

Acenocoumarol↗

An assessment of an amidolytic assay for factor VII in the laboratory control of oral anticoagulants.

A comparison has been made between the prothrombin time test using British Comparative Thromboplastin (BCT) and a chromogenic substrate assay for factor VII in the assessment of laboratory control of oral anticoagulants in short-term and long-term patients. Opportunity was also taken to compare the findings with parallel results obtained with the venous Thrombotest technique and a specific clotting assay for factor VII. There was good agreement between the amidolytic factor VII assay, using a method modified from Seligsohn et al (1978) with the Quick test using BCT and Thrombotest in 60 long-term patients. Tests in 53 patients within the first 3 weeks of starting oral anticoagulant administration gave less satisfactory agreement between the above amidolytic method and the conventional tests. In contrast, there was a good correlation between the two conventional tests in both groups and also between the clotting and amidolytic factor VII method. Although the results are an improvement on previous, less satisfactory correlations between the BCT prothrombin time method and amidolytic assays for factor II and X, the present study indicates the limitations of a specific clotting assay versus a broad spectrum extrinsic clotting test in oral anticoagulant control. While not warranting the routine use of the chromogenic assay for factor VII in place of the prothrombin time using BCT, the factor VII amidolytic assay offers a limited but dependable guide to dosage in long-term patients. The complexity of the technique in its present form militates against its adoption for routine anticoagulant control in hospital laboratories.

Acenocoumarol↗

Prostacyclin-like, and kallikrein activity of amniotic fluid in pre-eclampsia.

Amniotic fluid from patients with pre-eclampsia was compared with samples obtained from normotensive controls with respect to the inhibiting effect on platelet aggregation (PGI2-like activity) and activating effect on the plasma kallikrein assay and Russell's viper venom test. After 39 weeks gestation, amniotic fluid from pre-eclamptic patients showed significantly less PGI2-like activity ( p less than 0.01) and significantly lower kallikrein levels (p less than 0.01) than that from normotensive controls. The study suggests that the biosynthesis and release of PGI2-like activity and kallikrein may be impaired in pre-eclampsia. In view of the association of pre-eclampsia with intravascular clotting, the highly significant reduction of PGI2-like activity seems important and appears to warrant a clinical trial of prostacyclin administration in this disorder.

Amniotic Fluid↗

Prediction of anaerobic capacity: a performance test employing an optimal exercise stress.

Highly trained sprinters, marathon runners, and untrained male subjects sprinted around a 400-metre track with their running times and speeds throughout the sprint being continuously monitored. Through comparison with their individual anaerobic capacities (previously determined in the laboratory), a performance test was developed for predicting subjects' anaerobic energy expenditure. The format of this test imposed an optimal stress upon the anaerobic energy components through a combination of work intensity and prolongation of the exercise stress. Specifically, through multiple regression analysis, it was determined that the sprinting time to 256-metres and running speed from 256-metres through 329-metres provided the highest predicting of anaerobic capacity (significant at the 0.01 level of confidence).

Adult↗

A laboratory method for determination of anaerobic energy expenditure during sprinting.

Highly trained sprinters, marathon runners and untrained male control subjects were studied during treadmill sprinting. After confirming a workload which elicited exhaustion in just over a minute (mean time to exh. = 64.6 +/- 2.5 sec.), each subject performed sprints of 15, 30, 45 and 60 seconds duration in order that their energy expenditure could be segmented per 15-sec. of sprinting time. During every sprint, O2 consumption was recorded by closed-circuit spirometry. Following each sprint, serial 30-sec. venous blood samples were drawn in order to determine the peak lactate concentration. Energy expenditure was therefore determined as follows: i) aerobic energy from increments in O2 uptake, expressed in Kcal; ii) lactacid energy from increments in peak lactate, with the difference between peaks utilized to calculate the anaerobic glycolytic contribution to that 15-sec. segment, expressed in Kcal according to Margaria; iii) alactacid energy, expended over the initial 15-sec. segments, from the difference between the total energy requirement per 15-sec. less the measured aerobic plus the lactacid contributions. The sprinters expended the greatest (p less than .05) anaerobic energy (46.2 +/- 5.1 Kcal) when compared to either the marathoners (31.6 +/- 5.7 Kcal) or controls (33.0 +/- 1.6 Kcal). The athletic groups demonstrated superior alactacid energy (sprinters = 21.4 +/- 4.4 Kcal; marathoners = 15.8 +/- 2.3 Kcal), both expending a substantial amount of energy from this source (20%) past 30-sec. In contrast, over the initial 30-sec. of sprinting, the control subjects had depleted their alactacid energy (12.2 +/- 3.3 Kcal). Only minor differences were observed in aerobic energy expenditure between the three subject groups throughout the sprint to exhaustion.

Adult↗