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Biomedical subjects

L Poller

Publications and source records attributed to L Poller.

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

The cause of turbidity in lyophilised plasmas and its effects on coagulation tests.

AIMS: To investigate the cause of turbidity in reconstituted lyophilised plasmas and to determine its effect on coagulometers. METHODS: The turbidities of 20 normal plasmas and 16 reconstituted lyophilised plasmas were determined by comparing a 1 in 4 dilution in distilled water with a standard suspension in an Aminco Fluorocolorimeter (American Instrument Co) in nephelometric mode. The turbidities of five other plasmas were determined before and after lyophilisation. The turbid components of fresh and reconstituted lyophilised plasmas were studied using electron microscopy. The effects of turbidity on five types of coagulometer were determined by adding varying concentrations of a turbidity enhancing material. RESULTS: Reconstituted lyophilised plasmas were more turbid than normal plasmas, because of agglomerated liposomes. Serum depleted of chylomicrons and very low density lipoproteins was not rendered more turbid by lyophilisation. Three out of five types of automated coagulometer tested gave activated partial thromboplastin times which were appreciably affected by plasma turbidity. One of the instruments was unable to detect a clot in a moderately turbid plasma. A second instrument gave results which were significantly affected by turbidity. Turbidity of the substrate plasma did not affect specific factor VIII assays in two types of coagulometer. CONCLUSIONS: Lyophilisation of plasma induces turbidity due to the agglomeration of lipids. Such turbidity can affect the results of coagulation tests. Suppliers of lyophilised plasmas should be aware of this problem.

Blood Coagulation Tests

Survey of oral anticoagulant treatment in children.

AIMS: To find out which children are treated with oral anticoagulants and how their treatment is controlled in the United Kingdom. METHODS: Two questionnaires were used. The first was sent to general haematologists and the other to paediatric cardiologists and cardiac surgeons. RESULTS: There were 273 (58%) replies to the first questionnaire. Most children were treated because of artificial cardiac valve replacement. The mean target International Normalised Ratio (INR) used was 2.73 to 4.0 for children with heart valves and 2.1 to 3.25 for children with venous thrombosis. The second questionnaire elicited replies from 11 of 22 cardiac centres. The mean target INR used for children with cardiac valves ranged from 2.59-3.77. Of 68 children covered in the survey, there have been two major bleeds and two thrombotic episodes: 78.8% of children were controlled with a venous prothrombin time and 21.2% with a capillary test. There was no consistency in the dose regimens used for the induction of oral anticoagulant treatment with warfarin. CONCLUSIONS: The levels of anticoagulation used for maintenance are similar to those recommended by the British Society for Haematology for adults (3.0 to 4.5). They seem to be safe for children too.

Administration, Oral

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

A study of impaired fibrin polymerization in patients with the nephrotic syndrome.

Clotting studies have been performed on 64 consecutive patients with nephrotic syndrome. The thrombin time was prolonged in 59. Fibrin polymerization was studied in 42 of the 59 patients with a prolonged thrombin time and an abnormality was present in 22. There was a significant correlation between the prolongation of the thrombin time and impairment of polymerization (p = 0.018). No correlation was found between these two parameters and the patient's sex, age and drug therapy. Furthermore there was no correlation with the prothrombin time, APTT, fibrinogen, FDP, antithrombin III and platelet counts. There was however a significant negative correlation between the thrombin time and the serum albumin level (p less than 0.05). No abnormal bleeding was observed during or after renal biopsy in these patients. Renal biopsy may be performed safely despite the grossly prolonged thrombin time and abnormal fibrin polymerization in patients with the nephrotic syndrome.

Adult

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

Special report: a simple system for the derivation of International Normalized Ratios for the reporting of prothrombin time results with North American thromboplastin reagents.

The World Health Organization international scale of reporting prothrombin time results is based on the calibration of thromboplastins against an international reference preparation to derive an International Sensitivity Index (ISI). Once the ISI has been assigned to an individual thromboplastin reagent, the derivation of International Normalised Ratios (INRs) for reporting results depends on mathematic formulae requiring a special calculator or mathematic tables. This causes difficulties and errors. A simplified system for interpretation of INRs with the range of thromboplastins widely used in North America is therefore presented, which obviates the need for mathematic procedures for the derivation of INR equivalents. It should thus facilitate the application of the INR system and of safer therapeutic ranges.

Calibration

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