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Biomedical subjects

D A Taberner

Publications and source records attributed to D A Taberner.

At least 37 records · Page 2Linked to original sources

Safety of anticoagulation in the elderly: reasons for discontinuing therapy.

We have conducted a retrospective study on the reasons for discontinuing anticoagulants in 50 patients over the age of 75 years compared with 198 adults under 75 years to determine the safety of therapy in the elderly. Venous thromboembolism and arterial embolization were the most common indications for therapy in the elderly and the median duration of therapy in all patients was 7 months (9 days-22 years). There were no deaths attributable to anticoagulants. There was no significant difference in the proportion of elderly patients who stopped treatment because of bleeding compared with 198 patients under 75 years (5/50 (10%) vs 12/198 (6.1%), P = 0.26), nor in the rate of bleeding between the two groups (5/52.5 (9.5%) treatment-years vs 12/249 (4.8%) treatment-years, P = 0.15). This complication rate does not suggest that age per se is a risk factor in the use of oral anticoagulants.

Age Factors↗

Comparison of test methods for the lupus anticoagulant: international survey on lupus anticoagulants-I (ISLA-1).

Six lyophilized plasma samples were sent to 20 "expert" laboratories for assessment of lupus anticoagulant (LA). Four samples contained pooled LA of graded potency mixed with aged normal plasma. One contained LA plus cephalin phospholipid and one contained a nonspecific venom anticoagulant. Sixteen methods were used overall with some participants using up to 8 methods. Results were scored in regard to the known potencies of LA in the samples and other known induced defects. Activated partial thromboplastin time (APTT) tests used by most participants for preliminary screening were relatively sensitive, but non-specific. Platelet or phospholipid neutralization procedures (PNP) appeared to be sensitive and specific but showed a non-linear response to increased LA content. Kaolin clotting time (KCT) tests showed the most sensitive response to increased LA content but the weaker LA were not scored as abnormal by most laboratories as the samples may have contained platelet fragments. Other commonly used tests such as the tissue thromboplastin inhibition (TTI) test and the dilute Russell's viper venom test (DRVVT) were carried out somewhat inconsistently. The variability in performance of tests in different laboratories indicates that standardization of methodology is urgently required. Generally it seemed that most clotting tests were "bypassed" by the addition of phospholipid to a known LA-positive sample in apparently direct proportion to their sensitivity. Sample preparation, especially prevention of contamination with activated platelets is a vital preliminary part in the assay of LA.

Autoantibodies↗

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↗

Type I protein S deficiency and skin necrosis.

A kindred with Type I protein S deficiency is described in which the index case developed skin necrosis during induction of oral anticoagulant therapy for deep venous thrombosis. Two other family members with protein S deficiency have been detected, and demonstrate the clinical variability of this condition.

Acenocoumarol↗

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↗

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↗

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↗

An evaluation of APTT monitoring of low-dose heparin dosage in hip surgery.

The activated partial thromboplastin time has been used to monitor the effects of low-dose subcutaneous heparin in two groups of patients undergoing hip surgery. The study was performed to determine the degree of anticoagulation required to protect these high-risk patients from post-operative deep vein thrombosis. The patients were randomised to receive a fixed regimen of subcutaneous calcium heparin (5,000 units eight-hourly) or a dose of calcium heparin monitored by maintaining the standardised APTT at 50 secs. In the adjusted group the APTT achieved the target figure in 46% of observations compared to 27% in the fixed group (p less than 0.005). Nine patients showed positive 125I-fibrinogen scans and in all, the APTT was below the target value the day before the scan became positive. In contrast, in six of the nine thrombotic patients heparin was detected by antifactor Xa clotting assay. The APTT, therefore, appears to give a better guide to the antithrombotic effect of heparin than the antifactor Xa clotting assay. These preliminary observations suggest that prolonging the standardised APTT method to just above 50 secs improves prophylaxis in high-risk cases. Furthermore, an increased dose of heparin is required than is proved during the conventional low-dose regime of 5,000 units tds. With regular control using the standardised APTT, increasing the dose to the target value does not increase post-operative haemorrhage. Further studies with larger numbers of patients are required in order to show a significant reduction in the incidence of post-operative deep vein thrombosis in hip surgery patients receiving low-dose adjusted heparin.

Adult↗

Dosage and control of oral anticoagulants: an international collaborative survey.

An international survey of oral anticoagulant dosage has been carried out comparing the mean dosage prescribed in hospitals in 23 countries. In addition, participants using the Quick prothrombin time test were asked to assess the adequacy of dosage of a lyophilized test plasma which was mid-therapeutic using the British Comparative Thromboplastin (BCT). The overall mean dosage proved similar for the groups of laboratories using the Quick test and human brain thromboplastin and Thrombotest although wide differences existed between individual centres. The survey indicated that these discrepancies were due partly to the adoption of different intensities of anticoagulation. In addition, local differences in patients' response to anticoagulants were apparent, e.g. North American centres prescribed a higher mean dose with a more intense therapeutic range than Europeans. Hong Kong physicians appear to prescribe a much lower dose than the rest of the world although the intensity of their treatment is comparable, whereas South African hospitals give moderate doses of warfarin despite a conservative therapeutic range. Such geographical variation in response would invalidate standardization of anticoagulant treatment based on the mean dosage approach.

Administration, Oral↗