Quality control of coagulation tests in different countries. An introduction.
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Biomedical subjects
Publications and source records attributed to L Poller.
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In monitoring the effects of industrial exposure resulting from the pharmaceutical manufacture of oestrogen-progestogen combinations by coagulation studies acceleration of some clotting tests was found. The most pronounced changes were in workers most closely associated with the industrial process. Less pronounced changes were found in women employees not closely concerned with the processing and may have been secondary to the postmenopausal bleeding to which they were prone. A safer work procedure elaborated by the Employment Medical Advisory Service was monitored by clotting studies for over a year but the three most highly exposed subjects showed no substantial improvement.
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A series of collaborative exercises on the one-stage prothrombin time test involving hospitals in Britain and overseas was performed between 1972 and 1977. The British Comparative Thromboplastin (BCT) and the lyophilised test plasmas were issued from the National (UK) Reference Laboratory for Anticoagulant Reagents and Control. Participants were asked to test the plasma samples with the BCT using the recommended technique. Variability of performance was assessed by the 'index of reliability' based on the plasma variance and error variance within each exercise. The results show that hospitals have attained higher precision in the later trials.
In 33 patients, a significant fall in the fibrinogen level occurred during an operation to replace the abdominal aorta by a bifurcated prosthesis. There was a similar, but less marked, fall in the fibrinogen level of ten patients having a femoropopliteal vein bypass. A concomitant drop in the plasma plasminogen value was also found. Results of specific laboratory tests for intravascular clotting and activation of fibrinolysis were negative. This suggests that fibrinogen may be removed by physical means. The fall in fibrinogen was so low in some patients that the routine administration of a conventional dosage of heparin could be dangerous.
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The British comparative thromboplastin (BCT) was used to monitor the effectiveness of oral anticoagulants in preventing deep vein thrombosis (DVT) in patients undergoing major gynaecological surgery. All patients were screened for DVT with the use of the (125)I-fibrinogen scan.One hundred and forty-five patients aged 40 years or more were randomised into three groups. Group 1 received oral anticoagulant (nicoumalone) treatment, stabilised over five days before surgery and continuing into the second postoperative week. The other patients served as two contrast groups and were managed on a double-blind basis. Group 2 received a subcutaneous low-dose regimen of heparin calcium. Group 3 received subcutaneous saline. Eleven of 48 patients in the saline group, three of 49 patients in the heparin group, and three of 48 patients in the oral anticoagulant group developed DVT as judged by (125)I-fibrinogen scanning. The incidences in groups 1 and 2 were significantly lower than in the saline group. The falls in haemoglobin concentration and incidence of haemorrhage were similar in all three groups.The study showed that oral anticoagulant prophylaxis stabilised preoperatively and low-dose heparin were equally effective in preventing deep vein thrombosis in a moderate-risk group. Immediate preoperative prothrombin ratios of 2.0-2.5 and postoperative ratios of 2.0-4.0 with the BCT gave adequate protection without increased haemorrhagic risk.
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An international framework for anticoagulant control has been developed based on British Comparative Thomboplastin (B.C.T.) and the model provided by the British system for anticoagulant control. An alternative international system has been proposed, based on lymphilised thromboplastins prepared at the National Institute of Biological Standards and Control, London. Since 1969, stability studies on two of the N.I.B.S.& C. reagents, the primary material 67/40 and the secondary thromboplastin 69/223, have been in progress at the National (U.K.) Reference Laboratory for Anticoagulant Reagents and Control, Manchester. Both the proposed N.I.B.S.&C. reference preparations have deteriorated, while two lyophilised reagents prepared at the National (U.K.) Reference Laboratory have revealed no evidence of instability. In national and international standardisation reliance on B.C.T. should continue.
A follow-up study of blood clotting and platelet aggregation was performed on 21 women who had received long-term hormone replacement treatment with conjugated equine oestrogens. The prothrombin time and factor VII and X values were significantly accelerated after three months, but there was no further increase with continual administration for 18 months. After 12 to 18 months' treatment, however, thrombin-induced platelet aggregation (Chandler's tube) was also significantly accelerated, which suggested a widening spectrum of effect. No overall acceleration of "intrinsic" clotting (partial thromboplastin time and thromboelastography) was found during the study, but the relatively small numbers may have been responsible. Further efforts are therefore required to find formulations and doses of oestrogens which, while relieving menopausal symptoms, cause less acceleration of blood clotting and platelet aggregation.
The frequent occurrence of abnormal fibrin polymerisation in patients with liver disease has recently been reported. To investigate this further, fibrin polymerisation was studied in 68 patients with cirrhosis or chronic active liver disease. Thirty-three of these patients demonstrated impairment of this phase of blood coagulation. When other tests of liver function were compared in patients demonstrating this abnormality and those in whom fibrin polymerisation was normal, it was found that the former group demonstrated significantly reduced albumin concentrations (p less than 0.0002), raised bilirubin and aspartate aminotransferase levels (p less than 0.0006 and less than 0.003 respectively), and greater prolongation of the one-stage prothrombin time (p less than 0.001) with more marked reduction in factor VII levels (p less than 0.002) compared with the latter patients. It is concluded that defective fibrin polymerisation occurring in patients with liver disease indicates the presence of severely impaired hepatocellular function. This might account for the grave prognosis reported in cirrhotic patients with abnormal fibrin polymerisation who also suffer bleeding from gastro-oesophageal varices.