Anticoagulant control and standardization of coagulation reagents.
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Biomedical subjects
Publications and source records attributed to L Poller.
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In a long-term study of women taking the combined oestrogen/progestogen oral contraceptives Ortho-Novin and Norinyl-1 the follow-up has been continued for three years and four years respectively.Acceleration of both "intrinsic" and "extrinsic" clotting tests and of specific factor VII and X assays, reported previously at the nine-month stage, persisted throughout the period of study. Acceleration of Chandler's tube platelet aggregation and hypercoagulable thrombelastographic patterns were recorded. There was, however, no evidence of a cumulative effect after the first nine months.
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A two-year follow-up study of progestogen-only contraception with chlormadinone acetate indicates no increase of the level of factors VII and X, as found after three cycles with all oestrogen-progestogen oral contraceptives. Clotting factors which were raised with combined preparations became normal after the sixth monthly cycle of progestogen and remained normal during the two-year period of study.From 12 months onwards significant changes in the thromboelastograph pattern were recorded, but not to the same extent as with combined preparations. At two years platelet aggregation was significantly accelerated with chlormadinone acetate but was not as rapid as with combined preparations.
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1. Platelet aggregation in the Chandler's tube has been found to be increased in a group of normal male and female volunteers who undertook strenuous physical exercise. This coincided with acceleration of the ;intrinsic' blood clotting system and a rise in fibrinogen. The rise in fibrinogen occurred despite increased fibrinolysis.2. The study confirms the sensitivity of the platelet aggregation system to changes in the ;intrinsic' clotting mechanism. Acceleration of this system in this study resulted from a physiological cause and produced accelerated aggregation in the coagulation-affected phase.
A study has been made to determine whether a reliable comparison can be made between the British Comparative Thromboplastin and Thrombotest using the nationally adopted standardization procedure. The method recommended appeared sufficiently satisfactory and statistically valid for the comparison between the British Comparative Thromboplastin and Thrombotest. The degree of diversion in the location of the ;best lines', which should have been in an identical position at each centre, suggests that the standardization procedure at individual hospitals with Thrombotest is not usually a sufficiently reliable basis for clinical anticoagulant dosage. The degree of diversion almost certainly arises from technical error in the standardization procedure, and it is suggested that Thrombotest should be calibrated against the British Comparative Thromboplastin only in specialist coagulation centres thoroughly conversant with both techniques.
A severe, pure deficiency of factor VII has been defined in haematological and biochemical terms in the Alderley Park colony of beagle dogs. By modification of the conventional factor VII assay to improve its specificity an apparent low activity of between 1 and 2.5% of the normal beagle has been found. When this plasma is used as a substrate for factor VII assays it compares well with human factor VII-deficient plasma in the measurement of both raised and depressed factor VII activity. It also appears to be a valuable reagent in the quality control of tissue thromboplastin extracts.
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The national system for anticoagulant control depends on drawing the best line obtained by visual comparison of the points representing corresponding prothrombin ratios with the British comparative thromboplastin in the local reagent. This line is then used to correct subsequent values using the local laboratory method of corresponding values in terms of the British comparative thromboplastin.A study has been made of the statistical validity of the recommended system for anticoagulant control using the Quick one-stage test by comparing the line drawn by inspection with the confidence limits of the regression line. There was little difference between the best straight line by visual comparison and the calculated line for the majority of hospitals. The recommended procedure, therefore, provides an adequate conversion of the local method to the British comparative thromboplastin without the need for calculation. The significance of aberrant points is discussed and it is suggested that when more than two of the 12 results fall in this category the standardization procedure should be repeated.
Platelet aggregation has been found to be significantly accelerated with the coagulation-induced Chandler's tube technique in women taking combined oestrogen-progestin oral contraceptives, though this was less than in the third trimester of pregnancy. Women taking the pure progestogen, chlormadinone acetate, have not shown this change up to the sixth month of study. In contrast the accelerated platelet aggregation resulting from conventional oral contraception became normal one month after changing to the progestogen. There was no change in the platelet aggregation response to adenosine diphosphate (A.D.P.) during oral contraception.
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Platelet aggregation has been related to blood coagulation studies in patients on nicoumalone, a coumarin anticoagulant. Aggregation studies were performed by means of Chandler's tube and the adenosine diphosphate (A.D.P.)-induced optical density method. Platelet aggregation in Chandler's tube has been shown to be quite different from A.D.P. aggregation and to be dependent on the "intrinsic" (blood) clotting system. When the intrinsic system was depressed by coumarin anticoagulant, aggregation was delayed in Chandler's tube, but patients with a predominantly "extrinsic" (tissue) system defect gave normal results even when their prothrombin time was excessively prolonged. In contrast there was an increased response to A.D.P. in the anticoagulated patients.The study emphasizes the different mechanisms of platelet aggregation, which we have referred to as coagulation-induced and A.D.P.-induced aggregation. It also shows the limitations of routine control of oral anticoagulants by prothrombin time alone, as the coagulation-induced platelet aggregation appears to be quantitatively related to the overall level of clotting factors in the intrinsic system and independent of the extrinsic system.