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Biomedical subjects

K W Denson

Publications and source records attributed to K W Denson.

At least 37 records · Page 2Linked to original sources
PubMed1988

Thromboplastin--sensitivity, precision and other characteristics.

A more sensitive or higher concentration of rabbit brain thromboplastin does not result in greater accuracy and precision of results in oral anticoagulant therapy and is unable to mimic the PIVKA sensitivity of human brain. In terms of International Normalized Ratios the British Comparative Thromboplastin and Manchester Comparative Reagent (both now discontinued) and the Manchester Reagent had the poorest sensitivity to factor VII of all the reagents studied. It is not possible accurately to calibrate rabbit brain against human brain thromboplastin in the upper therapeutic range and beyond.

Animals↗
PubMed1987

Production of factor VIII deficient plasma by immunodepletion using three monoclonal antibodies.

Factor VIII deficient plasma was made from pooled, HIV antibody and hepatitis B antigen screened, normal human plasma by cryoprecipitation and immuno-depletion, using three different monoclonal antibodies bound to Sepharose columns, in series. These monoclonal antibodies are specific respectively for von Willebrand factor, factor VIII heavy chain and factor VIII light chain. The immunodepleted plasma contained less than 0.002 u/ml factor VIII coagulation activity (VIII:C) less than 0.0001 u/ml von Willebrand factor antigen and 1-2 g/l fibrinogen, while the levels of other clotting factors were unchanged. This immunodepleted plasma was compared with commercial factor VIII deficient plasma obtained from a severe haemophilia A patient as substrate in the one-stage factor VIII assay. Plasmas obtained from 20 normal subjects and 28 patients with von Willebrand's disease or haemophilia A were assayed for VIII:C using the two substrates. The results were very highly correlated (r = 0.96). The columns have high capacity and can be regenerated at least 10 times. Large-scale production of a substrate for factor VIII assays free of virus contamination is now feasible.

Antibodies, Monoclonal↗
PubMed1982

Congenital factor VII deficiency. Clinical and laboratory characteristics of a newly discovered kindred.

Four generations of a newly discovered kindred suffering from congenital factor VII deficiency have been studied. The abnormality was transmitted as an autosomal recessive character and resulted in homozygotes with less than 1% factor VII procoagulant activity. Antibody neutralization tests using a monospecific rabbit anti-human factor VII antibody demonstrated the presence of factor VII antigen in excess of factor VII procoagulant activity. The disorder has therefore resulted from the presence of a functionally abnormal factor VII molecule and not from a true deficiency of this factor. When the plasmas from the homozygotes were tested in the prothrombin time test using human, rabbit and ox tissue thromboplastins, a progressive diminution in the ability of these reagents to detect the factor VII procoagulant deficiency was observed. These differences were however small and the complete insensitivity of ox brain thromboplastins that characterizes the factor VII Padua abnormality was not observed.

Adolescent↗
PubMed1980

Thromboplastin reference preparations.

The need for standardization of methods for the control of anticoagulant therapy was apparent 25 years ago. With the development of the ratio method for comparing the sensitivity of different thromboplastin preparations it became possible to equate the value obtained with one preparation in terms of the value which would be obtained with any other preparation, and the need for a reference to serve as a yardstick for comparison became obvious. The first trial reference preparation was developed in 1965 and three small international trials on the calibration of different thromboplastin preparations were conducted. The first international reference preparation was laid down in 1967 coded 67/40, and other preparations containing ox brain, human brain and rabbit brain and coded 68/434, 69/223 and 70/178 followed. Further collaborative studies were carried out in 1970 and 1973, and a large international trial undertaken in 1974, using 70/178 as the reference preparation. These preparations have remained stable over a period of 9 to 12 years and their usefulness for purposes of calibration and international trials has been proven. Three further reference preparations were laid down in 1979 and a further international collaborative study has been undertaken.

Animals↗
PubMed1977

Factor-VIII consumption in pre-eclampsia.

In 50 women with high-risk pregnancies, increased factor-VII consumption, as estimated by the difference between the levels of factor-VIII-related antigen and factor-VIII clotting activity, correlated with the severity of pre-eclampsia, particularly when measured by increases in plasma-urate. Longitudinal studies of the evolution of pre-eclampsia demonstrated that increased factor-VIII consumption usually but not always developed before hyperuricaemia. The earliest time that abnormal factor-VIII consumption was demonstrated was at 18 weeks' gestation in a woman who had had two previous stillbirths. Subcutaneous heparin and oral dipyridamole failed to reverse the coagulation abnormality, and the fetus died in utero at 28 weeks' gestation. The renal and coagulation changes characteristic of pre-eclampsia were also seen in a patient without hypertension. This suggests that the concept of pre-eclampsia may need to be widened to include a non-hypertensive syndrome characterised by these changes in clotting and renal function.

Adult↗
PubMed1977

Factor-VIII activity and antigen, platelet count and biochemical changes after adrenoceptor stimulation.

Adrenaline, isoprenaline and salbutamol were administered by intravenous infusion to human subjects. Isoprenaline was covered with practolol in an attempt to reduce the unpleasantness of the circulatory effects. Changes were recorded in pulse rate and blood pressure, and in blood levels of factors V, VIII, X, XI, and XII, platelet count, lactate, pyruvate, potassium and free fatty acids. Factor VIII was studied by clotting assays, by reactions with two rabbit antisera and two human antibodies, and by desulphated agarose chromatography. At the rate at which they were adiminstered, all three drugs increased the pulse rate by 20-40 beats/min. Factor VIII rose c. 2.5 X with adrenaline but only c. 1.5 X with isoprenaline and salbutamol; but other clotting factors did not alter. Chromatography provided no evidence of a change in the size of the molecule carrying factor-VIII clotting activity. The rate of clearance of the heightened plasma activity could not be shown to differ from that of "ordinary" factor VIII infused into haemophiliacs. The platelet count rose after adrenaline, fell after salbutamol and did not change significantly after isoprenaline. Among the biochemical responses, the only significant difference between the drugs was that lactate rose after adrenaline and salbutamol but did not change after isoprenaline. The rise in factor-VIII clotting activity after adrenaline is considered to represent a real increase in blood concentration, presumably by release of additional factor VIII from stores. The evidence suggests that this could be classified as a beta2 effect; and that the quantity which can be released is unrelated to the current plasma level. The rise in platelet count produced by adrenaline may be the resultant of an alpha-mediated rise due to contraction of the exchangeable splenic pool and a beta2-mediated fall, the alpha effect predominating.

Adult↗
PubMed1976

The clotting of a snake (Crotalus viridis Helleri) plasma and its interaction with various snake venoms.

The clotting of C. V. Helleri plasma is not accelerated by the factor X activator or thrombin-like enzymes from its own venom. Clotting of the plasma is accelerated by the factor Xactivator from Russell's viper venom, but not by the thrombin-like enzyme from Agkistrodon Rhodostoma venom ("Arvin"). The prothrombin activator from the Taipan venom clots C.V. Helleri plasma equally well as human plasma, but the thrombin which is produced has a marked specificity for its own fibrinogen, and clots bovine fibrinogen more slowly. C.V. Helleri plasma contains an inhibitor which progressively inactivates bovine factor Xa and thrombin, but the inhibitor is not potentiated by heparin. The slow, protracted clotting of the snake plasma either alone or when mixed with human plasma or bovine fibrinogen suggests that this inhibitor may interfere with the polymerisation of fibrin monomer.

Ancrod↗
PubMed1976

The role of coagulation and fibrinolysis in preeclampsia.

The coagulation and fibrinolytic systems play a key role in maintaining the integrity and patency of the vascular compartment. Pregnancy induces extensive physiological changes in these systems, thus creating an enhanced capacity to produce fibrin and a diminished ability to remove it. Fibrin deposition localized to the uteroplacental circulation is a feature of normal pregnancy. In women with fatal eclampsia, disseminated intravascular coagulation with fibrin deposition in the renal glomeruli is well documented. The condition of preeclampsia is not well defined. Nonetheless, evidence of intravascular coagulation, as shown by elevated levels of fibrin degradation products and reduced platelet counts, has been found in many women with preeclampsia. Serial studies showed that thrombin generation, as indicated by the ratio of factor VIII-related antigen to factor VIII coagulant activity, is considerably in excess of that which occurs in normal pregnancy, and its appearance coincides with the development of the clinical features of preeclampsia. Heparin therapy has bot been proven of value in established preeclampsia, but this fact does not disprove that role that intravascular coagulation may play in the pathogenesis of the disease. A controlled trial ina high-risk group of low-dose he;arin and an antiplatelet agent from the 16th to the 18th weeks of pregnancy onwards is required to elucidate the role of intravascular coagulation in preeclapmsia and its effect on the fetus.

Blood Cell Count↗
PubMed1975

Measurement of heparin in patients receiving subcutaneous heparin therapy.

Heparin assays based on four different tests of clotting function have been compared with a heparin assay utilizing the potentiating effect of heparin on anti-factor Xa in a group of patients receiving subcutaneous heparin therapy during late pregnancy. It is considered that the anti-factor Xa method is a better indication of the antithrombotic effect of heparin. In the presence of high levels of clotting factors, heparin assays based on tests of clotting function can be misleading.

Blood Coagulation Tests↗