[Chromogenic substrates. Their diagnostic use in blood coagulation and fibrinolysis].
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Biomedical subjects
Publications and source records attributed to F Duckert.
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Specific antibodies against human factor VIII have been prepared in rabbits and ducks. These antibodies differ from each other in that duck anti VIII antibody precipitates human and rabbit factor VIII, whereas rabbit antibody does not precipitate its own factor VIII. It is possible that the two antisera detect carriers differently.
At III levels measured with six methods in 36 people: 10 healthy controls, 10 women taking a progestagen Lynestrenol and 16 women taking a combined oestrogen-progestagen contraceptive pill. The reproducibility and the sensitivity of these methods as well as the correlation between methods were studied. The Hensen and Loeliger technique had a poor reproducibility and the results obtained with the Howie technique were not in good correlation with those obtained with other methods, especially in the group taking oral contraceptives. The two amidolytic methods using chromogenic substrates were found to be very accurate for antithrombin III activity determination. The rocket immunoelectrophoresis was more accurate and more practical than the radial immunodiffusion. With all methods--except the one of Howie--the 10 women taking progestagen Lynestrenol and the 16 taking combined oestrogen-progestagen had a low AT III and differed significantly from the 10 normals tested. No difference was observed between women taking progestagen only or an oestrogen-progestagen combination.
20 coagulation parameters were investigated in 144 patients with different liver diseases. The groups of acute hepatitis, chronic active hepatitis and liver cirrhosis were compared and the prognostic value of the coagulation analyses investigated. It is clear that the determination of the factor V activity is a good and easy test for detection of actual liver function. Repeated controls over several weeks revealed with a statistical significance (p less than 0.0005) that all patients with a factor XIII below 35% and a plasminogen below 19% will die in liver coma, if they have not died beforehand from acute gastrointestinal haemorrhage, acute infection or cardiac arrest. Plasminogen is also lower in the group of non-survivors but the values of the two groups are overlapping and of no prognostic help in a single case. The possible causes of the diminution of factor XIII activity are discussed.
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The proteolytic enzymes of the coagulation and fibrinolysis systems as well as others such as kallikrein, activated under pathological conditions can be determined directly, without manipulations of the plasmas, with the synthetic chromogenic substrates. With these substrates it is possible to follow the protease activity in disseminated intravascular coagulation, during thrombolysis and under other conditions. The lack of absolute substrate specificity makes it imposssible to identify the activated proteases.
It has been demonstrated that activated factor XIII may catalyze the formation of covalent cross-links between fibrin and collagen. This is shown by the disappearance of the gamma-gamma dimer band in PAA-SDS gel electrophoresis when fibrinogen is clotted in presence of collagen, factor XIII and Ca ions, and by the binding of labeled fibrinogen. This reaction may explain the outstanding physiological importance of factor XIII.
Experience with different peptide substrates for coagulation and fibrinolysis is reported. As the specifity of these substrates is relative, appropriate characterization of the proteolytic activity of defibrination syndromes is only achieved by simultaneous assays with various substrates. The influence of contact activation on blood sampling must be strictly defined.
Evaluation of the therapeutic range of oral anticoagulation for different commercial thromboplastins in comparison with Quick's human brain thromboplastin and Thrombotest is based on simultaneous performance of all methods for each blood sample, on strict adherence to the manufacturer's instructions and on adequate statistical analysis.
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The snake venom enzymes Ancrod and Batroxobin marajoensis are able to activate human plasma factor XIII as shown by the formation of the gamma-dimers. The concentration of gamma-dimers increases with the concentration of the activating enzymes. Factor XIII activated by Ancrod or Batroxobin marajoensis is, however, unable to catalyse the incorporation of the amine dansyl-cadaverine into casein. The partially activated factor XIII is therefore not demonstrable by means of the artificial test system. This factor XIII loses little activity and remains activable by thrombin.
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The efficacy of dextran-40 infusions or low-dose heparin or xantinol-nicotinate administration in preventing postoperative thromboembolic complications has been investigated in a prospective, controlled, randomised trial as part of an international multicentre trial. 382 patients over the age of forty years undergoing elective major general surgery were investigated; 100 had a complete protocol in the control, 94 in the heparin, 92 in the dextran, and 32 in the xantinol-nicotinate group. 31 patients died: 13 in the control group, 10 in the heparin group, 6 in the dextran group, and 2 in the xantinol-nicotinate group. In 4 controls, 6 in the heparin group, and 1 in the dextran group the cause of death was acute pulmonary embolism. 4 further controls, 1 in the heparin group, and 2 in the dextran group had emboli found at necropsy, which either contributed to the deaths or were incidental findings. The distribution of pulmonary emboli in this study did not show the difference between the control and the heparin group reported in the multicentre trial. The 125I-fibrinogen test was done in all patients. The frequency of isotopic deep-vein thrombosis was 36-0% in the controls, 12-8% in the heparin group, 21-7% in the dextran group, and 40-6% in the xantinol-nicotinate group. The difference between the controls and the heparin groups was highly significant and between the control and the dextran group, probably significant. There were significantly more side-effects in the heparin group than in the dextran group.
The effects of flurbiprofen on various coagulation and haemostasis parameters were studied in 19 patients adequately anticoagulated on a fixed dose of phenprocoumon. Laboratory controls were performed 5 times at weekly intervals. Flurbiprofen 50 mg 3-times daily was given for 2 weeks after an initial control period of 2 weeks. The last control followed 1 week after cessation of flurbiprofen. All changes observed during the administration of flurbiprofen were quantitatively moderate; some reached statistical significance. The prothrombin time (%) Factor II and Factor X values fell; Factor II values remained unchanged. Factor IX values fell only in the first week on flurbiprofen and reached control values thereafter. Phenprocoumon concentration remained constant throughout. There was no change in spontaneous platelet aggregation. Although there was a slight, statistically significant increase in the Ivy bleeding time, it remained within the normal range. These findings suggest that the interference of flurbiprofen with oral anticoagulation is minimal and probably of no clinical relevance.