ISSN:1424-8832    

DOI:10.1159/000216254

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000216255

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Leeching is an art dating back at least to ancient Egypt. It reached its zenith in the late 18th and early 19th centuries. The antithrombotic quality of leech saliva was first noted by Haycraft in 1884 and the active anticoagulant ingredient isolated in 1904 by Jacoby. He gave this agent the name ‘hirudin’. Hirudin was isolated in pure crystalline form by Markwardt in 1957 and first produced in quantity by genetic engineering in 1986. The salivary glands of several species of leech also contain other biologically active substances which are currently undergoing investigat

ISSN:1424-8832    

DOI:10.1159/000216256

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Three patients with ulcerative colitis in the active stage demonstrated reduced levels of F XIII activity and F XIII subunit A (61 and 80.3%, respectively). Because of the lack of clinical improvement during conservative therapy, the patients were treated additionally with F XIII concentrate (Fibrogammin HS®, Behring, FRG) for 10 days. The substitution resulted in an increase in F XIII activity (144.3%) and F XIII subunit A (238%) as well as in a marked improvement in symptoms

ISSN:1424-8832    

DOI:10.1159/000216195

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The kinetics of the activation of the plasmatic clotting system in the presence of heparin and depolymerized heparin (Kabi 2165), respectively, was compared with the kinetics of activation in plasma with isolated factor deficiency. Measurements were made with a chromogenic substrate method using Tos-Gly-Pro-Arg-p-nitroanilide acetate. The extinction curves were analyzed to determine the characteristics of a curve that was fitted to the experimental data to sufficiently describe the slope of the curves by constants. In the activated extrinsic clotting system, the action of heparin and depolymerized heparin results in a distribution pattern for the two relevant constants, K(l), defining the time of the point of inflection of the curve, and K(2), relating to the slope of the curve at the point of inflection, which is identical with the pattern observed in plasma with factor II deficiency. This distribution pattern can be explained by an inhibitory reaction on factor Ila, which is accelerated by the anticoagulant. In contrast, the pattern of K(2)/K(l) for the activated intrinsic system is identical with the pattern for plasma with factor X deficiency. Qualitative differences in the action of heparin and depolymerized heparin are not evident. The investigation confirms that the molecular action of heparin and depolymerized heparin as accelerators of the plasmatic clotting system is qualitatively the same. However, their action in the extrinsic and intrinsic system has different effects. Furthermore, the study reveals that constant K(2) is a more sensitive indicator to measure low heparin and depolymerized heparin activities than K(l) or its equivalent, the clotting time.

ISSN:1424-8832    

DOI:10.1159/000216196

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The naturally occurring anticoagulant from medicinal leeches, hirudin, which we isolated and biochemically analyzed 30 years ago as a miniprotein with specific anti-thrombin activity, has afterwards been employed for scientific and diagnostic purposes in hematology. Pure hirudin proved to be an antithrombotic agent of high quality that displays an antithrombotic action dependent upon its blood level. After intravenous injection, it is distributed in the extracellular space and is almost completely eliminated through the kidneys by glomerular filtration in a biologically active form. The efficacy of hirudin in preventing venous and arterial thrombosis and disseminated intravascular coagulation was demonstrated in various animal models. Clinical pharmacological studies corroborated the specific pharmacodynamic and pharmacokinetic properties of hirudin found in animal experiments. Genetic engineering led to the availability of sufficient quantities of recombinant hirudin (r-hirudin) for clinical purposes. Pharmacologic profiling of r-hirudin showed that both its pharmacokinetic and pharmacodynamic characteristics are very similar to those of native hirudin. Clinical pharmacological studies with r-hirudin revealed that, at single therapeutically relevant doses, r-hirudin is a well-tolerated and potent anticoagulant without any detectable side effects and allergic reactions. Further preclinical studies of r-hirudin should concentrate on identifying possible indications for use, on the development of r-hirudin preparations and derivatives, and on the development of antidotes for hirudin.

ISSN:1424-8832    

DOI:10.1159/000216258

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The levels of anticardiolipin antibodies (ACA) and lupus anticoagulant (LAC) were measured in 266 consecutive unselected patients with a history of venous thrombosis. 19 (7.1 %) had elevated levels of IgG- or IgM-ACA. The prevalence of LAC was 1 of 266 (0.4%) in the whole patient group and 1 of 19 (5.3%) in the ACA-positive group. Patients with elevated ACA levels did not differ from those with normal ACA with regard to age at the first thrombosis, risk of recurrence, presence of arterial thrombosis, and other clinical features. 8 out of 19 (42.1%) patients with elevated ACA levels also had elevated levels of antinuclear antibodies, but only 1 fulfilled the criteria of systemic lupus erythematosus. These data indicate that in some patients with elevated ACA, autoimmune processes may be present. The clinical significance of elevated ACA levels is uncertain.

ISSN:1424-8832    

DOI:10.1159/000216197

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Separation of lupus anticoagulant from anticardiolipin antibodies in the serum of a patient containing both antibodies is described. A simple two-step procedure utilizing diethylaminoethylcellulose ion-exchange chromatography followed by Sepharose CL-4B gel filtration chromatography allowed the separation of IgM from IgG isotype. Lupus anticoagulant was found to be exclusively IgM, whilst anticardiolipin antibodies were IgG. This is apparently the first report that anticardiolipin antibodies and lupus anticoagulant can be different isotypes and adds to the increasing evidence that they are separate entities.

ISSN:1424-8832    

DOI:10.1159/000216198

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

In addition to its classical active-site regions (catalytic site and adjacent regions), α-thrombin has a unique anion-binding exosite, which is functionally independent of the catalytic site and is involved in fibrin(ogen) recognition. This exosite also accounts for adhesion to negatively charged surfaces (e.g., glass), binding to cell surfaces, and interactions with the anionic tail of hirudin. Hirudin (as an apolar, tridisulfide-linked core structure followed by its anionic tail) interacts with α-thrombin by apolar (e.g., catalytic-site and adjacent regions of thrombin), as well as by ionic binding (e.g., anion-binding exosite). Circular dichroism measurements reveal a sigmoidal nonadditivity for the hirudin tail fragments, which block fibrinogen-clotting activity without interfering with tripeptide chromogenic substrate activities. Such fragments, however, inhibit factor V activation to much lesser extents than hirudin, where factor V activation is the key step in regulating thrombin generation by hirudin or heparin/antithrombin III. Hirudin-derived antithrombotics may thus have differential modes of action in hemostasis and wound healing processe

ISSN:1424-8832    

DOI:10.1159/000216259

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The effects on primary haemostasis of unfractionated heparin and of the two low molecular weight heparins, enoxaparin and fragmin, were compared in two rat models, one employing the gastric mucosa and the other the tail skin. All three heparin preparations prolonged the bleeding time and increased the blood loss dose dependently. The prolongation of the bleeding time per unit dose caused by unfractionated heparin was significantly greater than the prolongation caused by either one of the two low molecular weight heparins. In the gastric mucosa, but not in the tail skin, enoxaparin prolonged the bleeding time significantly less than fragmin (p < 0.05).

ISSN:1424-8832    

DOI:10.1159/000216199

出版商:S. Karger AG    

年代:1991

数据来源: Karger