摘要:

Arterial and venous thromboembolic events represent frequent and life-threatening complications in homocystinuric patients and are responsible for their early deaths. Reduced levels of antithrombin III activity in homocystinuric patients have recently been reported. So, high plasma L-homocysteine concentration could play a role in the low antithrombin III activity level. In the present study, we have studied the relationship between total plasma homocysteine and inhibitors of blood coagulation levels in 16 patients with malignancies who received bone marrow grafts. There were no correlations between homocysteine values and inhibitors of blood coagulation levels. So, while the defect in amino acid transsulfuration that is responsible for homocystinuria can directly affect the synthesis or activity of some clotting factors, homocysteine concentration is not responsible for this effect.

ISSN:1424-8832    

DOI:10.1159/000216205

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

In this study we report the data obtained from extensive haemostatic testing of 25 patients undergoing orthotopic liver transplantation and the results of an open randomized pilot trial of antithrombin III concentrate administration during surgery. Marked differences in transfusional needs and in pre- and intraoperative blood coagulation and fibrinolytic changes were observed between recipients with liver cirrhosis and those with primary biliary cirrhosis. In the former, the increases in tissue-type plasminogen activator activity, total euglobulin fibrinolytic activity, and fibrin-derived degradation products occurred earlier and were more marked, as were the signs of increased thrombin formation. Supplementation of antithrombin III concentrate during surgery failed to induce significant changes in the main parameters studied and in the transfusional needs.

ISSN:1424-8832    

DOI:10.1159/000216206

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The ether phospholipid KO-286011, which is related to platelet-activating factor (PAF), was examined for PAF-antagonistic action on rabbit platelets both in vitro and ex vivo. It inhibited the aggregation of washed platelets induced by PAF (5 nmol/l) concentration dependently (IC50 = 6.5 × 10-7 mol/l). After injecting 0.5 mg/kg to rabbits, the ex vivo PAF-mediated aggregation in heparinized platelet-rich plasma was influenced selectively. The inhibition was short and maximal after 5 min. In contrast, hematocrit, counts of peripheral platelets and leukocytes, hemoglobin content, partial thromboplastin time, prothrombin time, and fibrinolytic activity in plasma were not affected. However, the therapeutic range of KO-286011 is limited because of membranolytic activity at higher dosages, leading to hemolysis and drop of circulating platelet counts

ISSN:1424-8832    

DOI:10.1159/000216207

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

The time-dependent release by human α-thrombin of the physiological variants of fibrinopeptide A, i.e. fibrinopeptide A-3-phosphate (FPAP) and des-Ala-fibrinopeptide A (FPAY), has been measured in order to study the kinetic pathway for their hydrolysis. The best-fit kinetic model for the release of FPAP and FPAY is consistent with a simple pseudo first-order reaction, as observed with FPA. These findings indicate that FPAP and FPAY are also released from intact fibrinogen before release of FPB. The values of the specificity constants, i.e. kat/Km, for the enzymatic reaction between thrombin and the various α-chains showed that APα- and AYα-chain are hydrolyzed with a 0.2-and 0.4-fold higher specificity constant respectively than that of Aα-chain. Such minor differences observed with the various chains suggest that the 1–3 NH2-terminal residues of the chain do not significantly contribute to the catalytic efficiency of thrombin toward the α-chains of fib

ISSN:1424-8832    

DOI:10.1159/000216208

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

In a randomized, blind study, both the antithrombotic efficacy (reduction of thrombus weight) and potency (anti-Xa activity) of several commercially available low-molecular-weight heparins (LMWHs) were compared with those of unfractioned heparin (UFH) and placebo. Three different thrombogenic challenges were used: venous thrombosis was induced by direct endothelial damage in 60 New Zealand rabbits (group I), intracarotid injection of bovine thrombin in an additional series of 60 rabbits (group II), or after inferior-vena-cava ligature in 60 Wistar rats (group III). The drugs were administered subcutaneously 2 h before surgery in a blind fashion. The doses recommended for clinical practice were used (adjusted by body weight), except in group II animals, in whom doses were doubled. No differences were found between UFH and most LMWHs in terms of reduction of thrombus weight in group I animals. But UFH showed a weaker antithrombotic efficacy in the other two models. Similarly, one of the LMWHs used (Clexane) proved to be not as effective as the remainder. However, only clinical studies will provide enough information to verify these differences. Additionally, our findings confirm that the antithrombotic efficacy of a given drug differs according to the stimulus used to induce venous thrombosis.

ISSN:1424-8832    

DOI:10.1159/000216209

出版商:S. Karger AG    

年代:1991

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000216210

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

In an attempt to elucidate the antithrombotic potential of defibrotide (D) we have evaluated several functions of monocytes from 7 healthy subjects before and after in vitro incubation of the cells with increasing concentrations of this drug. At concentrations as high as 40 μg/ml, D hardly affected the expression of both the procoagulant activity of monocytes and the formation of superoxide anion in response to 1 mg/ml zymosan (STZ). In contrast, at concentrations that may be achieved in vivo following the administration of the drug (5–20 μg/ml), D impaired in a dose-dependent manner (p < 0.05) the generation of O-2 in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP, 1 μM) or calcium ionophore A23187 (10 μM). Regardless of the agonist employed, at concentrations between 1 and 5 mM, extracellular Ca2+ 30%) being observed when the cells were preincubated with the drug for 20 h. These data support the concept that the antithrombotic potential of D involves the ability of the drug to affect the generation of free radicals by leukocytes and suggest that future in vivo studies for the evaluation of the activity of D should take into account the role of monocytes in hemostasis and throm

ISSN:1424-8832    

DOI:10.1159/000216211

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Thirty-two patients suspected of deep venous thrombosis (DVT) of the leg were evaluated after simple plasma tests (latex D-dimer and Elisa D-dimer) against echography and phlebography as the gold standard of DVT. Seven patients showed negative results in the latter test. The classification conformity between the D-dimer methods amounted 84.4%. With regard to the diagnostic classification a high specificity of 100% was found for the latex D-dimer test at the cut-off level of 450 ng/ml, whereas for sensitivity, 96% was reached. The Elisa D-dimer test was striking by its high sensitivity of 100%, but its low specificity of 28.5 %. In summary, these results demonstrate that when there is a suspicion of DVT according to the clinical symptoms, a negative latex test may reject the diagnosis, whereas the latex test is less useful to establish the diagnosis. On the contrary, the Elisa .D-dimer test has a too high false-positive rate. The latex D-dimer test seems to be a reliable tool to exclude the diagnosis after which an ascending contrast venography can be omitted.

ISSN:1424-8832    

DOI:10.1159/000216212

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Cathepsin G and elastase from human polymorphonuclear leucocytes were used in vitro to digest human factor X. Clotting assays showed that both proteinases affected a rapid loss in the coagulant activity of factor X. Calcium ions almost totally protected the coagulant activity of factor X against the action of cathepsin G but not elastase. Polyacrylamide gel electrophoresis (in nonreducing conditions and in the presence of SDS) indicated that the proteolytic action of cathepsin G led to the removal of a peptide of low molecular mass (pX) with the consequent formation of a single stable high molecular mass product (PX). SDS electrophoresis (under reducing conditions and in the presence of SDS) indicated that a pX was derived from the light chain of factor X. The proteolytic action of elastase led to the formation of numerous degradation products. Analysis of the products generated by the action of cathepsin G indicated that cathepsin G cleaved position Phe40:Trp41 in the light chain of factor X. In the presence of citrated plasma, cathepsin G but not elastase, was responsible for a loss in coagulant activity.

ISSN:1424-8832    

DOI:10.1159/000216213

出版商:S. Karger AG    

年代:1991

数据来源: Karger

摘要:

Forty-eight patients with freshly diagnosed carcinoma of the lung (40 males, 8 females) were evaluated for a coagulation profile including activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen, F VIII R:Ag, fibrin monomers (FM), thrombin-antithrombin-III complex (TAT-III), D-dimers and the platelet count. Thirty-eight patients had a normal aPTT and 37 patients a normal PT. None of the patients had clinical or laboratory indications of serious hemorrhage or thrombosis. On the other hand, high percentages of increased values were found for fibrinogen and F VIII R:Ag, which can be seen as prethrombotic factors. The very high percentages of elevated results for the FM, TAT-III and .D-dimer are strongly indicative for low-grade coagulation activation with reactive fibrinolysis. Nevertheless, most lung cancer patients are able to maintain a normal or near normal hemostatic function. The results shown here are indicative of a coagulation and fibrinolysis equilibrium at an enhanced level and demonstrate why an unbalance between the two systems can result in thrombotic complications in (lung) cancer patients as earlier reported.

ISSN:1424-8832    

DOI:10.1159/000216214

出版商:S. Karger AG    

年代:1991

数据来源: Karger