摘要:

We investigated the anticoagulating and heparin-neutralizing properties of protamine and polybrene (hexadimethrine bromide), using the endogenous thrombin potential (ETP) as the parameter to access plasma coagulability. The hypocoagulability induced by high doses of heparin (3 IU/ml) could be reversed by addition of protamine to a very limited extent only. Polybrene on the other hand did neutralize heparin at the equivalent concentration and a two-fold excess did not influence the ETP parameters. In vivo neutralization of high-dose heparin with protamine should therefore be reconsidered. Our experiments suggest polybrene to be superior over protamine with respect to neutralization of high doses of heparin.

ISSN:1424-8832    

DOI:10.1159/000217181

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Monocytes/macrophages actively regulate both the assembly and function, as well as the substrate specificity, of various coagulation enzymes at their membrane surface. Regulation is effected through a variety of mechanisms, not limited to, but including the expression of receptors (or ‘binding sites’) for the various protein constituents of the complexes, the expression of different receptors which may alter the function of the protease, and the expression of membrane proteases which may affect protein cofactor function. Monocyte stimulation with various agonists modulates many of these responses as does their adherence to and differentiation on various substra

ISSN:1424-8832    

DOI:10.1159/000217230

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Thrombotest® results expressed in international normalized ratio (INR) values, obtained in 108 patients on oral anticoagulant treatment, were compared with prothrombin time (PT) results with a recombinant thromboplastin. The former results were obtained on an Amelung coagulometer, the latter on a photo-optical instrument. Using the Thrombotest method, performed within 2 h after sampling as the reference method, a first group of 63 patients had an INR value between 2 and 4. This group was considered as adequately anticoagulated and served as a true positive population in further analysis. The remaining 45 patients (true-negative group) had an INR value below 2 or higher than 4 and could thus be considered as inadequately anticoagulated. Using these definitions, a sensitivity of 86% and a specificity of 96% could be calculated for the PT with the recombinant thromboplastin. All tests from patients on oral anticoagulant treatment were also performed after 24 h storage of the blood or plasma samples at room temperature. When we compared the reference Thrombotest results with those of the late Thrombotest and the late PT recombinant thromboplastin, sensitivities of 86 and 86% as well as specificities of 91 and 96% were found, respectively. In conclusion, PT with a recombinant thromboplastin on a photo-optical instrument, even after prolonged storage of the plasma samples at room temperature, can be considered as suitable for oral anticoagulation control

ISSN:1424-8832    

DOI:10.1159/000217182

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Coagulation reactions normally occur on cell membranes in vivo. Using a cell-based in vitro model system, we have shown that where a factor is located, not simply how much is activated, is critically important in determining its role in hemostasis. Factor Xa activated on a tissue factor (TF)-bearing cell is not equivalent to factor Xa activated on a platelet surface. Factor IX and factor VIII are required for hemostasis because they combine to generate factor Xa on the platelet surface. Factor X activation by factor VIIa/TF does not compensate for a lack of factor IX or VIII because the factor Xa activated by VIIa/TF is located on the wrong surface for efficient thrombin generation.

ISSN:1424-8832    

DOI:10.1159/000217233

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Plasma levels of selected coagulation and fibrinolytic parameters (activated partial thromboplastin time, prothrombin time, fibrinogen, antithrombin III, protein C, thrombin-antithrombin III complexes (TAT), plasminogen activator inhibitor-1 (PAI-1), plasminogen, α2-plasmin inhibitor) were evaluated in 90 patients with clinical suspicion of pulmonary embolism (PE). Plasma levels of fibrinogen, PAI-1 and TAT were significantly higher in patients than in controls (p < 0.01): evaluation of TAT displayed a sensitivity of 96.1% and specificity of 30.8%, and positive and negative predictive values of 64.5 and 85.7%, respectively. The number of nonperfused lung segments correlated directly with TAT levels (p < 0.01) and inversely with arterial pO2 values (p < 0.01). No significant difference was found in the other parameters between patients and controls. Our results suggest that the finding of normal TAT plasma levels can help to exclude PE in patients with clinically suspected PE

ISSN:1424-8832    

DOI:10.1159/000217183

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Tissue factor (TF) is inducibly expressed within the vasculature by monocytes and endothelial cells. Transcriptional activation of the TF gene in these two cell types by bacterial lipopolysaccharide (LPS) or cytokines appears to be regulated by a common mechanism. Functional studies identified a 56-bp LPS response element which contains two AP-1 sites and a kB site. Assembly of a multiprotein complex composed of Fos-Jun and c-Rel-p65 heterodimers is required to induce TF gene transcription. Inhibiting proteolytic degradation of IκBα prevents nuclear translocation of c-Rel-p65 heterodimers and blocks inducible TF expression in monocytic and endothelial cell

ISSN:1424-8832    

DOI:10.1159/000217234

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Localised extravascular initiation of mammalian haemostasis is achieved by the anatomical localization of tissue factor (TF) around blood vessels and at organ surfaces. TF avidly binds factor VII from outflowing blood following vascular injury, forming the tissue factor/factor VII (TF.VII) complex. This is rapidly converted to TF.VIIa, the active initiator of blood coagulation. Structural studies have revealed that the extracellular region of TF consists of two C2-type immunoglobulin-like modules rigidly held at an angle of 125° by an extensive buried interface. The regions of TF involved in binding factor VII extend from the binding finger of the domain interface across quite a wide surface of the distal (N-terminal) module. Solution scattering studies show that both TF and factor VII adopt an extended conformation in solution and that the complex is formed by a compact side by side alignment of the two proteins along their long axes

ISSN:1424-8832    

DOI:10.1159/000217235

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We have earlier shown that both full-length and truncated glycosylated tissue factor pathway inhibitor (TFPI) lacking the third Kunitz domain and the c-terminal region has an antithrombotic effect comparable to low-molecular-weight heparin (LMWH) in an experimental venous thrombosis model. The aim of this study was to investigate whether a recombinant truncated non-glycosylated TFPI (117QTFPI1-161) had an antithrombotic effect similar to the glycosylated TFPI1-161 and LMWH. We also followed the coagulation parameters. The thrombi were induced in rabbit jugular veins with a combination of endothelium destruction and restricted blood flow. Group 1: placebo; group 2: LMWH 60 anti-Xa IU/kg, i.v.; groups 3 and 4: TFPI1-161 0.8 and 0.2 mg/kg, i.v., respectively; groups 5 and 6: 0.8 and 0.2 mg/kg 117QTFPI1-161, i.v., respectively, in a randomized double-dummy fashion. Twelve animals were included in the placebo group and 6 in each of the other groups. The frequency of thrombosis and also of occlusive thrombosis was reduced in all groups compared to placebo. The thrombus weight was reduced (0-9.9 mg) in all groups, significantly in groups 2, 4 and 5 (p = 0.004-0.02) compared to placebo (21.1 mg). In group 3, a borderline p value was achieved (0.06 likely a β-error). The two forms of TFPI1-161 given in the higher doses showed a significantly greater increase of anti-Xa activity, but with a shorter duration compared to LMWH (1.7-1.9 vs. 0.9 anti-Xa IU/ml). Activated partial thromboplastin time (aPTT)-analysis revealed that only LMWH (52 s) caused a significant transient elevation 2 min after injection. In the other groups, a temporary but insignificant elevation of aPTT (27-37 s) was seen. No detectable effect on anti-Xa activity and prothrombin time (PT) was seen in any TFPI group. The glycosylation of the second domain on TFPI does not substantially contribute to the antithrombotic effect of TFPI. Regardless of the glycosylation of TFPl1-161, it has a dose-dependent effect on anti-Xa, a small effect on the aPTT, but no effect on anti-Xa and PT. LMWH has a more pronounced and sustained impact on these parameters

ISSN:1424-8832    

DOI:10.1159/000217184

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Tissue factor is both a trigger of blood coagulation and a true receptor inducing an intracellular signal upon binding of its ligand factor VII to its extracellular parts. When induced in endothelial cells more than 75% of tissue factor antigen was found on the apical side of the cell.

ISSN:1424-8832    

DOI:10.1159/000217236

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

We investigated the role of αIIbβ3 in microparticle generation by normal and thrombasthenic platelets stimulated with collagen plus thrombin. Microparticle generation by normal platelets was scarcely inhibited by monoclonal antibodies for glyco-protein lb and glycoprotein IX. Although one monoclonal anti-α αIIbβ3 antibody (NNKY1-32) partly inhibited microparticle generation, 3 other monoclonal anti-α αIIbβ3 antibodies had little effect. However, the combination of 4 monoclonal anti- αIIbβ3 antibodies or treatment with a polyclonal anti- αIIbβ3 antibody significantly inhibited microparticle generation (p < 0.05). Microparticle generation by thrombasthenic platelets also occurred after stimulation with collagen plus thrombin, although at a significantly lower level compared with normal platelets. Monoclonal antibodies for resting αIIbβ3, P-selectin, activated αIIbβ3 and β2-glycoprotein I bound to microparticles from healthy platelets. In contrast, only a monoclonal antibody for β2-glycoprotein I bound to thrombasthenic microparticles. These results suggest that microparticle generation by collagen plus thrombin occurs via two different mechanisms which are dependent and independent of αIIbβ3, respectively. The αIIbβ3-dependent mechanism appears to require activation of α

ISSN:1424-8832    

DOI:10.1159/000217185

出版商:S. Karger AG    

年代:1996

数据来源: Karger