摘要:

We investigated annexin V expression and membrane vesiculation during activation of four leukemic cell lines (U937, HL60, HEL, and CMKl 1-5) in order to determine whether annexin V had a role in the coagulation abnormalities related to malignancy. After stimulation by tissue plasminogen activator, binding of a monoclonal anti-annexin V antibody to U937 cells and HL60 cells increased in comparison with binding to control cells. Stimulation with thrombin or lipopolysaccharide also induced such an increase, but U46619 did not. Following activation of U937 and HL60 cells with thrombin and lipopolysaccharide, microparticle formation increased. Tissue plasminogen activator caused an increase of micropar-ticles in U937 cells, but not HL60 cells. On the other hand, CMKl 1-5 and HEL cells did not show any increase of micro-particles. These results suggest that some agonists can potently stimulate expression of prothrombinase activity by U937 and HL60 cells. This response appears to be related to cell membrane vesiculation induced by thrombin, tissue plasminogen activator, or lipopolysaccharide, which results in the release of microparticles with binding sites for annexin V. In addition, endogenous annexin V released by leukemic cells may modulate the thrombotic activity of these microparticles.

ISSN:1424-8832    

DOI:10.1159/000217466

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Crohn’s disease has frequently been associated with coagulation abnormalities, causing intravascular deposition of fibrin and local infarction which can subsequently compromise the gut mucosa. Also, arterial and venous thromboembolic complications of larger vessels appear to be associated with Crohn’s disease. Coagulation activation in patients with Crohn’s disease could be a result of increased serum and tissue levels of cytokines, as reported. We prospectively studied parameters of coagulation and fibrinolysis in 10 patients with active Crohn’s disease, who were subsequently treated with a monoclonal anti-tumor necrosis factor-α (TNF) antibody. Ten consecutive patients with active Crohn’s disease (CDAI > 150), not responding to a daily dose of at least 20 mg predniso-lone, received a single infusion of human/mouse chimeric anti-TNF antibody cA2. All evaluable patients attained complete clinical and endoscop-ic remission within 4 weeks. Pretreatment plasma concentrations of markers of thrombin generation, thrombin-antithrombin (TAT) complexes and Fl + 2, were increased (22.1 ± 11.8 μg/1 and 3.46 ± 1.2 nmol/l, respectively). After treatment with cA2, these levels almost completely normalized within 2 weeks. D dimer plasma levels were increased at baseline (377 ± 61.3 μg/1) and decreased to normal levels after cA2 treatment. The levels of plasminogen activator inhibitor (PAI-1) were elevated before treatment and slowly decreased hereafter. The levels of tissue-type plasminogen activator (t-PA) remained unchanged. Von Willebrand factor (vWf) levels were increased at baseline (159 ± 21%) and showed a downward trend after 2 weeks (121.3 ± 24%, NS). In conclusion, anti-TNF antibody infusion resulted in a decrease of thrombin generation and endothelium activation markers in patients that were suffering from steroid-refractory Crohn’s disease. These findings support the notion that active Crohn’s disease is associated with the activation of coagulation and may indicate that this coagulation activati

ISSN:1424-8832    

DOI:10.1159/000217467

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The role of blood platelets in the pathogenesis of malaria remains unclear. In this study we investigated the role of experimentally caused thrombocytopaenia in chronic (Balb/C) and acute (CBA/J) Plαsmodium-berghei-induced murine malaria. A group of 30 Balb/C mice were rendered thrombocyto-paenic by injection of anti-mouse platelet serum given every 2 days from day 2 to day 8 after malaria infection. Compared with the control group, thrombocytopaenic mice showed a greater mortality. The Kaplan-Meier estimate of the risk of death was 4.37-fold higher in the thrombocytopaenic group. Parasitaemia and weight loss was in agreement with the protective effect of platelets. In the acute malaria model, the survival rate was less significant but the estimated risk of death was 1.7-fold higher in the treated group. These results suggesting a protective role of platelets in murine malaria are not in line with previous reports of the literature. Taken together our data suggest, however, that platelets, similarly to some inflammatory cytokines like TNF, play a dual role in the pathogenesis of malaria. Depending on experimental conditions, e.g. the time of onset of thrombocytopaenia, the beneficial role of platelets may outweigh the deleterious one

ISSN:1424-8832    

DOI:10.1159/000217468

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

A 75-year-old male presented with new symptoms of a bleeding diathesis associated with a decline in the functional activity of von Willebrand factor (type 2a von Willebrand’s disease). Replacement therapy was ineffective and he was subsequently treated with intravenous immunoglobulm (Ivlg). Ivlg not only caused symptomatic improvement but was shown to transiently restore the depleted von Willebrand factor intermediate and high molecular weight multimers. Subsequent periodic Ivlg infusions have been used successfully to treat bleeding complications in this patient over the past 3 years. A secondary cause for the acquired von Willebrand’s disease has not been identif

ISSN:1424-8832    

DOI:10.1159/000217469

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

We compared the sensitivity and specificity of a tissue factor-based assay (FVR) with the addition of a phospholipid/silica preparation, to the commercially available aPTT-based method, APCR (CoatestTM), and a modified aPTT-based method (APCM) which utilized factor V-depleted plasma, for the detection of the factor V Leiden mutation. A total of 110 patients were included in this study. This included 32 patients on coumadin therapy, 7 patients on heparin therapy, 5 patients on both anticoagulants therapy, and 24 patients who were positive for anticardiolipin antibody (ACL) and/or lupus inhibitor (LI). Our data demonstrate that the FVR is not affected by anticoagulation treatment or ACL/LI antibodies, whereas in the APCR method, 33 patients cannot be determined either due to the anticoagulant therapy or presence of the ACL and/or LI. With the APCM method, the clotting end-point could not be determined in 1 patient due to the presence of a strong LI. The additional phospholipid/silica material utilized in the FVR enhanced the APC degradation of factor Va and therefore sharpened the demarcation between the factor V Leiden-positive and -negative patients. The sensitivity for the APCR, APCM and FVR was 42, 97 and 100% respectively. The specificity for the APCR, APCM and FVR was 94,96 and 100% respectively.

ISSN:1424-8832    

DOI:10.1159/000217470

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Postprandial triglyceridemia and ‘remnantemia’ may better reflect the atherosclerotic risk than triglyceride (TG) levels in the fasting state. Recently, a new method was developed based on a monoclonal antibody recognizing an epitope distal to the carboxyl end of apo B48 which allows easy measurement of remnant-like lipoproteins (RLP). This study was performed in order to investigate RLP response to a standardized fat meal and establish a normal diurnal pattern of RLP in blood and compare it to platelet aggregation and fibrinolysis in healthy young men. We investigated 7 male volunteers (age range 18-23 years) who received a standardized fat meal (Othsuka Pharmaceutical Company, Japan) containing 32.9% lipids, 2.5% protein, 2.5% carbohydrate, 0.3% calcium and 0.1% phospholipids, and 74 mg/100 g cholesterol (C) at 7:30. The energetic value of this cocktail was 341 kcal/l00 g. Area under curve (AUC) responses in TG, RLP-TG and RLP-C after the meal were as follows: for TG 28.66 ± 8.94; for RLP-TG 17.54 ± 5.55; for RLP-C 1.27 ± 0.42 mg × dl-1 × h-1. These responses were correlated to each other. Surprisingly, collagen-induced platelet aggregation in whole blood was negatively related to RLP-C AUC. Fluctuation patterns of TG, RLP-TG and RLP-C concentrations during the day were remarkably similar, peaking in this particular group of subjects at 10:00-12:00 and at about 23:00, whereas cholesterol was decreasing late in the night and very early in the morning. This pattern was different from those of platelet aggregation and fibrinolysis parameters. Fibrinolysis parameters (t-PA, total PAI-1 free PAI-1 euglobulin clot lysis time) showed a diurnal profile peaking in the morning with nadir between 14:00 and 23:00. ACTH and cortisol profiles (determined on a separate occasion) were remarkably similar to variations in t-PA, total and free PAI-1. Suppression of endogenous ACTH and cortisol synthesis by dexa-methasone did not influence morning levels of t-PA, total PAI-1 free PAI-1 and PAI-1 in complex with tPA. In conclusion, we have demonstrated that in young healthy men circadian changes in serum lipids, such as RLP-C, RLP-TG, total C and TG have little influence on platelet aggregation. Their time course during the day was also different from fibrinolytic components. It seems that the diurnal rhythm of these processes is determined by different me

ISSN:1424-8832    

DOI:10.1159/000217471

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000217472

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000217473

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:1424-8832    

DOI:10.1159/000217465

出版商:S. Karger AG    

年代:1997

数据来源: Karger