摘要:

Tissue factor pathway inhibitor (TFPI) is primarily synthesized by vascular endothelial cells and is foundin vivoin association with endothelial cells, lipoproteins, or in free form. Free TFPI is the most potent and important type, because it is released from endothelial cells following an injection of heparin, or as a result of pathological stimuli. In order to study the role of TFPI in disease, the concentration of free form TFPI was measured in the plasma of 114 patients suffering from disseminated intravascular coagulation (DIC), as the result of several underlying diseases. Plasma antigen levels of free TFPI were significantly higher even in those patients not exhibiting DIC than in normal healthy subjects. These levels were even higher among patients exhibiting DIC, especially those with acute promyelocytic leukemia or cancer, receiving continuous heparin drip infusions. A significant correlation was observed between the plasma antigen levels of free form TFPI and those of fibrin/fibrinogen degradation products, and free form TFPI and plasmin inhibitor complex (r= 0.428,P< 0.0001 andr= 0.329,P< 0.0001, respectively) among 114 DIC patients. There were no significant differences between the plasma levels of free TFPI in DIC patients with or without multiple organ failure. It has been suggested that the plasma levels of free TFPI are closely related to the levels of fibrinolysis occurring in DIC patients, although further study is required to clarify the degree to which TFPI is expressed by endothelial cells during DIC.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We performed a prospective, randomized, open study in 109 outpatients under chronic anticoagulation with acenocoumarine, presenting with International Normalized Ratios (INRs) ⩾ 6.0 and no or minor bleeding. All the patients withheld one dose of acenocoumarine; in addition, a treated group also received 1 mg oral vitamin K1. We aimed at a post-intervention INR < 6.0, with a target zone of 2.0–4.0. The INRs were lowered from a mean of 8.1 ± 1.7 to 4.9 ± 2.5 in the controls (P= 0.0000) and from 8.4 ± 2.4 to 3.3 ± 3 in the treated patients (P= 0.0000). There were no differences in the percentage of patients with post-intervention INRs < 6.0 or within the therapeutic zone. One-third of the treated patients and only 2% of the controls reached INRs < 2.0 (P= 0.0003). Oral vitamin K1offered no advantage to the simple discontinuation of one dose of acenocoumarine. A substantial number of treated patients were consequently exposed to under-anticoagulation.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Abnormalities of coagulation or fibrinolysis play a role in the pathogenesis of coronary artery disease (CAD). Elevated plasma levels of fibrinogen, von Willebrand factor antigen, plasminogen activator inhibitor-1 and tissue-type plasminogen activator were reported to be predictive for reinfarction and death in patients with CAD. We investigated the risk for coronary re-events associated with 18 hemostatic and fibrinolytic parameters in a prospective study including 200 survivors of myocardial infarction (MI). During a 2-year follow-up, 37 patients suffered one of the following predefined re-events: fatal MI (n= 2), non-fatal MI (n= 5), percutaneous transluminal coronary angioplasty (n= 17) or coronary artery bypass grafting (n= 13). Low plasmin–α2-antiplasmin complex (PAP) plasma levels were associated with an up to fivefold (95% confidence interval, 1.6–15.3) increase in relative risk. The association between decreasing PAP levels and coronary re-events remained significant (P =0.004) after correction for possible confounders using multiple logistic regression analysis. Our data indicate low PAP plasma levels to be associated with subsequent coronary events in patients with a history of MI.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Failure to suppress thrombin generation during cardiac surgery promotes fibrin generation, fibrinolysis, and a consumptive coagulopathy. Acquired deficiencies of antithrombin III may play a contributory role. We hypothesized that antithrombin III supplementation to normal physiologic concentrations would decrease thrombin generation and potentially reduce peri-operative bleeding. Twenty patients undergoing coronary artery bypass graft surgery were randomized for this prospective, double-blind, placebo-controlled study. Ten patients received antithrombin III supplementation (50 U/kg) by intravenous infusion prior to incision, and 10 patients received a placebo. Blood samples were obtained pre-operatively, at 1 and 2 h following initiation of cardiopulmonary bypass (CPB), and at 1, 3, and 24 h after completion of CPB. Samples were analyzed for antithrombin III, thrombin–antithrombin III (TAT) complex, and D-dimer concentrations. Cumulative blood loss was recorded at 6 and 12 h after CPB. No statistically significant differences in patient demographics or total heparin dose administered were observed between groups. As expected, plasma antithrombin III concentrations were maintained near pre-operative values in the treatment group, but not in the placebo group. Despite this difference, no statistically significant alterations in generation of TAT complex, D-dimer, or blood loss occurred between groups. Antithrombin III supplementation to maintain normal physiologic concentrations during CPB did not alter significantly thrombin generation, fibrinolytic activity, or blood loss in adults undergoing elective cardiac surgery.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

A simple, rapid and cost-effective method for the analysis of three of the most widely screened genetic risk factors for thrombosis has been established. The protocol developed uses blood spots stored on filter paper (Guthrie spots) as well as DNA extracted from anticoagulated blood. The use of Guthrie spots taken at birth enables the retrospective study of patients who develop thrombotic complications without necessitating resampling. Following isolation of DNA, conventional fluorescence-labelled polymerase chain reaction (PCR) is performed using a thermostable DNA polymerase. Denatured, single-stranded PCR products are analysed on a semi-automated capillary-based genetic analyser, the data being stored electronically. This sensitive protocol obviates the need for endonuclease digestion and the associated gel running and documentation, and leads to a reduction in the recurrent costs of laboratory consumables.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

We compared a functional (amidolytic) and an enzyme-linked immunosorbent assay (ELISA) method for determining aprotinin concentration in 82 plasma samples obtained from patients undergoing cardiac surgery with aprotinin therapy. There was good correlation between methods (r= 0.87); however, aprotinin measurements by chromogenic assay were significantly higher than by ELISA [234 ± 104 kallikrein inhibitory units (KIU)/ml versus 155 ± 88 KIU/ml;P= 0.0001]. This appeared to be attributable to differences in the potency of the material used to standardize the assays. When results were corrected to allow for potency of the standard, there was no significant difference between chromogenic and ELISA methods (234 ± 104 KIU/ml versus 240 ± 137 KIU/ml), although the ELISA results tended to be higher in some samples. These data suggest that aprotinin concentrations measured by these methods cannot be used interchangeably, and care must be taken when interpreting data from studies measuring aprotinin.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Abnormal platelet activation and an increased risk of thrombosis are frequent findings in cancer. As soluble adhesion molecule P-selectin is being increasingly recognized as reflecting increased platelet activation, we hypothesized raised levels in patients with cancer, obtaining plasma from 24 patients with a cross-section of haematological cancers, 41 with breast cancer, and from an equal number of healthy controls for each patient group. Levels of soluble P-selectin were compared with those of von Willebrand factor (vWf), plasminogen activator inhibitor-1 (PAI-1) activity and fibrinogen (markers of endothelial integrity, fibrinolysis and coagulation, respectively). We found raised soluble P-selectin, fibrinogen and vWf in both patient groups compared with their controls (P< 0.01). vWf and soluble P-selectin were higher in the haematological cancers than in breast cancer patients (by 30 and 74%, respectively; bothP< 0.01). There was no significant difference in levels of PAI-1 between any group. There were no differences in soluble P-selectin or vWf when the data from the women with breast cancer were classified according to tumour size, lymph node involvement or presence of vascular invasion. We conclude that the platelet marker soluble P-selectin is raised in both haematological and breast cancer, and is higher in the former, but is unrelated to the type or stage of breast cancer.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Comprehensive studies of fibrinolysis in non-small cell lung carcinoma have been limited, and assignment of patients to high/low prognosis groups based on arbitrary cut-offs utilizing fibrinolytic measurements is unstandardized. This study was performed in 166 patients to examine the effects of cut-off values determined in three ways. Model 1 assigned patients to one of three equal groups (low, medium, high) based on fibrinolytic measurements made at diagnosis, Model 2 divided patients into low/high groups using median values, and Model 3 grouped according to the parameter being above/below normal range. In model 1, raised plasma fibrinogen, D-dimer and soluble fibrin were positively associated with poorer survival. In model 2, tissue plasminogen activator antigen was additionally related to poorer prognosis. Model 3 identified seven parameters as significantly related to survival, two not identified by the other models becoming significant [plasmin–antiplasmin, tissue plasminogen activator inhibitor-1 (PAI-1) antigen]. Using multivariate analysis, plasma fibrinogen level was the most uniformly significant parameter. Relative risk estimates indicated that raised plasma fibrinogen, soluble fibrin and D-dimer were associated with increased risk of death. Use of the normal/above normal cut-off is recommended to provide the maximum number of significant parameters relating to prognosis, and increased plasma D-dimer, PAI-1 antigen and fibrinogen were most closely related to survival/prognosis.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

The effects of alcohol withdrawal on fibrinolysis were studied in 10 middle-aged male chronic alcoholics institutionalized for withdrawal therapy. All patients were sampled on admission [day 1 (D1)] and 21 days after alcohol withdrawal [day 22 (D22)]. The overall plasma fibrinolytic capacity (OFC) was assayed by measuring the ability of patient plasma to generate D-dimers from a standardized fibrin clot, and tissue-type plasminogen activator (t-PA) and t-PA inhibitor (PAI-1) levels were assayed together with serum cholesterol, triglyceride and cholesterol fractions. At D22, the OFC significantly increased in seven patients [D1 = 10 ± 0.7 μg/h (mean ± SD), D22 = 17 ± 7.4 μg/h;P< 0.01], while t-PA and PAI-1 levels decreased in all patients but two (t-PA: D1 = 16.6 ± 5 ng/ml, D22 = 10.2 ± 3.8 ng/ml;P< 0.001; and PAI-1: D1 = 46 ± 39 ng/ml, D22 = 21 ± 28 ng/ml;P< 0.01). This study clearly demonstrates an increase in overall fibrinolytic activity after alcohol withdrawal, which is mainly due to a decrease in PAI-1 levels. These changes induced by alcohol abstinence might provide clear benefit by reducing the risk of thromboembolic events and particularly of stroke associated with elevated PAI-1 levels described in heavy drinkers.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Most trials of bulb garlic and garlic powder tablets indicate reduced coronary heart disease (CHD) risk in elevated-risk subjects. Most persons taking garlic supplements lack overt risk of CHD. However, no trials have tested steam-distilled garlic oil (GO) capsules with healthy subjects. The objectives of the present randomized, double-blind, placebo-controlled study were to determine whether GO capsules reduce CHD risk in trained male runners. Twenty-seven volunteers (mean age, 28.8 years) completed the study. Each took 12.3 mg/day GO (or placebo) capsules for 16 weeks. Main outcome measures were 95% confidence intervals (CIs) between GO and placebo groups for differences in changes of blood pressure (BP), plasma lipids, total antioxidant status (TAS), low-density lipoprotein (LDL) composition and blood clotting factors. Principal results as mean differences (95% CI) between GO and placebo are: pulse, 2.9 beats/min (−0.8 to 6.7),P= 0.12; systolic BP, −4.5 mmHg (−10.8 to 1.9),P= 0.16; plasma total cholesterol, 0.01 mmol/l (−0.34 to 0.37),P= 0.95; plasma triglycerides, −0.20 mmol/l (−0.43 to 0.03),P= 0.09; plasma TAS, 45 μmol Trolox equivalent/l (−35 to 124),P= 0.26; LDL density, 0.0019 g/ml (−0.0005 to 0.0043),P= 0.12; LDL triglycerides/protein, −0.078 mg/mg (−0.149 to −0.007),P= 0.03; LDL cholesterol/protein, −0.24 mg/mg (−0.69 to 0.22),P= 0.3; LDL TAS/triglycerides, 29 nmol/mg (11, 68),P= 0.15; prothrombin time, 0.99 s (−0.36 to 2.35),P= 0.14; partial thromboplastin time, 3.0 s (−1.0 to 7.1),P= 0.13. Results were null statistically. Trends with GO were mostly towards lower CHD risk, and a larger study (~150 subjects) is required to test their validity.

ISSN:0957-5235    

出版商:OVID    

年代:2001

数据来源: OVID