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PubMed1995

Usefulness of coagulation markers in staging of gastric cancer.

Thirty-six patients with nonmucinous adenocarcinoma of the stomach, candidates for surgical laparotomy, were studied to evaluate the presence and extent of coagulation disorders in gastric cancer. They were staged according to TNM cancer staging (T: extent of primary tumor; N: lymph node involvement; M: presence of metastases), and a blood sample was collected before surgery. Platelets, platelet factor four (PF4), beta-thromboglobulin (BTG), activated partial thromboplastine time (APTT), prothrombin time (PT), factors five (V) and seven (VII), fibrinogen, cross-linked fibrin degradation products (XDP), fibrinopeptide-A (Fp-A), and antithrombin three (AT III) were assayed. Only fibrinogen, Fp-A, PF4, and factors V and VII were increased in more than 50% of patients. Fibrinogen and Fp-A were positively correlated with T(r = 0.29, p < p < 0.05; and r = 0.35, p < 0.05; respectively), whereas the other parameters did not show any statistically significant relationship with T, N, and M. Considering the subgroups including only the patients with pathological values, Fp-A (31 patients) was positively correlated with N (r = 0.4, p < 0.05), PF4 (25 patients) showed a positive correlation with T and N (r = 0.42, p < 0.05; r = 0.46, p < 0.05; respectively), and a significantly higher median in the presence than in the absence of metastases (median in the M+ subgroup: 42.7 ng/ml, range 38.6 to 102.8; median in the M- subgroup: 33.7, range 20.3 to 85; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed2005

Peptidoglycan and bacterial DNA induce inflammation and coagulation markers in synergy.

Bacterial compounds signal the presence of foreign pathogens in the innate immune system. These microbial components are key players in infectious diseases and implicate toll-like receptors in the activation of inflammation and coagulation. Nevertheless, the existence of a synergistic relationship between peptidoglycan and bacterial DNA on these two physiological responses has not been investigated. The present study reports new findings on the regulation of tumor necrosis factor alpha and tissue factor in peripheral blood mononuclear cells by peptidoglycan and bacterial DNA. These were found to induce tumor necrosis factor alpha and tissue factor simultaneously and in a synergistic manner. These findings provide a new proinflammatory and procoagulant mechanism likely to play a role in sepsis pathogenesis.

Biomarkers↗
PubMed1998

Evaluation of two new integrated adapters for blood drawing in closed blood bag systems: influence on different molecular coagulation markers.

We compared a conventional blood donation bag system (A) with two newly developed ones (B, C) with integrated Y-shaped adapters. The new systems facilitate the withdrawal of blood samples in a closed system under aseptic conditions. The purpose of the study was to determine whether disturbances during blood donation in the different tubings influence the quality of the donated plasma due to activation processes of the coagulation system. In all bag samples from 34 probands for each system, we found higher levels of the global tests (aPTT, TT) compared to intraindividual controls. This was due to a greater amount of anticoagulant in the bag samples. An increase of procoagulant activity was demonstrated for bags A and C. Concerning the fibrinolytic system, values were reduced in all three systems compared to controls. In summary, the quality of the plasma in the three different bag devices was comparable to controls concerning factor activities measured as global tests. The activation of the coagulation system was only slightly higher in the new system B and C than in the conventional one (A). Therefore, the new closed systems are suitable for blood donation and reveal a high coagulation quality of the plasma.

Adolescent↗
PubMed2003

Changes in blood coagulation markers associated with uterine artery embolization for leiomyomata.

PURPOSE: To determine whether a transient hypercoagulable state is induced by the uterine artery embolization (UAE) procedure. MATERIALS AND METHODS: Serial periprocedure blood samples were obtained from 27 patients undergoing the UAE procedure. Five blood samples were obtained from each patient at set time intervals: before the procedure (for baseline determination), immediately before and after embolization of the uterine arteries, 90 minutes after conclusion of the procedure, and between 18 and 24 hours later. Each blood sample was analyzed for the peripheral levels of the following parameters: thrombin-antithrombin complex (TAT), prothrombin fragment 1.2 (F1.2), platelet factor 4 (PF4), D-dimer, and plasmin-alpha(2)-antiplasmin complex (PAP). For each parameter, the baseline values were statistically compared with the pre- and postembolization values for each individual to detect change over time. Overall and global occasion effects for continuous variables were assessed with the Friedman statistic and individual comparisons between occasions with the Wilcoxon signed-rank test. RESULTS: No evidence was found for a difference in coagulability among the five occasions for D-dimer (P =.7645) or PF4 (P =.09). All three of the remaining measures were found to have statistically significant differences (P <.0001 for F1.2, P =.0026 for PAP, and P =.0006 for TAT). No evidence was found for a difference between preprocedure and preembolization levels for these three latter parameters (P =.595 for F1.2, P =.128 for PAP, P =.9705 for TAT). Hypercoagulability potential as measured by prothrombinase and F1.2 generation increased between preembolization samples and each of the successive postprocedure samples (P <.0001, P <.0001, P =.0082), whereas PAP increased at 90 minutes (P =.0023) and TAT increased immediately after embolization (P <.0001). No clinically apparent thrombotic complications occurred among any of the patients studied. CONCLUSIONS: Surrogate markers of hypercoagulability increase as a result of UAE, suggesting that a prothrombotic state may result after the procedure.

Adult↗
PubMed1998

Preoperative values of molecular coagulation markers identify patients at low risk for intraoperative haemostatic disorders and excessive blood loss.

Conventional laboratory investigations of haemostasis like prothrombin time and activated partial thromboplastin time are not useful in predicting and managing intra-operative bleeding complications. In order to establish a possible "perioperative reference range" for thrombin generation prothrombin fragment F1+2 (F1+2) and fibrin degradation (D-dimer) markers, we measured F1+2 and D-dimer concentrations before surgery (but after induction of anaesthesia), 30 minutes into surgery, 10 minutes after the event expected to induce the maximal activation of the haemostatic systems, 90 minutes after surgery and on postoperative days 1 and 2 in 226 consecutive patients. Samples were collected from arterial lines. Twenty patients developed a clinically defined, intraoperative disorder of haemostasis, 206 did not. Patients with an intraoperative disorder of haemostasis had significantly higher preoperative F1+2 and D-dimer concentrations. Preoperative values for F1+2 and D-dimer concentrations above the 75th percentile of patients without an intraoperative disorder of haemostasis indicated a 2.70 to 2.88 fold risk of developing an intraoperative disorder of haemostasis (odds ratios were 3.04, 3.12 and 3.29 for D-dimer, ELISA, F1+2, and D-dimer latex tests, respectively with 95% confidence intervals from 1.20 to 8.46) with negative predictive values of 94%, but positive predictive values of only 16% to 26%. These data suggest that preoperative determination of molecular markers might be helpful in identifying a group of patients at high risk for intraoperative disorder of haemostasis by exclusion of low risk patients. Validation of such an approach requires a prospective trial.

Adult↗
PubMed2006

Long-term behavior of endothelial and coagulation markers in Eisenmenger syndrome.

The long-term behavior of endothelial markers was studied in patients with Eisenmenger syndrome who were subjected to conventional therapy (no vasodilators) and observed for 18 months. Biochemical markers were analyzed comparatively in patients with class II or III symptoms (group 1, n=10) and patients with class IV symptoms (group 2, n=7). Plasma von Willebrand factor antigen (vWF:Ag), thrombomodulin, tissue-type plasminogen activator (t-PA) and its inhibitor (PAI-1), and D-dimer were determined by immunoenzymatic assay at baseline, and at 6, 12, and 18 months. At baseline, the main clinical difference between groups was a decreased peripheral oxygen saturation in group 2 versus group 1 (77+/-5% and 86+/-4%, respectively, p=0.001). Basal vWF:Ag and t-PA were increased and thrombomodulin was decreased in both groups in comparison with controls (p<0.0001), while D-dimer was increased in group 2 only (p=0.0003). In response to treatment, there was a decrease in vWF:Ag in both groups (19% and 23%, respectively in groups 1 and 2, at 18 months vs. baseline, p<0.0001) and t-PA in group 1 (38% vs. baseline, p=0.0485). Plasma vWF:Ag tended to be higher in group 2 in comparison with group 1 during the whole follow-up. Levels of PAI-1 greater than 38.4 ng/mL (upper 90% limit for normals) and D-dimer greater than 500 ng/mL were detected in individual patients (both groups) during the follow-up period. Thrombomodulin remained decreased in both groups. Thus, severity of symptoms in the Eisenmenger syndrome appears to correlate with low oxygen saturation and higher vWF:Ag levels. Improvement of endothelial dysfunction may occur in response to treatment, although increased risk for thrombosis persists, in view of residual abnormalities.

Adolescent↗
PubMed2006

Among inflammation and coagulation markers, PAI-1 is a true component of the metabolic syndrome.

OBJECTIVE: To investigate whether leukocyte count, fibrinogen, von Willebrand factor (vWF) and plasminogen activator inhibitor-1 activity (PAI-1) are increased in subjects with the metabolic syndrome as defined by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) and the World Health Organisation (WHO). DESIGN: Cross-sectional study. SUBJECTS: A total of 520 overweight and obese subjects: 379 women and 141 men, visiting the weight management clinic of a University Hospital. SUBJECTS AND MEASUREMENTS: Waist circumference, triglycerides, HDL cholesterol, blood pressure and fasting glucose were determined, and the presence or absence of the metabolic syndrome according to the NCEP-ATPIII criteria was assessed. In 349 subjects, data on the waist-to-hip ratio (WHR) and albumin excretion rate were available and the WHO criteria were applied. Insulin resistance was defined using the HOMA-IR index. RESULTS: Subjects with the metabolic syndrome according to the NCEP-ATPIII criteria had significantly higher levels of leukocyte count (P < 0.001) and PAI-1 (P < 0.001), while no significant differences were found for fibrinogen or vWF (P > 0.05). Using the WHO criteria, similar results were found except for vWF, where higher levels were found in subjects with the metabolic syndrome. When subjects were classified according to the number of components of the metabolic syndrome, levels of leukocyte count, vWF and PAI-1 activity were significantly different (P < 0.05). In logistic regression analysis PAI-1, gender and leukocyte count were independent determinants of the metabolic syndrome (P < 0.001). CONCLUSION: Evidence for being a true component of the metabolic syndrome is strong for PAI-1, less for leukocyte count and weak for vWF and fibrinogen.

Adult↗
PubMed1995

Monitoring combined antithrombotic treatments in patients with prosthetic heart valves using transcranial Doppler and coagulation markers.

BACKGROUND AND PURPOSE: The combined use of coumarin and low-dose aspirin appears to reduce the risk of systemic embolism at a low risk of bleeding. The remaining incidence of embolism of approximately 2%/y is still high. Methods for real-time detection of embolic events have not been used thus far to monitor the efficacy of therapeutic strategies. They might permit individually tailored, effective treatments. METHODS: The frequency of embolic signals in both middle cerebral arteries was monitored using a two-channel 2-MHz transcranial Doppler system. We examined five patients with mechanical prosthetic heart valves suffering from recurrent cerebral ischemic symptoms despite adequate anticoagulant therapy (international normalized ratio, 3.0 to 4.3). Measurements were performed on coumarin alone (four baseline values) and subsequent to the addition of intravenous (500 mg bolus) and oral (100 mg/d for 10 days) aspirin or intravenous (5000 IU bolus) heparin. The prothrombotic markers thrombin-antithrombin III complex, fibrinopeptide A, D-dimer, and platelet beta-thromboglobulin were measured simultaneously. RESULTS: None of the combined drug regimens led to a significant reduction of the emboli count. The values of thrombin-antithrombin III complex, fibrinopeptide A, and D-dimer were already within normal limits with coumarin alone. The beta-thromboglobulin levels, however, were increased, and additional aspirin or heparin did not reduce them. There was no correlation between the emboli count and the prothrombotic markers or between the prothrombotic markers and the different drug regimens. CONCLUSIONS: The rate of cerebral emboli measured with transcranial Doppler in the group of high-risk patients studied was not influenced by additional antiplatelet therapy. The emboli are likely to be composed at least in part of platelets, and their generation seems not dependent on thrombin or cyclooxygenase. There is an apparent discrepancy between the unchanged rate of emboli during Doppler monitoring found in this and other studies and the partial efficacy of combined treatment with coumarin and aspirin in clinical long-term studies. This may be explained by differences in the composition or size of the emboli.

Administration, Oral↗
PubMedDate not supplied

[Study of intravascular coagulation activation markers in patients with visceral leishmaniasis].

During last decades significant attention has been paid to the increase of protozoal infections including leishmaniasis. The management of this disease is rather problematic. Significant increase of cases of this disease was observed in Georgia as well. The problem of visceral leishmaniasis is very important nowadays. According to references and our clinical experience patients with visceral leishmaniasis are predisposed to bleeding. The objective of our study was the assessment of functional status of hemostasis in patients with visceral leishmaniasis. We have studied the intravascular activation markers of blood coagulation -- the soluble fibrin-monomeric complexes (SFMC) and fibrinogen/fibrin degradation products (D-dimer) in order to reveal the disorders of hemocoagulation. SFMC and D-dimer we studied in 45 patients with visceral leishmaniasis before and after treatment (with 20-25 day intervals). One patient with severe generalized bleeding died within 72 hours of admission. SFMC measurements were conducted by the orthophenantroline test (Renam, Russia). D-dimer level was measured using FDP-Slidex Direct kit (Bio-Meriou, France). Especially high levels of SFMC and D-dimer have been revealed in cases of severe form of visceral leishmaniasis. SFMC level was increased by 80% (p=0,003), and D-dimer level by 95,6% (p=0,023). There was correlation between numbers of platelets and intravascular blood coagulation markers. Investigation of SFMC and D-dimer showed that in case of visceral leishmaniasis activation of intravascular coagulation takes place, particularly during the severe forms of the disease. Study of these markers is of the diagnostic and prognostic importance and for the initiation of treatment at an early stage of infection, which may potentially avoid the possibility of developing an uncompensated DIC.

Adolescent↗
PubMed2002

Advanced prostate cancer activates coagulation: a controlled study of activation markers of coagulation in ambulatory patients with localized and advanced prostate cancer.

Cancer and increased age are risk factors for coagulation activation. Patients with advanced prostate cancer, which usually presents in the seventh to eighth decade of life, are likely to be at increased risk for thrombosis. We report results of a controlled study of changes in specific and sensitive markers of coagulation activation in patients with prostate cancer. Complete blood count, prothrombin time, partial thromboplastin time, prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin complex (TAT) and quantitative D-dimers (DD) were measured in 30 patients of advanced prostate cancer (androgen ablated), in 30 newly diagnosed localized prostate cancer patients, in 30 healthy age-matched volunteers, and in 20 healthy young volunteers. Plasma F1 + 2 (P < 0.05) and DD (P < 0.05), but not TAT, were significantly elevated in healthy elderly males (mean age, 77 years) when compared with healthy young volunteers (mean age, 35 years). F1 + 2, TAT and DD were significantly elevated in advanced prostate cancer when compared with healthy age-matched controls (P < 0.001). In conclusion, advanced prostate cancer patients have significantly increased levels of sensitive markers of coagulation activation compared with healthy age-matched controls. This data can be used to plan studies to determine the risk of clinically significant coagulopathy and the role of primary prophylaxis in patients with advanced prostate cancer.

Adult↗
PubMed2004

Serial changes in fibrinolysis and coagulation activation markers in acute and convalescent phase of ischemic stroke.

BACKGROUND: The changes in the activity of a number of plasma markers of coagulation and fibrinolysis have previously been studied in patients with ischemic stroke, with conflicting results. We aimed to find out the changes in the activities of a wide array of markers of the coagulation and the fibrinolytic system of mildly or moderately affected first-ever ischemic stroke patients. METHODS: In a prospective, longitudinal, case-control study, we studied plasma plasminogen activator inhibitor type-1 (PAI-1) activity, tissue-type plasminogen activator antigen (t-PA:Ag), d-dimer, prothrombin fragment 1+2 (F 1+2), and thrombin-antithrombin III complex (TAT) levels in 55 consecutive patients on admission, 1 week, 1 month, and 3 months after an ischemic stroke. Sex- and age-matched controls were studied once. All patients underwent blood sampling at each study time point; comprehensive stroke risk factors were recorded, and the etiology of the ischemic stroke was determined. All patients were contacted 3 years later for possible recurrent ischemic events. RESULTS: PAI-1 activity was increased in the acute phase and at 3 months, D-dimer levels were significantly higher at 1 week and 1 month after stroke, whereas t-PA:Ag, TAT and F 1+2 levels remained stable during the whole study period. CONCLUSIONS: The changes of the fibrinolytic and coagulation system activity in the patients with mild or moderate ischemic stroke appeared minor compared with the results of previous studies, which included more severely ill patients.

Acute-Phase Reaction↗
PubMed2001

Lifestyle factors and coagulation activation markers: the Caerphilly Study.

Coagulation activation markers are being investigated as risk factors for cardiovascular disease; we examined the contribution of several lifestyle factors to variation in plasma levels of several activation markers measured in a population-based study of 1947 men. Smoking, alcohol, body mass index (BMI), leisure and work activity, social class, and use of prescribed medicines were each examined in turn. Specific assays of fibrin D-dimer and von Willebrand factor (vWF) activity showed similar relationships to lifestyle variables as we observed previously for less specific assays of D-dimer and vWF antigen. D-dimer levels increased with age, in smokers and in men taking prescribed medication, and were negatively associated with leisure time activity. vWF activity increased with age and showed a U-shaped distribution with BMI. Factors VIIc and VIIIc and thrombin-antithrombin complexes were associated with BMI, factor VIIIc and prothrombin fragments 1 + 2 (F1 + 2) were associated with age, activated partial thromboplastin time (aPTT) and F1 + 2 were associated with smoking, and aPTT showed a small negative association with alcohol consumption. We conclude that lifestyle modification has the possibility of favourably influencing several of these risk markers. In particular, cigarette smoking has a possibly reversible effect on coagulation activation (measured by F1 + 2 and D-dimer).

Aged↗
PubMed2004

[Predictive value of coagulative molecular markers for thromboembolism in patients with nonvalvular atrial fibrillation: prospective five-year follow-up study].

OBJECTIVES: Nonvalvular atrial fibrillation is a known risk factor for thromboembolism. This study investigated the use of coagulation markers to predict thromboembolism in nonvalvular atrial fibrillation patients. METHODS: One hundred thirty nonvalvular atrial fibrillation patients (104 males, 26 females, mean age 63.7 +/- 10.7 years) treated at the Sendai Cardiovascular Center from April 1996 to August 1997 were enrolled in this study. Coagulation markers such as prothrombin fragment 1 + 2, thrombin-antithrombin III complex and D-dimer were measured, and the patients were followed up prospectively to October 2001. RESULTS: One hundred and twenty-six patents (100 males, 26 females, chase rate 96.9%) were included in this investigation based on the medical chart and telephone interview. During five-year follow-up, 16 patients had thromboembolism accidents (3.25%/year) and two were suspected to die of thromboembolism. Three patients died of malignant disease, four of heart disease, and five of other diseases. Eight (25.8%) of the 31 patients with high levels of thrombin-antithrombin III complex and 6 (33.3%) of 18 patients with high levels of D-dimer suffered thromboembolism accidents. High thrombin-antithrombin III complex and D-dimer were statistically positive predictive markers for thromboembolism in patients with nonvalvular atrial fibrillation (p < 0.05). CONCLUSIONS: Coagulation markers such as thrombin-antithrombin III complex and D-dimer can predict thromboembolism accidents in nonvalvular atrial fibrillation patients.

Aged↗