Blood Coagulation Markers Research Articles

The effect of a moderate aerobic exercise on the blood coagulation markers in young non-athlete females

The effect of a moderate aerobic exercise on the blood coagulation markers in young non-athlete females

Obesity‐Related Derangements of Coagulation and Fibrinolysis: A Study of Obesity‐Discordant Monozygotic Twin Pairs

Coagulation and fibrinolytic activities are under strong genetic control. We studied the effects of acquired obesity, independent of genetic factors on coagulation and fibrinolysis activities in obesity-discordant healthy monozygotic (MZ) twin pairs. Fourteen obesity-discordant (BMI within-pair difference >3 kg/m(2)) and 10 concordant (BMI difference <2 kg/m(2)) MZ twin pairs were identified from the nationwide FinnTwin16 study. Body composition (dual-energy x-ray absorptiometry), abdominal fat distribution (magnetic resonance imaging), liver fat (magnetic resonance spectroscopy), high sensitivity C-reactive protein, insulin sensitivity (euglycemic hyperinsulinemic clamp), and a panel of different markers of blood coagulation and fibrinolysis in the fasting state were measured. Strong resemblance was observed in most coagulation factors within all twin pairs, with the intraclass correlations ranging from 0.73 to 0.97, P < 0.03. However, the activities of fibrinogen and FIX, FXI, and FXII, and plasminogen activator inhibitor-1 (PAI-1) activities were increased in the obese co-twins (P < 0.05) and strongly correlated with the measures of adiposity, inflammation, and insulin resistance (r = 0.32-0.73, P < 0.05) among the twin individuals. Intrapair differences in fibrinogen and PAI-1 correlated with those in BMI, adiposity, and fasting insulin levels (r = 0.40-0.58, P < 0.05) indicating the independent effect of obesity. Derangements of blood coagulation and fibrinolysis are present already in early adulthood in obese subjects. Acquired obesity, independent of genetic factors, increases the activities of fibrinogen and activities of FIX, FXI, FXII, and PAI-1. This study confirms the mechanisms of simultaneous activities of intrinsic coagulation factors and impaired fibrinolysis predisposing obese subjects to thrombosis.

Enoxaparin and fondaparinux attenuates endothelial damage in endotoxemic rats

Prophylactic use of anticoagulants for septic patients in intensive care unit is a standard therapy for the prevention of venous thrombosis. Moreover, recent studies have demonstrated the anti-inflammatory effects of anticoagulants such as Factor Xa inhibitors and heparins. However, there have been no studies to examine the effects of fondaparinux and enoxaparin when applied in a sepsis model. Therefore, we examined the anti-inflammatory effects and bleeding events when these agents are applied in a lipopolysaccharide challenge model. Wistar rats received lipopolysaccharides followed by a bolus infusion of fondaparinux, enoxaparin, or placebo. Microscopic observation of the mesenteric microcirculation for endothelial damage and measurement of bleeding area after vascular puncture was performed (n = 6 in each group). In another series, blood samples were taken, and blood cell counts, coagulation markers, and organ damage markers were measured (n = 6 in each). Both leukocyte adherence to vascular endothelium and endothelial damage were reduced in fondaparinux and enoxaparin groups. The bleeding area was markedly increased in the fondaparinux group. Coagulation markers were maintained better in the enoxaparin group. Levels of organ damage markers were significantly suppressed in both fondaparinux and enoxaparin groups (p < 0.01, compared with control, each). Fondaparinux and enoxaparin reduce organ dysfunction by decreasing endothelial damage. However, bleeding was more prominent in the fondaparinux group compared with the enoxaparin group at an equipotent dose for anti-Xa activity. Because the setting of this experiment is different from the clinical use, further study is required for the comparison of both pharmaceuticals.

Leisure time emotional excitement increases endothelin-1 and interleukin-6 in cardiac patients

Objectives. Emotional excitement may trigger serious cardiovascular (CV) events. Our objective was to compare the changes in potential surrogate markers of CV events in patients with coronary artery disease (CAD) during emotional excitement and exercise. Design. Fifty-three enthusiastic ice-hockey spectators with stable CAD attended the Finnish national ice-hockey play-off matches and a maximal bicycle exercise. Plasma catecholamines, endothelin-1, interleukin-6, and markers of platelet activation and blood coagulation were determined before and during the match and before and after the exercise. Results. Plasma endothelin-1 (2.82 ± 0.21 vs. 2.94 ± 0.25 pg/mL, p < 0.0001), noradrenaline (4.38 ± 1.79 vs. 4.77 ± 1.75 nmol/L, p = 0.009) and interleukin-6 (2.04 ± 1.98 vs. 2.90 ± 2.41 pg/mL, p < 0.0001) increased during the match, but markers of platelet activation and coagulation remained unchanged. Endothelin-1 did not change during exercise (2.73 ± 0.17 vs. 2.72 ± 0.19 pg/mL, p = 0.593) but noradrenaline (2.70 ± 1.08 vs.10.6 ± 5.5 nmol/L), adrenaline (0.23 ± 0.13 vs. 0.52 ± 0.37 nmol/L), interleukin-6 (1.77 ± 1.59 vs. 2.43 ± 1.78 pg/mL) and markers of platelet activation and blood coagulation increased significantly (p < 0.0001 for all). Conclusions. The responses of surrogate markers of acute CV events to emotional excitement and physical exercise are partly different. Emotional excitement causes concomitant increases in markers reflecting vulnerability to atherosclerotic plaque complications while physical exercise causes more prominent changes in markers of coagulation.

Hypostasis in the heart and great vessels of non-traumatic in-hospital death cases on postmortem computed tomography: Relationship to antemortem blood tests

Objectives The purpose of this study was to investigate hypostasis in the heart and great vessels (HHGV) by postmortem computed tomography (PMCT) in cases of non-traumatic in-hospital deaths and to analyze relationships between clarity of HHGV and antemortem blood markers. Material and methods The study included 31 cadavers of patients who died while receiving treatment in our academic tertiary-care hospital between April and December 2009. Antemortem blood tests including both hematological and blood coagulation markers were performed within 48 h before death, and PMCT and conventional autopsies were performed. The findings of HHGV were assessed in the following six locations: the superior vena cava, right atrium, right ventricle, thoracic aorta, left atrium, and left ventricle. The clarity of HHGV on PMCT was divided into two groups using attenuation of the left ventricular wall as a reference: no/obscure HHGV group and clear HHGV group. The relationships between clarity of HHGV and six blood markers [red blood cell (RBC) count, hemoglobin (Hb), hematocrit (Ht), prothrombin percentage activity (PT%), activated partial thromboplastin time (aPTT), and fibrinogen] were evaluated statistically. Results We observed no/obscure HHGV in 14 patients (45%) and clear HHGV in 17 patients (55%). The level of fibrinogen in clear HHGV group was significantly higher than in no/obscure HHGV group ( P = 0.029). No relationships were found between clarity of HHGV and other five blood markers. Conclusion HHGV is a common PMCT finding. Clear HHGV on PMCT was related to higher level of fibrinogen in non-traumatic in-hospital death cases.

Predictive blood coagulation markers for early diagnosis of venous thromboembolism after total knee joint replacement

Pulmonary embolism development may be prevented if asymptomatic venous thromboembolism (VTE) can be predicted and treated preoperatively or soon after total knee arthroplasty (TKA). The purpose of this study was to evaluate whether asymptomatic VTE can be predicted by blood coagulation markers preoperatively or early after TKA. This prospective single-centre study enrolled 68 patients (6 men, 62 women; mean age: 71 years) who underwent TKA between September 2004 and August 2009. Sixteen-row multidetector computed tomography was performed 4 days before and after surgery for diagnosis of asymptomatic VTE. Blood samples were taken to measure the plasma levels of soluble fibrin monomer complex (SFMC), D-dimer and cross-linked fibrin degradation products by leukocyte elastase (e-XDP) at 4 days preoperatively, and at 1 hour, 1 day and 4 days postoperatively. The preoperative SFMC, D-dimer and e-XDP levels did not differ significantly between the thrombus ( n = 36) and no-thrombus ( n = 32) groups. D-dimer and e-XDP levels showed the most significant increases at days 4 and 1, respectively, after surgery in the thrombus group. With cut-off points of 7.5 μg/ml for D-dimer and 8.2 U/ml for e-XDP, the sensitivities were 75% and 75%, and the specificities were 63% and 59%, respectively. By multiple logistic regression analysis, D-dimer at day 4 and e-XDP at day 1 postoperatively were independent markers for early diagnosis of VTE (odds ratio = 1.61 and 1.19, P = 0.01 and 0.04, respectively). The postoperative occurrence of new asymptomatic VTE may be predicted by D-dimer at day 4 and e-XDP at day 1 after TKA.

In-Traffic Air Pollution Exposure and CC16, Blood Coagulation, and Inflammation Markers in Healthy Adults

Background: Exposure to traffic-related air pollution is a risk factor for cardiovascular events, probably involving mechanisms of inflammation and coagulation. Little is known about effects of the short exposures encountered while participating in traffic.Objectives: The objective of the study was to examine effects of exposure of commuters to air pollution on cardiovascular biomarkers.Methods: Thirty-four healthy adult volunteers commuted for 2 hr by bus, car, or bicycle during the morning rush hour. During the commute, exposure to particle number, particulate matter (PM) ≤ 2.5 µm in aerodynamic diameter (PM2.5), PM ≤ 10 µm in diameter (PM10), and soot was measured. We estimated inhaled doses based on heart rate monitoring. Shortly before exposure and 6 hr after exposure, blood samples were taken and analyzed for CC16 (Clara cell protein 16), blood cell count, coagulation markers, and inflammation markers. Between June 2007 and June 2008, 352 pre- and postexposure blood samples were collected on 47 test days. We used mixed models to analyze the associations between exposure and changes in health parameters.Results: We observed no consistent associations between the air pollution exposures and doses and the various biomarkers that we investigated.Conclusions: Air pollution exposure during commuting was not consistently associated with acute changes in inflammation markers, blood cell counts, or blood coagulation markers.

Effect of edoxaban on markers of coagulation in venous and shed blood compared with fondaparinux

Edoxaban, an oral direct factor Xa (FXa) inhibitor, is in phase III clinical development for stroke prevention in atrial fibrillation and treatment of venous thromboembolism. The shed blood model allows for study of activated coagulation at a site of standardised tissue injury due to local release of tissue factor. The objective of this study was to evaluate the effect of three doses of edoxaban on markers of coagulation in shed and venous blood versus placebo and a standard prophylactic dose of fondaparinux. A total of 100 healthy male subjects were randomised to receive single doses of one of five treatments: subcutaneously administered fondaparinux 2.5 mg; orally administered edoxaban 30, 60, or 120 mg; or placebo. The primary objective was measurement of blood coagulation markers prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin (TAT) complex, and platelet activation marker β-thromboglobulin (β-TG), in venous and shed blood. Secondary objectives included pharmacokinetics, shed blood volume, and safety of edoxaban. Single doses of edoxaban caused rapid and significant decreases of F1+2, TAT, and β-TG in the shed blood model, indicating inhibition of thrombin generation and platelet activation. Inhibition was significantly less for fondaparinux versus edoxaban. Baseline-corrected F1+2, TAT, and β-TG values demonstrated sustained inhibition up to 24 hours for shed blood in the edoxaban groups but no significant inhibition in venous blood. Overall, edoxaban treatments were well tolerated. In conclusion, single oral doses of edoxaban 30, 60, or 120 mg caused rapid and sustained inhibition of coagulation up to 24 hours in the shed blood model.

Complement inhibition decreases the procoagulant response and confers organ protection in a baboon model of Escherichia coli sepsis

AbstractSevere sepsis leads to massive activation of coagulation and complement cascades that could contribute to multiple organ failure and death. To investigate the role of the complement and its crosstalk with the hemostatic system in the pathophysiology and therapeutics of sepsis, we have used a potent inhibitor (compstatin) administered early or late after Escherichia coli challenge in a baboon model of sepsis-induced multiple organ failure. Compstatin infusion inhibited sepsis-induced blood and tissue biomarkers of complement activation, reduced leucopenia and thrombocytopenia, and lowered the accumulation of macrophages and platelets in organs. Compstatin decreased the coagulopathic response by down-regulating tissue factor and PAI-1, diminished global blood coagulation markers (fibrinogen, fibrin-degradation products, APTT), and preserved the endothelial anticoagulant properties. Compstatin treatment also improved cardiac function and the biochemical markers of kidney and liver damage. Histologic analysis of vital organs collected from animals euthanized after 24 hours showed decreased microvascular thrombosis, improved vascular barrier function, and less leukocyte infiltration and cell death, all consistent with attenuated organ injury. We conclude that complement-coagulation interplay contributes to the progression of severe sepsis and blocking the harmful effects of complement activation products, especially during the organ failure stage of severe sepsis is a potentially important therapeutic strategy.

Coagulation/fibrinolysis and inflammation markers are associated with disease activity in patients with chronic urticaria

The evaluation of disease severity and activity of chronic urticaria (CU) is essential for the adequate treatment of patients. However, there is no reliable biomarker for such evaluations. Recently, markers of blood coagulation and fibrinolysis have been revealed to be elevated in severe cases of CU. In this article, we studied the coagulation/fibrinolysis and inflammation markers and their relationship to disease activity in patients with CU. Plasma fibrin degradation products (FDP), d-dimer and serum C-reactive protein (CRP) were measured with the assessment of disease severity and skin reaction to autologous serum in 82 patients with CU and 37 patients with acute urticaria, idiopathic angioedema (AE) or inducible types of urticaria (IU). The levels of FDP in patients with CU were significantly higher than those in patients with IU, but no other differences in FDP, d-dimer and CRP were observed among patients with different types of urticaria. These markers of patients with CU were well correlated with each other and significantly associated with disease severity of CU, but not with skin reactions to autologous serum. In 37 patients with CU, levels of all these parameters reduced as their disease condition improved, while they increased when the disease became aggravated. Regarding FDP, this relationship was observed even if FDP concentrations were within normal range throughout the study. The measurement of plasma FDP, d-dimer and serum CRP may be useful for the assessment of disease activity of CU.

Reduction in postprandial glucose excursion and prolongation of satiety: possible explanation of the long-term effects of whole grain Salba (Salvia Hispanica L.)

Despite strong correlations linking whole-grain consumption to reductions in heart disease, the physiological mechanisms involved remain ambiguous. We assessed whether Salba (Salvia Hispanica L.) whole grain reduces postprandial glycemia in healthy subjects, as a possible explanation for its cardioprotective effects observed in individuals with diabetes. The study used acute, randomized, double-blind, controlled design in which 11 healthy individuals (6 males and 5 females; body mass index 22.3+/-2.8 kg/m(2)) received 0, 7, 15 or 24 g of Salba baked into white bread. Capillary samples and appetite ratings were collected over 2 h after consumption. A dose-response reduction in postprandial glycemia (P=0.002, r(2)=0.203) was observed with all three doses of Salba, significantly decreasing incremental areas under the curve (iAUCs) and time point-specific blood glucose (P<0.05). Appetite ratings were decreased at 60 min after high, 90 min after high and intermediate and at 120 min after all treatments (P<0.05). Decrease in postprandial glycemia provides a potential explanation for improvements in blood pressure, coagulation and inflammatory markers previously observed after 12-week Salba supplementation in type II diabetes.

Acute Myocardial Infarction (AMI) and Intermediate Coronary Syndrome (ICS)

In recent studies it was shown that blood co-agulation and inflammation markers are raising at high geomagnetic activity; acute myocardial infarction and all his subtypes, mostly related to atheromatous plaque disruption with higher Cosmic Ray (Neutron) activity. The aim of this study was to explore AMI and ICS differences by concomitant physical conditions, accompany-ing each of these acute coronary syndromes. The data was a part of MONICA international study in Kaunas, Lithuania in years 2000-2005 (72 consecutive months). 4633 patients with AMI (2461 men) and 961 with ICS (654 men), (age up to 65) were studied. For comparison four indices of Solar (SA), three of Geomagnetic (GMA), Cosmic Ray (CRA) measured by Neutron activity imp/min. were used. Cosmophysical data were from space science institutions in the USA and Russia. Pearson correlation coefficients and their probabilities were obtained.Monthly num-ber of AMI and ICS shows different links with the physical parameters: AMI were significantly in-verse related to SA (r=-0.4, p=0.0021) and direct to CRA (Neutron) activity (r=0.23, p=0.048). ICS was not correlated with these two parameters, but show significant links to GMA (r=0.25, p=0.037). Gender differences were evident, men more close related to changes in the mentioned physical parameters.Conclusion: 1. Monthly nu- mber of AMI and ICS is different related to fluc-tuations of environmental physical parameters. 2. The described connections can affect differ-ences in the pathogenesis of these forms of Acute Coronary Insufficiency.

ENOXAPARIN ATTENUATES ENDOTHELIAL DAMAGE WITH LESS BLEEDING COMPARED WITH UNFRACTIONATED HEPARIN IN ENDOTOXEMIC RATS

Prophylactic use of anticoagulants during sepsis is strongly recommended for the prevention of venous thrombosis. Moreover, recent studies suggested the positive effects of anticoagulants to the inflammation. In this study, we planned to confirm the effects of heparins on protecting against endothelial damage in endotoxemia. In addition, we also examined the differences between unfractionated heparin (UFH) and enoxaparin. Wistar rats received 8.5 mg/kg (i.v.) LPS, followed by a bolus infusion of either 350 U/kg of UFH, 2.0 mg/kg of enoxaparin, or placebo. Microscopic observation of the mesenteric microcirculation and the measurement of the bleeding area after puncture with a microneedle were performed 3 h later (n = 6 in each group). In another series, blood samples were taken 3 h after the LPS injection, and blood cell counts, coagulation markers, and organ damage markers were measured (n = 6 in each). As a result, the leukocyte adherence to the endothelium was significantly reduced in both the UFH and enoxaparin groups, and thus, endothelial damage was attenuated in these groups. The bleeding area was markedly expanded in the UFH group compared with the other groups (P < 0.01 each). The decrease in white blood cells and platelet count was significantly suppressed in the enoxaparin group compared with the UFH group (P < 0.05 each). The fibrinogen level was maintained at significantly better levels, and the elevation of alanine aminotransferase was significantly suppressed in enoxaparin group (P < 0.05 each). In conclusion, both UFH and enoxaparin protect against endothelial damage by preventing leukocyte adhesion. However, UFH significantly increases the bleeding area, whereas enoxaparin does not increase bleeding, and thus, it can reduce organ damages in the endotoxemic rat.

Exposure to ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats

BackgroundExposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. In the present study we sought to investigate the cardiopulmonary responses on spontaneously hypertensive rats (SHRs) following inhalation of UfCPs (24 h, 172 μg·m-3), to assess whether compromised animals (SHR) exhibit a different response pattern compared to the previously studied healthy rats (WKY).MethodsCardiophysiological response in SHRs was analyzed using radiotelemetry. Blood pressure (BP) and its biomarkers plasma renin-angiotensin system were also assessed. Lung and cardiac mRNA expressions for markers of oxidative stress (hemeoxygenase-1), blood coagulation (tissue factor, plasminogen activator inhibitor-1), and endothelial function (endothelin-1, and endothelin receptors A and B) were analyzed following UfCPs exposure in SHRs. UfCPs-mediated inflammatory responses were assessed from broncho-alveolar-lavage fluid (BALF).ResultsIncreased BP and heart rate (HR) by about 5% with a lag of 1–3 days were detected in UfCPs exposed SHRs. Inflammatory markers of BALF, lung (pulmonary) and blood (systemic) were not affected. However, mRNA expression of hemeoxygenase-1, endothelin-1, endothelin receptors A and B, tissue factor, and plasminogen activator inhibitor showed a significant induction (~2.5-fold; p < 0.05) with endothelin 1 being the maximally induced factor (6-fold; p < 0.05) on the third recovery day in the lungs of UfCPs exposed SHRs; while all of these factors – except hemeoxygenase-1 – were not affected in cardiac tissues. Strikingly, the UfCPs-mediated altered BP is paralleled by the induction of renin-angiotensin system in plasma.ConclusionOur finding shows that UfCPs exposure at levels which does not induce detectable pulmonary neutrophilic inflammation, triggers distinct effects in the lung and also at the systemic level in compromised SHRs. These effects are characterized by increased activity of plasma renin-angiotensin system and circulating white blood cells together with moderate increases in the BP, HR and decreases in heart rate variability. This systemic effect is associated with pulmonary, but not cardiac, mRNA induction of biomarkers reflective of oxidative stress; activation of vasoconstriction, stimulation of blood coagulation factors, and inhibition of fibrinolysis. Thus, UfCPs may cause cardiovascular and pulmonary impairment, in the absence of detectable pulmonary inflammation, in individuals suffering from preexisting cardiovascular diseases.

Coagulation function changes and the clinical implication in children with systemic inflammatory response syndrome

Objective To study the coagulation disorder in children with systemic inflammatory response syndrome (SIRS) and their influences on the prognosis. Methods A prospective case-control study was carried out in our ICU. According to the pediatric/neonatal new definition of SIRS, all the patients were divided into 2 groups:SIRS group (24 cases) and non-SIRS group (21 casea), as well as 28 control cases were included. The SIRS group was divided into 2 subgroups:death and survivor subgroup. Levels of platelet (PLT), prothrombin test (PT), activated partial thromboplastin time ( APTT ), fibrinogen (FBG), thrombin antithrombin complex (TAT), antithrombin Ⅲ (AT-Ⅲ), protein C (PC), thrombomodulin (TM), tissue-type plsminogen activator (TPA), D-dimer (DD) were measured in all cases. Results ( 1 ) Levels of PT, APTT, TAT, TM, DD, TPA were significantly higher in SIRS group than those in non-SIRS group and control group ( P 0.05 ). (2) The coagulation indexes of death cases were not significantly different from those of survivors(P > 0.05). Conclusion (1) Patients with SIRS have coagulation disorder, characterized by coagulation activation, anticoagulation consumption and fibrinolysis activation. (2) Molecular markers of blood coagulation are good markers to reflect the different stages of early SIRS. (3) Impact of blood coagulation markers on the patients' prognosis needs to be further evaluated by enlarging the sample size. Key words: Systemic inflammatory response syndrome; Coagulation disorder dysfunction; Molecular markers of blood coagulation; Multiple organ failure

Effect of Fitness-Level on Blood Coagulation Markers After Cold Exposure in Healthy Males

INTRODUCTION: Previous research has elucidated that blood coagulation factors are a contributing factor in the incidence of cardiovascular disease (CVD) and the four to six hours following acute cold exposure (ACE) is a critical time in which there is increased risk for a cardiac event. Furthermore, research has demonstrated a low-dose of aspirin altered the clotting response during recovery from ACE (ACE-REC). In addition, training status or fitness level has been shown to have a positive effect on acute and chronic hematologic function. Therefore, it is uncertain whether the fitness level of individuals who has been fed a body-weight dose of aspirin for one week prior to cold exposure is able to decrease the risk of clot formation during ACE-REC. PURPOSE: To determine the effect of fitness level on markers of coagulation in healthy males who were given a body-weight dose of aspirin during a two hour recovery from exposure to 10°C cold air. METHODS: Ten males (25.6±1.6 y) underwent pre-experimental testing to determine maximal oxygen consumption (VO2max) and body composition. Subjects were then randomly divided into low-fit (LF: VO2 = 36.6 ± 0.9 ml.kg−1.min−1; %BF = 22.9±0.8 %) and high fit (HF: VO2 = 52.0 ±1.2 ml.kg−1.min−1; %BF = 15.5±1.2) groups. Each subject underwent 2 trials which consisted of 120 min of exposure to 10°C air and 120 min of recovery in 25°C air. Blood samples were obtained at baseline, 0, 60, and 120-min of recovery and analyzed for blood markers of blood coagulation. RESULTS: ANOVA did not reveal a main effect for fitness-level for any blood coagulation markers during ACE-REC. CONCLUSION: Based on these data, fitness-level did not contribute to a decrease in coagulation during ACE-REC.

Platelet-derived microparticles and coagulation activation in breast cancer patients

In the mid 1800s Trousseau observed cancer-associated thrombosis, of which the underlying pathogenesis still remains unknown. We performed a prospective study on platelet-derived microparticles (PMP) and their procoagulant potential in breast cancer patients. Fifty-eight breast cancer patients and 13 women with benign breast tumors were included in the study. Microparticles (MP) were examined by electron microscopy and FACS analysis using labels for annexin V (total numbers), CD61 (PMP), CD62P and CD63 (activated platelets), CD62E (endothelial cells), CD45 (leukocytes) as well as CD142 (tissue factor). Prothrombin fragment 1+2 (F1+2) and thrombin generation were measured as blood coagulation markers. Numbers of annexin V+-MP were highest in breast cancer patients with larger tumor size (T2; median = 5,637 x 10(6)/l; range = 2,852-8,613) and patients with distant metastases (M1; median = 6,102 x 10(6)/l; range = 3,350-7,445), and differed significantly from patients with in-situ tumor (Tis; median = 3,220 x 10(6)/l; range = 2,277-4,124; p = 0.019), small tumor size (T1; median = 3,281 x 10(6)/l; range = 2,356-4,861; p = 0.043) and women with benign breast tumor (median = 4,108 x 10(6)/l; range = 2,530-4,874; p = 0.040). A total of 82.3% of MP were from platelets, 14.6 % from endothelial cells and 0.3% from leukocytes. Less than 10% of PMP showed degranulation markers. Larger tumor size (T2) and metastases correlated with high counts of PMP and with highest F1+2 levels. Since prothrombin levels and thrombin generation did not parallel MP levels, we speculate that MP act in the microenvironment of tumor tissue and may thus not be an exclusive parameter reflecting in-vivo procoagulant activity.

Association of D-dimer with microalbuminuria in patients with type 2 diabetes mellitus

Microalbuminuria has been reported to be related to incidence of cardiovascular complications in diabetes. No consistent findings have been obtained on the relationships of microalbuminuria with blood coagulation and fibrinolysis. The purpose of this study was to determine whether microalbuminuria is associated with blood markers reflecting coagulation and fibrinolysis activities in patients with type 2 diabetes. The relationships of albumin excretion rate (AER) with atherosclerosis-related variables, including blood coagulation and fibrinolysis markers, were investigated in patients with type 2 diabetes who showed normoalbuminuria (AER: less than 20 microg/min) and microalbuminuria (AER: 20 microg/min or higher and less than 200 microg/min). AER was significantly correlated with body mass index (BMI), maximum intima-media thickness of common carotid arteries, blood HDL cholesterol, uric acid, creatinine and D-dimer. On the other hand, AER showed no significant correlation with blood platelets, fibrinogen, thrombin-antithrombin III complex, plasmin-alpha2 plasmin inhibitor complex and plasminogen activator inhibitor-1. In multiple regression analysis, using age, sex, BMI, pulse pressure, hemoglobin A1c, HDL cholesterol, uric acid, creatinine, D-dimer and history of anti-thrombotic therapy as explanatory variables, only D-dimer showed a significant correlation with AER. The mean level of log-converted D-dimer after adjustment for age and sex was significantly higher in subjects with microalbuminuria than in those with normoalbuminuria. D-dimer is associated with microalbuminuria in patients with diabetes and this suggests that glomerular dysfunction is in part mediated by hypercoagulability.

Clinical study on the related markers of blood coagulation in the patients with ANFH after SARS

The aim of this research was to investigate the blood coagulation function in the patients with avascular necrosis of the femoral head (ANFH) after severe acute respiratory syndrome (SARS). The expression of CD31, CD61, CD62p, CD63 and PAC-1 on platelet membrane was measured respectively by flowcytometry, and the plasma prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (Fbg) were measured by blood clotting instrument in 26 patients with ANFH after SARS and in 17 healthy adults. The expression of CD31, CD61, CD 62p, CD63 and PAC-1 on platelet membrane in 26 patients was all lower than that in 17 healthy subjects (P < 0.01). The levels of PT, APTT, TT and Fbg in 26 patients were all normal. There is no significant difference (P > 0.05) in those markers between patients and 17 healthy adults. The blood may not be in hypercoagulable state in patients with ANFH after SARS.

Association of pulse pressure with fibrinolysis in patients with type 2 diabetes

Introduction Pulse pressure is a potent risk factor for atherosclerotic disease. The purpose of this cross-sectional study was to determine whether pulse pressure is associated with blood coagulation and fibrinolysis in patients with diabetes. Materials and methods The relationships between pulse pressure and atherosclerotic risk factors, including blood coagulation and fibrinolysis markers, were investigated in subjects with type 2 diabetes. Results Pulse pressure was found to be significantly correlated with blood fibrinolysis markers, such as plasmin–α2–antiplasmin complex (PAP) and D-dimer, but not with platelets and blood coagulation markers, such as fibrinogen and thrombin–antithrombin III complex (TAT). The mean pulse pressure levels in the highest tertiles of PAP and D-dimer were significantly higher than those in the lowest tertiles, while the differences in the mean pulse pressure levels among tertile groups of platelets, fibrinogen and TAT were not significant. These relationships of pulse pressure with PAP and D-dimer were not altered by adjustment for age, sex and history of therapy with antihypertensive and/or antithrombotic drugs. On the other hand, neither systolic nor diastolic blood pressure showed significant correlations with PAP, D-dimer, platelets, fibrinogen and TAT. Pulse pressure was also significantly correlated with age, aortic pulse wave velocity, intima-media thickness of the common carotid arteries and serum sialic acid. Conclusions Pulse pressure is associated with blood fibrinolysis as well as atherosclerotic progression in patients with type 2 diabetes. The results of this study suggest that pulse pressure affects atherosclerotic progression through altering hemostatic functions in patients with diabetes.