Fibrinolytic Factors Research Articles

Thromboembolic Complications in Malignant Haematological Disorders

It is well known that solid cancers are associated with thromboembolic complications, but recent studies have shown that the incidence of thrombosis may be as high (or even higher) in patients with malignant haematological disorders. However, this may be obscured by the significant morbidity and mortality due to other complications of haematological malignancies, such as bleeding and infections. The vast majority of patients with haematological neoplasias also have clinically silent haemostatic abnormalities, but some may show clinical manifestations, including venous thromboembolism, pulmonary embolism, disseminated intravascular coagulation and life-threatening thrombohaemorrhagic syndrome in acute leukaemias. The pathogenesis of thromboembolic disease in haematological malignancies is complex and multifactorial: tumour cell-derived procoagulant, fibrinolytic or proteolytic factors and inflammatory cytokines affect clotting activation, and chemotherapy and anti-angiogenic drugs increase thrombotic risk in patients with lymphoma, acute leukaemia and multiple myeloma. Infectious complications are another important factor: endotoxins from gram-negative bacteria induce the release of tissue factor (TF), Tumor Necrosis Factor (TNF) and interleukin-1b (IL-1b), and gram-positive organisms can release bacterial mucopolysaccharides that directly activate factor XII. Leukaemic patients may be affected by other prothrombotic factors, including hyperleukocytosis, increased TF expression and activation, and the prothrombotic properties of therapeutic agents such as all-trans retinoic acid and L-asparaginase, which can induce thrombosis involving multiple organs. The very high risk of haemorrhaging in these patients warrants prospective randomised trials evaluating optimal anti-thrombotic prophylaxis and treatment.

Association of Thrombotic and Fibrinolytic Factors with Severity of Culprit Lesion in Patients with Acute Coronary Syndromes Without ST Elevation

Increased procoagulant activity and/or impaired fibrinolysis contribute to the development and organization of thrombus, subsequently resulting in complete or incomplete obstruction in acute coronary syndromes (ACS). We investigated the relationship between culprit lesion severity and thrombotic and fibrinolytic parameters in patients who had non-ST elevation ACS (NSTE-ACS). This study included 95 consecutive patients with NSTE-ACS. All patients underwent coronary angiography within the first 72 hours depending on the clinical situation. Stenosis >or=50% in the coronary artery was considered significant. NSTE-ACS patients were then divided into two groups: patients with critical stenosis (n = 53) and patients with noncritical stenosis (n = 35). Plasma levels of D-dimer, fibrinogen, thrombin-antithrombin III complex (TAT), and prothrombin fragment 1 + 2 (PF 1 + 2) were measured. D-dimer (338 +/- 192 vs. 190 +/- 170 microg/dL, P < 0.001), TAT (4.4 +/- 2.0 vs. 1.2 +/- 0.7 ng/mL, P < 0.001), and PF 1 + 2 (1.6 +/- 0.6 vs. 0.7 +/- 0.3 nmol/L) levels were significantly higher in the critical stenosis group as compared to the noncritical stenosis group. However, fibrinogen levels were similar in both groups. The levels of TAT (r = 0.76, P < 0.001) and PF 1 + 2 (r = 0.73, P < 0.001) were correlated with the culprit lesion severity, but D-dimer and fibrinogen levels were not. Thrombolysis in myocardial infarction flow grades were also correlated with TAT (r = -0.42, P < 0.001) and PF 1 + 2 (r = -0.40, P < 0.001). The severity of culprit lesion may be associated with plasma D-dimer, TAT, and PF 1 + 2 levels in NSTE-ACS patients. These prothrombotic factors may have a role in the development of significant stenosis in the NSTE-ACS setting.

The Significance of Endothelial Heterogeneity in Thrombosis and Hemostasis

The endothelium is recognized today as a functional and dynamic component of the body that plays an important part in health and disease. This article briefly reviews the role of endothelium in thrombosis and hemostasis. There is a paradigm shift from one that regards the endothelium as one single entity to the concept that the endothelium is heterogeneous. Thrombotic complications in many disorders show a predilection to specific locations, despite the fact that a hypercoagulable state affects the entire body. Likewise, bleeding is more commonly encountered in certain anatomical locations than in others. Recent observations of the heterogeneous distribution of coagulation and fibrinolytic factors in the endothelium and the adaptation of the endothelium to various stimuli may provide an explanation for the diverse phenotypes. Recognition of this changing paradigm is helpful to for the diagnosis and management of bleeding and thrombotic complications. It also helps in the understanding of the pathogenesis of many bleeding and thrombotic disorders, and in the development of new drug designs for site-specific therapy.

Thrombotic and Fibrinolytic Factors in Acute Coronary Syndrome

Thrombotic and Fibrinolytic Factors in Acute Coronary Syndrome

Significance of factors of coagulation and fibrinolysis in progression of lung cancer

To clarify the significance of factors of coagulation and fibrinolysis in tumor progression, we measured levels of D-Dimer, Thrombin-Anti-Thrombin III complex (TAT), and Plasmin-alpha 2-Anti-Plasmin complex (PAP) in 55 patients with primary lung cancer, and studied the relationship between these parameters and clinical TNM stage. D-Dimer, TAT and PAP increased in parallel with progression of primary tumor and distant metastasis, whereas there was no significant relationship between the progression of nodal involvement and these factors. In 19 patients, we investigated changes of D-Dimer, PAP and TAT during chemotherapy. These parameters decreased in the partial response group and minor response group, whereas they increased in the progressive disease group. These data suggest that D-Dimer, PAP and TAT determination is useful for evaluation of disorders of coagulation and fibrinolysis related to tumor progression or remission in patients with lung cancer.

Age-related changes in fibrin networks and platelets of individuals over 75: a scanning electron microscopy study showing “thrombotic preparedness”

During aging, changes in vasculature, haemostasis and endothelium, including alterations of platelets, coagulation and fibrinolytic factors, occur. Research has also reported that healthy, aged individuals have heightened coagulation enzyme activity, accompanied by signs of enhanced formation of fibrin and secondary hyperfibrinolysis. It is now believed that the impaired fibrinolytic potential in old age results in a condition that has previously been described as a systemic state of "thrombotic preparedness". This state is far out of proportion to the physiological needs of the person. In the current research we investigate whether this apparent changed thrombotic profile in healthy aged individuals (over the age of 75), is evident in their platelet and fibrin network ultrastructure, when compared to healthy individuals under 25 years. The main differences among young and older individuals were found in the fibrin network ultrastructure. It is concluded that with age, major fibers seem to become thinner and more sparsely arranged and that minor, thin fibers dominate it the coagulum, forming a fine netlike structure. At irregular intervals in the coagulum, thicker, fibrin fiber lattices are present; this is not found in healthy individuals. This might be due to the previously suggested enhanced fibrin formation and heightened coagulation enzyme activity. Here we therefore provide ultrastructural evidence for the thrombotic preparedness previously suggested after studying biochemistry of fibrinolysis and coagulation factors in the elderly.

Long-term stability of fibrinolytic factors stored at -80 °C

Introduction Blood samples in epidemiological studies are often stored for several years and analysed at different occasions. The reagent kits are continually modified for better precision and accuracy. Our hypothesis was that epidemiological studies are affected by long-term storage and/or modifications of reagent kits. Materials and Methods Plasma samples stored at -80 °C from two populations were used: A case-referent study with samples collected from 1985 to 2000 and analysed 2005 (n = 1598) were used to study influence of long-term storage. A cross-sectional study analysed 1990 (n = 1558) and re-analysed 2001 (n = 78) and 2005 (n = 828) was used to study influence of reagent kit modifications. Fibrinolytic analyses included immunoassays of tPA, PAI-1 and tPA-PAI-1 complex and chromogenic substrate assays of the activities of tPA and PAI-1. Results Long-term storage for a median time of 11.6 years (range 5 to 20) showed an effect of time on tPA antigen R 2 = 0.01, PAI-1 antigen R 2 = 0.01 and tPA-PAI-1 complex R 2 = 0.02. Modifications in reagent kits affected the levels of fibrinolytic factors; for tPA antigen the slope coefficients were between 0.72 and 0.95 (R 2 0.47 - 0.75), whereas tPA activity showed an agreement with slope coefficients 1.06 to 1.09 (R 2 0.67 - 0.93). Conclusions This study showed that long-term storage affects fibrinolytic variables to a negligible extent, but modifications in reagent kits introduced an element of bias. We conclude that analysis of samples on a single occasion is preferable to multiple occasions, as storage has negligible effect.

The role of fibrinolytic factors in atherosclerosis − findings in gene altered mice −

The role of fibrinolytic factors in atherosclerosis − findings in gene altered mice −

Acute Myeloid Leukemia with Mutated NPM1 Presenting with Life-Threatening, Either Arterial or Venous, Thromboembolism: a Report of 4 Cases.

Abstract 4135Acute myeloid leukemia (AML) expressing mutated NPM1 gene and cytoplasmic nucleophosmin (NPMc+ AML) [Falini B et al, NEJM 2005;352:254-266] is a new entity of WHO classification that shows distinctive biological and clinical features. AML with mutated NPM1 usually presents with a high white blood cell count; the bone marrow biopsy is usually markedly hypercellular and leukemic cells frequently show myelomonocytic or monocytic features, with dysplasia and involvement of two or more cell lineages in about 25% of cases. Lack, or low expression, of CD34 in over 90% of cases is the most distinctive immunophenotypic feature of NPM1-mutated AML and is independent of leukemic cell maturation. NPM1 gene mutation without concomitant FLT3-ITD identify a subgroup of AML patients with a favorable prognosis and has been associated with an approximately 50-60% probability of survival at 5 years in younger patients. Here we report 4 out of 41 (10%) patients, admitted at our Hospital in the last year, with new-diagnosed AML with mutated NPM1 presenting with life-threatening thromboembolic (either arterial or venous) events. The main characteristics of these patients are summarized in Table 1. The patients had neither personal nor family history concerning thromboembolism. Hyperleukocytosis was a common feature of the vast majority of NPM1-mutated AML patients at diagnosis. Immunophenotypic analysis did not show a peculiar phenotype in these patients.Table 1Characteristics of patients with NPM1-mutated AML and thrombosis.Case report noAgeSex (M/F)FAB subtypeWBC/mmcType of thrombosisSite of thrombosis141FM114970arterialAnterior interventricular branch of left coronary artery256MM493990arterialexternal iliac and femoral (right limb)363MM2113000deep venousgreat saphenous veins (bilateral)473FM4190000deep venousiliac and femoralIn two patients (cases 1 and 2), the arterial thromboembolic event (acute myocardial infarction and acute ischemia of right lower limb, respectively) presented about one month before diagnosis of leukemia. In the other 2 patients (cases 3 and 4), deep venous thromboembolism was concomitant with the diagnosis of leukemia. One patient (case 4), who could not initiate chemotherapy for severe concomitant renal failure, died few days after diagnosis. The other patients recovered from the acute event and upon diagnosis of leukemia were promptly treated with standard polychemotherapy which allowed to obtain complete hematological remission associated with complete resolution of the thromboembolic event. The clinical course after chemotherapeutic treatment of the patients outlines the importance and life saving role of early chemotherapy even under adverse circumstances. The pathogenesis of thromboembolic disease in hematological malignancies is complex and multifactorial: tumor cell-derived procoagulant, fibrinolytic or proteolytic factors and inflammatory cytokines affect clotting activation. Other important factors include infectious complications and hyperleukocytosis. However, large vessel thrombosis is a very rare clinical presentation. Our report of severe thromboembolic events at presentation in AML with mutated NPM1 suggests some still unidentified biological features of this leukemia which we are currently investigating. Disclosures:No relevant conflicts of interest to declare.

Polyelectrolyte multilayer films allow seeded human progenitor-derived endothelial cells to remain functional under shear stress in vitro

There is considerable interest in making multilayer films for various applications, among which are cell contacting biomaterials, allowing new opportunities to prepare functionalized biomaterials. In this study we have explored the capability of poly(sodium-4-styrene sulfonate)/poly(allylamine hydrochloride) polyelectrolyte multilayer films (PMFs) as functional coatings for human progenitor-derived endothelial cells (PDECs), since the latter are a potential source of endothelial-type cells to be used in bioartificial vascular substitutes. We performed investigations with PDECs derived from peripheral blood and characterized as endothelial cells. After forming a confluent monolayer on PMFs they were exposed to laminar pulsatile physiological shear stress. We investigated whether PDECs were able to withstand shear stress and to respond at the mRNA (microarray analysis) and protein levels (thrombomodulin and tissue factor functional activity), in comparison with collagen I and fibrin glue used as controls. After shear stress the PDECs remained spread on the substrates, with a resulting increase in the number of expressed genes. Considering the functional significance of our findings for the regulation of coagulation and fibrinolytic factors, mRNA tissue plasminogen activator and thrombomodulin, profibrinolytic and thrombin inhibiting respectively, were overexpressed in PDECs after 6 h shear stress. von Willebrand factor showed down-regulation, while tissue factor was up-regulated. We can speculate that PMFs could favour anti-thrombogenic activity by PDECs because activated protein C generation, measuring thrombomodulin activity, was particularly high on PMFs, but unchanged after 6 h shear stress. Thus, PMFs could represent suitable coatings able to provide functional surfaces for endothelialization with PDECs.

Abstract 5483: The Inflammatory Protein Complement C3 is a Novel Substrate for Factor XIII and Impairs Fibrin Clot Lysis

Introduction: Inflammation is fundamentally important in the pathogenesis of cardiovascular disease (CVD) and increasing evidence supports a functional role for complement C3. Using a functional proteomics approach we have identified zymogen and activated C3 in perfused solubilized clots, suggesting C3 influences thrombus formation. Hypothesis: In this study we assessed the hypothesis that complement C3 interacts with coagulation and fibrinolytic factors to influence thrombosis. Methods and Results: Analysis of 123 paired plasma and serum samples revealed that 24.8% (SD 7.6) of plasma C3 was incorporated into the clot. To explore the mechanism of incorporation we investigated binding interactions between C3, fibrin and FXIII using ELISA based binding assays and surface plasmon resonance and found that C3 bound to immobilized fibrinogen and FXIII in a concentration dependent manner. Further analysis of the interactions between C3 and FXIII demonstrated that activated FXIII (FXIIIa) incorporated a known FXIIIa substrate, 5-(biotinamido)pentylamine, into immobilized C3 in a concentration dependent manner and FXIIIa also induced the formation of high-molecular weight C3 polymers, indicating that C3 is a FXIII substrate. Furthermore, FXIIIa incorporated plasma C3 into immobilized fibrin and Western blot analysis of clots formed from purified fibrinogen and C3 indicated high molecular weight bands that cross-reacted with specific antibodies against C3 and fibrinogen, suggesting that C3 is cross-linked to fibrin alpha chains. In turbidimetric assays using purified proteins C3 prolonged fibrin clot lysis times in a concentration dependent manner and Western blot analysis of lysed clots indicated that C3 was cleaved by plasmin, suggesting impaired fibrinolysis is due to substrate competition for plasmin. Increased plasma C3 concentration was significantly associated with increased ex vivo plasma clot density and prolonged fibrinolysis times, after adjusting for fibrinogen concentrations, to support our in vitro results. In conclusion, taken together these data indicate that complement C3 influences key processes involved in fibrin formation and fibrinolysis supporting a role for C3 in cardiovascular thrombosis.

A novel ultrasound-based method to evaluate hemostatic function of whole blood

Background Unregulated hemostasis represents a leading cause of mortality and morbidity in the developed world. Being able to recognize and quantify defects of the hemostatic process is critical to reduce mortality and implement appropriate treatment. Methods We describe a novel ultrasound-based technology, named sonorheometry, which can assess hemostasis function from a small sample of blood. Sonorheometry uses the phenomenon of acoustic radiation force to measure the dynamic changes in blood viscoelasticity during clot formation and clot dissolution. We performed in vitro experiments using whole blood samples of 1 ml to demonstrate that sonorheometry is indicative of hemostatic functions that depend on plasma coagulation factors, platelets, and plasma fibrinolytic factors. Results Sonorheometry measurements show titration effects to compounds known to alter the coagulation factors (GPRP peptide, 0 to 8 mmol/l), platelets (abciximab, 0 to 12 μg/ml), and fibrinolytic factors (urokinase, 0 to 200 U). Repeated measurements of blood samples from the same subjects yielded reproducibility errors on the order of 5%. Conclusions These data indicate that sonorheometry accurately quantifies the functional role of the components of hemostasis in vitro.

The effect of short-term aerobic training on coagulation and fibrinolytic factors in sedentary healthy postmenopausal women

ObjectiveThe purpose of this study was to assess the effect of short-term aerobic training on the fibrinolytic and coagulative factors in postmenopausal women. Study designTwenty volunteer sedentary healthy postmenopausal women (48–53 years), who entered the menopause naturally, were divided randomly into two groups: training (n=10) and control (n=10). Methods and main outcome measuresTraining consisted of 10 sessions of submaximal aerobic cycling, 35min for each session (5min warm-up, 25min aerobic training with 70% HRmax, 5min active and 15min passive recovery), 3 times a week. Coagulation and fibrinolytic factors were assessed both before and after aerobic program in both groups. ResultsFibrinogen, von Willbrand factor (vWF-Ag) antigen, plasminogen activator inhibitor-1 activity (PAI-1:Ac) and antigen (PAI-1:Ag) showed significant reduction after 10 sessions in the training group (P<0.05). Also after training, prothrombin time (PT), partial thromboplastin time (PTT), tissue plasminogen activator activity (tPA:Ac) and antigen (tPA:Ag) increased (P<0.05). ConclusionIt was concluded that fibrinolytic activity on postmenopausal women could be improved by a 3-week regular submaximal training program. These changes on the hemostatic factors suggest that short-term aerobic training may prevent the decline in fibrinolytic function observed in sedentary postmenopausal women.

Impact of acute cellular rejection on coagulation and fibrinolysis biomarkers within the immediate post-operative period in pediatric liver transplantation

We studied restoration of the coagulation and fibrinolysis system in pediatric patients following liver transplantation and biomarkers of blood coagulation and fibrinolysis for suspecting the occurrence of acute cellular rejection. Coagulation activity recovered rapidly within two days following transplantation, but it took approximately 21-28 days for full recovery of the coagulation and fibrinolysis factors synthesized in the liver. PAI-1 levels were significantly higher in patients at the time of acute cellular rejection compared with levels after control of AR, and levels on days 14 and 28 in patients without AR. Plasma protein C and plasminogen levels at the time of rejection were significantly lower than those on day 14 in patients without AR. Statistical analysis suggested that an increase in plasma PAI-1 at a single time point in the post-operative period is a reliable marker among the coagulation and fibrinolysis factors for suspecting the occurrence of acute cellular rejection. These data suggested that appropriate anticoagulation may be required for 14 days after liver transplantation in order to avoid vascular complications and measurement of plasma PAI-1 levels may be useful for suspecting the occurrence of acute cellular rejection in pediatric patients following liver transplantation.

A possible strategy for the prevention and preventive therapy of age-related macular degeneration based on recent pathophysiological and clinical observations

Abstract In the genesis and later development of age-related macular degeneration (AMD), endothelial dysfunction (ED) has a crucial role. Various medicines (ACE inhibitors, AR blockers, statins, acetylsalicylic acid, trimetazidine, and third generation beta blockers) exert a beneficial effect on endothelial dysfunction or its consequential functional, structural and metabolic disorders. The beneficial effect of a favourable influence on and successful treatment of ED in patients with chronic vascular and cardiovascular diseases has become evidence now. In ED induced by oxidative stress (OS) ACE inhibitors, AR blockers and statins regenerate the lost balance between vasoconstrictors and vasodilators, growth factors and their inhibitors, pro-inflammatory and anti-inflammatory agents, as well as pro-thrombotic and fibrinolytic factors. They inhibit the development of OS and the evolution of its harmful effects. In addition, the AT1-receptor blocker telmisartan, with its peroxisome proliferator-activated rece...

Haemostatic and fibrinolytic factors in men with a small abdominal aortic aneurysm

: The presence of an abdominal aortic aneurysm (AAA) independently predicts cardiovascular disease (CVD) and its complications. Levels of plasma markers of fibrin turnover are raised in men with a large AAA (at least 5.5 cm) and predict CVD risk in healthy subjects. This study examined fibrin turnover in men with a small AAA. : Seventy-five men with a small AAA (30-55 mm) were compared with 90 controls matched for age, sex and race. Haemostatic and fibrinolytic parameters were assessed. : Men with a small AAA had higher mean levels of fibrinogen (2.92 versus 2.59 g/l; P = 0.019), thrombin-antithrombin (TAT) complex (4.57 versus 1.89 ng/ml; P < 0.001), prothrombin F1 + 2 (1.13 versus 0.82 ng/ml; P = 0.004) and D-dimer (346.7 versus 120.2 ng/ml; P < 0.001). All markers correlated with maximum aortic diameter determined by ultrasonography. On multivariable regression the association between presence of an AAA and fibrinogen, TAT complex, prothrombin F1 + 2 and D-dimer levels remained significant after adjustment for confounding influences. : Fibrin turnover was increased in these men with a small AAA, independently of concomitant CVD, conventional risk factors and inflammatory markers. Enhanced fibrin turnover may contribute to the risk of cardiac complications in this group.

Heritability of Clot Formation

The development of occlusive arterial and venous disease is contingent on the formation of a fibrin mesh that occurs following tissue damage and activation of the coagulation system. Clinical evidence indicates that fibrin structure and function are important determinants of cardiovascular risk, and the difference between clots formed from plasma and from purified fibrinogen highlights the importance of plasma factors in determining final clot structure. Twin, family, and case-control studies indicate there is a significant genetic contribution to variance in coagulation and fibrinolytic factors that may influence clot structure. Additionally, studies indicate a smaller but significant genetic contribution to fibrin structure, with a larger component provided by the environmental contribution. Future studies of the influence of post-translational modifications to fibrin(ogen) and other factors involved in clot formation may provide important insights into thrombotic disease mechanisms.

Relationship between elevated cerebrospinal fluid levels of plasminogen activator inhibitor 1 and neuronal destruction in patients with neuropsychiatric systemic lupus erythematosus

A homeostatic imbalance between coagulation and fibrinolysis might occur intrathecally in neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no published data on levels of fibrinolytic factors in the cerebrospinal fluid (CSF) of patients with NPSLE. The present study was undertaken to assess CSF levels of fibrinolytic molecules, including urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), D-dimer, and plasminogen activator inhibitor 1 (PAI-1), in SLE patients with clinically verified neuropsychiatric involvement and to compare these levels with those in SLE patients without neuropsychiatric involvement and in healthy subjects. Levels of uPA, tPA, and PAI-1 were assessed in CSF from 94 patients with SLE (33 who had NPSLE, 56 who did not have NPSLE, and 5 who were positive for antiphospholipid antibody [not included in the NPSLE or non-NPSLE group]) and from 53 age-matched controls. Patients were evaluated clinically, with magnetic resonance imaging of the brain, analyses of neuronal/glial degradation products in CSF, and neuropsychiatric testing. In the group of patients with NPSLE, intrathecal PAI-1 levels were significantly elevated compared with levels in SLE patients without overt neuropsychiatric involvement (P < 0.05) and in healthy controls (P < 0.001). In contrast, intrathecal levels of uPA did not differ significantly. Intrathecal levels of PAI-1 correlated significantly with CSF levels of interleukin-6 (IL-6) (r = 0.34, P < 0.001) and IL-8 (r = 0.33, P < 0.001). Importantly, increased PAI-1 and D-dimer levels were observed in SLE patients who had pathologically elevated levels of glial fibrillary acidic protein, neurofilament triplet protein, and tau protein in CSF. Intrathecal release of PAI-1 is increased in patients with NPSLE. This results in impaired fibrinolysis, which might contribute to neuronal and astrocytic damage in NPSLE.

Prothrombin fragment 1 + 2 is associated with intima media thickness of the carotid artery in patients with myocardial infarction

Background and aim Previous studies have shown that a decreased fibrinolytic activity or a hyperactivated coagulation system increase the risk of myocardial infarction. The aim of this study was to investigate the relationship between the presence of atherosclerotic lesions and coagulation and fibrinolysis factors and high sensitivity CRP (hs-CRP) in patients with myocardial infarction. Methods In a cross-sectional study, 123 patients, aged 31-80 years, with a history of previous myocardial infarction were examined with B-mode ultrasound of the common carotid artery. Blood samples were collected for measurements of fibrinogen, plasminogen activator inhibitor-1 activity (PAI-1), von Willebrand factor (vWF), prothrombin fragment 1 + 2 and hs-CRP. Results Prothrombin fragment 1 + 2 and hs-CRP were significantly (p < 0. 05) and positively associated with common carotid artery intima media thickness (IMT). PAI-1 was significantly (p < 0.05) and negatively associated with IMT. IMT was also significantly associated with systolic blood pressure and age. When IMT was used as an dependent variable and systolic blood pressure, age, PAI-1 and prothrombin fragment 1 + 2 were used as independent variables in the multiple stepwise regression analysis a significant and independent relationship was observed between IMT and systolic blood pressure and age (p < 0.05). Conclusion The levels of prothrombin fragment 1 + 2 and hs-CRP are associated with intima media thickness in the common carotid artery in patients with previous history of myocardial infarction.

Effects Of Kaatsu Training On Haemostasis In Healthy Subjects

The KAATSU training is performed under the reduction of muscle blood flow by a specially-designed belt (KAATSU belt), which induces blood pooling in capacitance vessels by restricting venous return. However, no prior studies have examined the effects of KAATSU training on haemostasis. PURPOSE: We investigated acute effects of KAATSU training on haemostasis including fibrinolytic responses under several conditions. in healthy subjects. METHODS: Two protocols have been performed. (1) 6 healthy men (mean age, 48 ± 5 yr) performed KAATSU (160 mmHg) of both thighs for 15 minutes and then KAASTU training combined with low-intensity leg and foot aerobic exercises for ∼10 minutes in hypobaric chamber, which mimics 8000 feet in airflight. (2) Another 7 men (mean age, 30 ± 4 yr) performed leg press exercises (30 % 1 RM) with and without KAATSU of both thighs 24 h after bed rest. Blood samples were taken at rest, immediately after KAATSU, and exercises with or without KAATSU, and after exercise. For the investigation of blood fibrinolysis, determinations of tissue-type plasminogen activator (tPA) activity or antigen, plasminogen activator inhibitor (PAI)-1 activity or antigen, fibrin degradation product (FDP) and D-dimer were used. Prothrombin time (PT) and platelet counts were also measured. RESULTS: (1) In hypobaric chamber, KAATSU by itself significantly increased tPA activity, while PAI-1 activity was unchanged. Furthermore, immediately after the exercise, tPA activity increased significantly. (2) During the exercises combined with KAATSU 24 h after bed rest, tPA antigen significantly increased, compared with control exercises, but PAI-1 antigen was unchanged. In both cases, KAATSU training did not induce fibrin formation as assessed by fibrin D-dimer and FDP. CONCLUSIONS: This study indicates that potentially favorable changes occur in fibrinolytic factors after KAATSU and KAATSU training in healthy subjects.