Şerafettin Kirazli

Increased plasma levels of soluble selectins in patients with unstable angina

BACKGROUND Inflammation plays an important role in the pathogenesis of unstable angina. Adhesion molecules, such as selectins, mediate the interactions between leukocytes, platelets and endothelial cells during inflammation and thrombogenesis. HYPOTHESIS The purpose of this study was to determine whether soluble E-selectin, P-selectin and L-selectin levels are increased in patients with unstable angina (UA). METHODS Soluble E-, P- and L-selectin levels were measured by enzyme-linked immunoassay in the peripheral blood of 23 patients with UA, 26 patients with stable angina (SA) and 15 control patients with angiographically normal coronary arteries. RESULTS Soluble E-selectin levels were significantly higher in patients with UA (45+/-11 ng/ml) than in controls (30+/-8 ng/ml, P<0.001), or patients with SA (34+/-8 ng/ml, P=0.001). Similarly, plasma levels of P- and L-selectin were significantly higher in patients with UA (427+/-144 and 772+/-160 ng/ml, respectively) than in patients with SA (278+/-79 and 643+/-94 ng/ml, respectively, P<0.005 vs. UA for both), or control patients (189+/-43 and 601+/-126 ng/ml, respectively, P=0.001 vs. UA for both). CONCLUSIONS Plasma levels of soluble selectins were increased in patients with UA compared with patients with SA or patients without angiographically visible coronary artery disease. Measurements of these adhesion molecules may be helpful as non-invasive markers of coronary plaque destabilization in UA.

Unchanged global fibrinolytic capacity despite increased factor VIIa activity in Behçet's disease: evidence of a prethrombotic state

Abstract.The aim of this study was to evaluate coagulation and fibrinolytic systems in Behçets disease (BD). Accordingly, various parameters of the coagulation and fibrinolytic systems were investigated in 39 patients with BD and 31 age- and sex-matched healthy volunteers as the control group. Seven of these patients with BD had histories of thrombotic complication. Three were found to have decreased protein S activity, and one patient had diminished protein C activity. Each of those patients had experienced a thromboembolic event. Activated protein C resistance was present in two patients, one of whom had had a thromboembolic episode. Activated FVII (FVIIa), fibrinogen, and cholesterol levels were significantly higher in patients with BD than in the control group. In the patient group, plasma FVIIa level was inversely correlated with age. Plasma global fibrinolytic capacity (GFC) did not differ between the patients and control group. No statistically significant difference was found in the GFC and FVIIa levels between patients with and without histories of thrombosis. Although the coagulation system was activated in vivo in patients with BD, there was no reactive activation in the fibrinolytic system to counteract the activated coagulation system. These findings suggest a relative hypofibrinolytic state in BD.

Thrombopoietin, interleukin-6, and P-selectin at diagnosis and during post-steroid recovery period of patients with autoimmune thrombocytopenic purpura

Abstract Plasma concentrations of the most potent megakaryocytopoietic cytokines, thrombopoietin (TPO) and interleukin-6 (IL-6), and the platelet activation marker P-selectin were evaluated in 24 patients with autoimmune thrombocytopenic purpura (ATP) who responded to conventional steroid treatment, at diagnosis and after steroid-induced recovery. Baseline TPO concentration (median [interquartile range]= 0 [17.52] pg/ml) was significantly decreased and IL-6 (38 [19.75] pg/ml) and P-selectin (485 [393.75] ng/ml) were significantly elevated compared with healthy subjects (100 [68] pg/ml, 8 [7] pg/ml and 166 [69] ng/ml, respectively). Following steroid treatment, all values approached normal, i.e., TPO (20 [18.75] pg/ml) was increased and IL-6 (19.5 [13] pg/ml) and P-selectin (248 [172.5] ng/ml) were decreased, significantly. The decrease of TPO in ATP is suggested to occur due to increased megakaryocyte mass and, consequently, TPO clearance. The non-lineage-specific cytokine IL-6 may be elevated to compensate for megakaryocytopoiesis/thrombopoiesis. The elevation of P-selectin may reflect compensatory platelet hyperactivation; however, this molecule also might be a marker of platelet destruction.

Serum beta 2-microglobulin reflects disease activity in Behçet's disease.

Abstract. Behçets disease (BD) is a systemic remitting vasculitis characterized by orogenital ulceration and uveitis. The disease is not associated with specific laboratory abnormalities. Hence, the activity of BD is generally assessed by clinical findings and – to some extent – by nonspecific markers of inflammation. This study was performed to investigate the relative efficiency of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum amyloid A protein (SAA), and beta 2-microglobulin (beta 2-m) levels as markers of disease activity in patients with BD. The study population consisted of 20 patients with active BD, 23 patients with inactive BD, and 27 healthy adults serving as the control group. Serum beta 2-m, SAA, ESR, and CRP levels of patients with BD were found to be significantly higher than those in the healthy control group. They were also higher in patients with active disease than in those in remission and controls. The levels of SAA, ESR, and CRP in inactive patients were also significantly higher than the controls. No statistically significant difference was noted between beta 2-m levels of patients with inactive BD and healthy controls. Serum beta 2-m levels can be regarded as a more discriminative marker of activation in BD. The high diagnostic value of SAA levels indicate that it can also be accepted as a marker of disease activity in BD.

Paget-Schroetter Syndrome Associated with FV:Q506 and Prothrombin 20210A A Case Report

Effort thrombosis of the axillary-subclavian vein (Paget-Schroetter syndrome) develops usually secondary to heavy arm exertion. An underlying chronic venous compressive anomaly at the thoracic outlet or intimal damage of the axillary vein following forceful hyperabduction, external rotation of the shoulder joint has been proposed to explain the pathophysiology of this thrombosis. This condition is usually not attributed to an under lying hypercoagulability such as deficiency of natural coagulation inhibitors. Here, the authors present a case with thrombosis of the axillary-subclavian vein following an effort, with factor V Leiden and prothrombin 20210A mutations. Both factor V Leiden and the genetic variant in the prothrombin gene have been shown to confer an increased risk for venous thrombosis. Although rare, effort thrombosis may develop in a patient with hereditary thrombophilia, so laboratory evaluation should include the common causes of thrombosis.

Soluble Thrombomodulin and Fibrinolysis in Behçet’s Disease

Behcet’s disease is a chronic relapsing systemic vasculitis in which recurrent urogenital ulceration is a prominent feature. The precise reason underlying the thrombotic tendency in Behcet’s disease i

Decreased Protein Z Concentrations Complicating the Hypercoagulable State of Behqet's Disease

Protein Z is a vitamin-K-dependent plasma protein that serves as a cofactor for the inhibition of factor Xa. Although the precise physiologic function of protein Z is still unknown, abnornal plasma protein Z concentrations have been associated with a number of thrombotic disease states. There is the evidence of universal activation of the hemostatic system in Behqets disease (BD), which represents a hypercoagulable/prothrombotic state. Circulating protein Z levels in patients with BD were evaluated. Plasma protein Z concentrations were assayed in 24 patients with BD (male/female: 13/11, mean age 35.4 years) and in 24 healthy controls (males/females: 14/10, mean age 59.8 years). The disease duration was 10.6 years (range, 1-30 years). None of the subjects in either group had received anticoagulants within 3 weeks before the study, and none of them had liver dysfunction. Patients complicated with vascular disease were also excluded from the study. Mean plasma concentrations of protein Z were 141 ng/mL (range, 56.8-257) in healthy controls and 107.8 ng/mL (range, 21.2-202) in BD patients (p<0.05). There was a positive correlation between the disease duration and protein Z levels in the study group (p<0.05, r=0.448). Alterations of protein Z concentrations could complicate the pathobiology of the prothrombotic state of BD. Furthermore, the tendency of increment in the protein Z with the passage of time may reflect the diminution of the disease activity.

Impaired fibrinolytic capacity in rheumatic mitral stenosis with or without atrial fibrillation and nonrheumatic atrial fibrillation

Chronic atrial fibrillation (AF) has often been associated with systemic embolization, and patients with mitral stenosis (MS) have the highest thromboembolic risk. Increased risk of thromboembolism could be in part due to impaired fibrinolytic function. Global fibrinolytic capacity (GFC) is an innovative technique for evaluating the entire fibrinolytic system. The aim of our study was to evaluate fibrinolytic activity in patients with rheumatic and nonrheumatic chronic AF. To investigate fibrinolytic activity, we assessed GFC in peripheral blood samples of 32 patients with nonrheumatic AF (14 women; mean age, 56 ± 1 years), 30 patients with rheumatic MS and AF (23 women; mean age, 35 ± 9 years), and 32 patients with rheumatic MS and sinus rhythm (24 women; mean age, 36 ± 8 years). The control group comprised 30 healthy adult subjects in normal sinus rhythm. Patients with chronic AF (rheumatic and nonrheumatic) had lower GFC than did the controls (P = .0001). The rheumatic AF group also showed decreased levels of GFC compared with the nonrheumatic AF group, with the rheumatic MS and sinus rhythm group, and with controls (P = .03,P = .02,P = .0001, respectively). GFC was lower in patients with rheumatic MS and sinus rhythm than in controls (P = .003). Although there were correlations between GFC and mitral valve area, transmitral mean gradient, left atrial diameter, and mitral calcification in patients with rheumatic MS, multivariate analysis showed only transmitral gradient as an independent factor affecting GFC. Patients with AF have decreased GFC, a finding that suggests the presence of a hypofibrinolytic state. Fibrinolytic dysfunction was more pronounced in rheumatic MS patients with AF than in those with nonrheumatic AF. Moreover, patients with rheumatic MS and sinus rhythm had decreased global fibrinolytic activity. Hypofibrinolysis documented by decreased GFC can be one of the important causes of increased risk of embolism in patients with AF and rheumatic MS.

Statin Potentiates Human Platelet eNOS Activity without Enhancing eNOS mRNA and Protein Levels

Background/Aims: Experimental studies suggest an enhanced endothelial and platelet nitric oxide (NO) generation after statin treatment, possibly due to increased endothelial NO synthase (eNOS) activity and protein levels. In parallel with experimental research, statins were shown to increase the forearm blood flow independently of serum cholesterol in humans. However, it was not possible to correlate blood flow changes with eNOS levels in these studies due to limitations in obtaining arterial samples. Hence, we investigated changes in eNOS activity, mRNA and protein levels after statin treatment in human platelets, which are readily accessible unlike arteries. Methods: In vitro bleeding times were measured in 22 patients by stimulating platelets with collagen-epinephrine or collagen-ADP. To assess platelet eNOS activity, the bleeding times were also determined after incubating platelets with L-arginine. The measurements were repeated following 14 days of pravastatin (40 mg/day) treatment. Platelet-rich plasma was collected before and after statin treatment to evaluate eNOS mRNA (semiquantitative RT-PCR) and protein levels (Western blotting). Results: The basal bleeding time was prolonged by 24 ± 3% (mean ± SE) when the samples were incubated with 500 µM of L-arginine. The NOS inhibitor L-N5-(I-iminoethyl)ornithine reversed this effect, suggesting that it was mediated by NO. After statin treatment, the NO-mediated prolongation of the bleeding time with 500 µM of L-arginine was significantly potentiated (to 44 ± 10%). Despite enhanced eNOS activity, there was no significant change in platelet eNOS mRNA and protein levels after statin treatment. Conclusion: These data demonstrate that platelet eNOS activity is potentiated after statin treatment in humans in parallel with experimental studies.

Beta-Thromboglobulin and Platelet Factor 4 Levels in Pregnancy and Preeclampsia

The plasma levels of beta-thromboglobulin (BTG) and platelet factor 4 (PF-4) were measured in patients during the normal obstetric period and in preeclampsia. A significant increase was observed in the two proteins with respect to the nonpregnant control group. Both proteins increased significantly with preeclampsia and a further increment was observed with the severity of preeclampsia though no significant difference in PF-4 levels was encountered between pregnant and mildly preeclamptic women. There was no correlation between BTG, PF-4 and thrombocyte counts.