Plasminogen activator inhibitor-2 and alpha-fetoprotein in various liver disease states.
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Biomedical subjects
Publications and source records attributed to S Kirazli.
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Whilst increased plasma beta-thromboglobulin (beta TG), platelet factor 4 and thrombospondin levels are regarded as reflecting the release reaction of platelets, tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) levels represent endothelial release reaction and/or damage. In this study including 12 smokers and 9 nonsmokers, we investigated the acute and chronic effect of smoking on these parameters and antithrombin III, protein S and fibrinogen, as well. Nonsmokers were found to have somewhat higher plasma levels of beta TG, t-PA and PAI-1 than chronic smokers, and 30 minutes after smoking two cigarettes, these levels and protein S levels of nonsmokers showed more prominent increases than of chronic smokers. It is speculated that chronic exposure to cigarette smoke may cause "exhaustion" or "receptor down-regulation" of platelets and endothelial cells, resulting with diminished release reaction of platelets and endothelium in response to acute smoking.
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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.
A group of 23 children with cerebrovascular occlusion of unknown etiology were re-evaluated 6 months-2 years later. Plasma protein C levels were determined with the coagulation method and were low in 10 cases. The role of this deficiency and the necessity of this test in cerebrovascular occlusion is discussed.
Clinical observations have indicated the frequent development of thrombotic complications during diabetic ketoacidosis (DKA). This study aimed to examine whether haemostatic changes that could lead to a thrombotic tendency occur during ketoacidosis. Plasma levels of in vivo haemostatic markers reflecting activation degrees of the coagulation system, fibrinolytic system, platelets and endothelium were assayed in 34 patients with DKA, both at diagnosis and 1 week after recovery. We found coagulation system and platelet activation and endothelial injury/activation in the patients at diagnosis of DKA. Although significant improvements were observed after recovery, only platelet activity was completely normalized. Fibrinolytic activity was also increased, both at diagnosis and after recovery, compared to the control group. However, although coagulation activity was prominently increased at diagnosis compared to the recovery period, there was no change in fibrinolytic activity in the same periods; on the contrary, the fibrinolytic capacity of the endothelium was diminished at diagnosis of DKA compared to the recovery period, suggesting the presence of relative hypofibrinolysis during DKA. Indications for a role of hyperglycaemia in the emergence of haemostatic disturbances during DKA were observed.
The proteins beta-thromboglobulin, platelet factor 4 and thrombospondin are stored in platelet alpha-granules and released from the platelet by the release reaction. The assays of these proteins were studied in patients with type I diabetes mellitus (n = 30) and a healthy control group (n = 15). Platelet factor 4 and beta-thromboglobulin levels were not significantly different in both groups but thrombospondin concentrations in diabetic patients were significantly higher than those of the control group (136.6 +/- 14.2 ng/ml vs 91.2 +/- 14.3 ng/ml, P < 0.05). When the diabetic patients were divided into those with or without complications, the diabetic patients with complications (n = 11) had significantly elevated plasma thrombospondin concentrations compared with the control group (150.4 +/- 23.7 ng/ml vs 91.2 +/- 14.3 ng/ml, P < 0.05), while thrombospondin concentrations in the control group were not statistically different from the diabetic patients without complications. Plasma beta-thromboglobulin and platelet factor 4 levels were not significantly different between the diabetic and the control group. It is suggested that thrombospondin may be a convenient marker of in vivo platelet release reaction.
Atherosclerosis is more extensive and occurs earlier in diabetics compared with the general population. The pathophysiology of atherosclerosis is not fully established. We compared the activity of two blood clotting agents, activated factor VII (VIIa) and von Willebrand factor (vWF), in diabetic and non-diabetic subjects with coronary artery disease. According to clinical features, subjects were placed in one of four groups: Group I, non-insulin-dependent diabetes mellitus (NIDDM) with coronary heart disease (CAD) (n = 16); Group II, NIDDM (n = 15); Group III, CAD with no presence of diabetes (n = 17); and Group IV, healthy volunteers (n = 15). The level of factor VIIa was higher in Group I compared with all other groups, and was significantly higher in Group II compared with Group III and Group IV. Activity of vWF was higher in Group I compared with Group II, Group III and Group IV. There was no statistical difference between Group II and Group III. There was no significant correlation between concentration of blood glucose, total cholesterol or triglyceride, duration of diabetes and either factor VIIa or vWF activity. The results of this study suggest that increased activity of plasma vWF and factor VIIa may be useful markers to identify ischaemic heart disease risk in NIDDM subjects.
AIMS AND BACKGROUND: Disorders of hemostasis in patients with malignancies are based on several mechanisms, such as ability of the tumor to alter the coagulation system by producing blood clotting factors or decreasing their inhibitors by increasing fibrinolysis, and by inducing an alteration of blood vessels in relation to the state of local invasion. We investigated the fibrinolytic system marker alpha2-antiplasmin-plasmin complex (APP) and clotting system marker thrombin-antithrombin III complex (TAT) in patients with breast cancer and compare them with CA 15-3, the most well-known breast cancer antigen. METHODS: Plasma levels of APP and TAT and serum level of CA 15-3 were determined in 57 patients with breast cancer (28 in remission and 29 with active breast cancer) and 13 healthy women. RESULTS: In patients with active breast cancer, plasma APP levels were significantly elevated compared to those of other groups (P<0.05). In addition, we observed a poor but positive correlation between plasma levels of APP and those of CA 15-3 (r=0.24; P=0.038). Plasma TAT levels, which reflect the activation of thrombin, were also significantly elevated in patients with active breast cancer (P<0.01), and there was a significant correlation between CA 15-3 and TAT (r=0.24; P=0.041). CONCLUSIONS: We demonstrated that increased APP and TAT levels might reflect enhanced activation of coagulation and the fibrinolytic system in patients with active breast cancer.
Patients with immune thrombocytopenic purpura (ITP) rarely suffer life-threatening haemorrhages despite significant thrombocytopenia, probably because large numbers of hyperfunctioning platelets are present. Thrombospondin is a platelet alpha-granule protein and its plasma level may reflect platelet activation. We assessed circulating thrombospondin levels in 12 newly diagnosed ITP patients (one man; 11 women, aged 36 +/- 16 years) before they were treated for ITP. Twelve healthy people (four men; eight women, aged 31 +/- 11 years) acted as controls. Plasma thrombospondin concentrations were measured using enzyme-linked immunoassays. Thrombospondin concentrations tended to be higher, despite thrombocytopenia, in ITP patients (158.8 +/- 28.2 ng/ml) compared with controls (120.7 +/- 18.2 ng/ml). The difference was not statistically significant, but the relatively high circulating thrombospondin concentrations we observed suggest that residual platelets could be activated in ITP, thus indicating a more benign clinical course compared with aplastic thrombocytopenia.
We aimed to determine serum soluble Fas antigen (sFas) levels at various stages of hepatitis C virus (HCV)-induced liver disease, and investigate correlations between serum sFas levels and clinical, biochemical and pathologic features. Sixty-five patients were categorized into five groups: 1, chronic active hepatitis C, elevated alanine aminotransferase (ALT), HCV-polymerase chain reaction (PCR) positive; 2, responders to interferon + ribavirin therapy; 3, cirrhosis; 4, chronic hepatitis C, normal ALT, HVC-PCR positive; and 5, sustained responders. Group 6 comprised 15 control individuals. Serum sFas levels were measured by enzyme-linked immunosorbent assay. Significant differences in serum sFas levels were found between the following groups: 1 and 2; 1 and 3; 1 and 4; 1 and 6; and 3 and 6. Serum sFas levels did not correlate with ALT, histological activity or HCV-PCR positivity within group 1. Serum sFas levels appear to increase in advanced stages of HCV-induced liver disease, as a result of host-related immunological factors.
In immune thrombocytopaenic purpura (ITP), phagocytic cells prematurely destroy platelets opsonized by anti-platelet auto-antibodies, while residual platelets rescued from these autoimmune attacks are hyperfunctioning. The exact pathobiological basis of this phenomenon is unknown. Protein C inhibitor (PCI), a platelet alpha-granule pro-coagulant molecule, is released on activation of platelets. Serum amyloid A (SAA; an acute phase protein), however, inhibits platelet aggregation and modulates platelet adhesion. We aimed to assess circulating soluble plasma PCI and SAA concentrations in 17 patients with newly diagnosed ITP and ten healthy volunteers. Plasma PCI concentrations tended to be higher in ITP patients, despite absolute thrombocytopaenia, than in normal controls. SAA levels were significantly higher in ITP patients compared with the control group. We conclude that secretion of the alpha-granule PCI content of platelets could result from platelet activation, and that PCI may be the link between platelet microparticles and haemostatically active ITP platelets. Increased concentrations of SAA and PCI may interfere with the disordered and compensatory pro-coagulant mechanisms of ITP.
The vasoactive products of uncontrolled protease activity can play an important role in the pathogenesis of respiratory distress syndrome in newborn infants. In this study alpha-2-macroglobulin, which has antiproteolytic activity, was studied in the first few hours of life in preterm infants with and without respiratory distress syndrome. Mean plasma alpha-2-macroglobulin levels were found to be similar in both groups. These findings implicated that alpha-2-macroglobulin has no significant role in the pathogenesis of respiratory distress syndrome.
In this study, protein C (PC), protein S (PS), heparin cofactor II (HCFII), prothrombin fragment 1+2(PF1,2), thrombin-antithrombin III complex (TAT), von Willebrand factor (vWF) and thrombomodulin (TM) were investigated in 13 patients with beta thalassemia intermedia (TI) not requiring transfusion, six patients with sickle cell disease (SCD), and seven patients with HbS-beta thalassemia (S-BT) who were not in crisis. These hemostatic parameters were also studied in 12 healthy children assigned as a control group. Protein C and Protein S (PC-PS) were found to be decreased in TI patients and normal in S-BT patients. PC was decreased in SCD patients. In the patients with TI and SCD, the mean PF1,2 level was elevated, whereas the TAT level was not statistically different from that of the control group. These results suggested that in patients with hemoglobinopathies: a) decreased natural anticoagulants and b) enhanced procoagulant activation have been encountered. Other unexpected and interesting results of this study are the decreased vWF and elevated HCFII levels in all three patient groups.
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OBJECTIVE: To investigate the synovial fluid levels of interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), IL-1 receptor antagonist (IL-1ra), soluble IL-2 receptor (sIL-2r) and IL-8 in patients with Behçet's disease (BD) and to compare them to levels in rheumatoid arthritis (RA), and osteoarthritis (OA). METHODS: The cytokine levels of BD (n = 14), RA (n = 15) and OA (n = 15) patients were assessed by enzyme-linked immunosorbent method. RESULTS: Median synovial IL-1 beta and TNF-alpha levels were higher in RA compared to BD and OA patients. IL-1 beta levels were also higher in BD than OA whereas TNF levels were similar in these two groups. IL-1ra and TGF-beta activity in BD were higher than OA but lower than RA. sIL-2r and IL-8 levels were increased in BD and RA in comparison to OA patients. CONCLUSION: The arthritis of BD is non-erosive and accordingly, its synovial fluid contains lower levels of cytokines primarily involved in cartilage destruction, namely IL-1 beta and TNF-alpha, than RA. IL-1ra and TGF might serve as protective factors against erosion in the inflamed joints. High synovial fluid levels of sIL-2r and IL-8 probably reflect a non-specific inflammatory process.
Increments in circulating thrombomodulin levels reflect endothelial cell injury. Thrombomodulin can also be synthesized by several inflammatory cells including monocytes, neutrophils, and thrombomodulin itself can modulate the inflammatory response. In this study, we assessed circulating thrombomodulin concentrations in patients with familial Mediterranean fever (FMF). Twenty-five patients with FMF (F/M: 14/11) (mean age: 31.1 +/- 9.7 years) and 25 healthy controls (F/M: 13/12) (mean age: 34.6 +/- 7.0 years) were involved in the study. Thrombomodulin levels were measured by commercially available enzyme-linked immunosorbant assay (ELISA) (Immunoassay of thrombomodulin Diagnostica Stago, Asnieres-Sur-Seine, France). Twenty of the patients were in attack-free period and the remaining five had been during acute FMF attacks. Thrombomodulin levels were higher in the study group (20.9 +/- 12.1 ng/ml) than healthy controls (14.1 +/- 8.4 ng/ml) (p < 0.05). Circulating thrombomodulin levels were also higher in attack-free FMF patients (22.4 +/- 12.9 ng/ml) than controls. This study disclosed for the first time significantly higher increments in the circulating levels of thrombomodulin in FMF. This observation could be a consequence of injured endothelium and/or activated inflammatory cells.
The serum plasminogen status in 35 preterm infants with or without respiratory distress syndrome (RDS) was determined in the first few hours of life. Blood samples for plasminogen testing (Synthetic chromogenic substrate method; Stachorm PLG. Diagnostica Stago) were obtained from a peripheral vein within six hours after birth. Among 35 infants, 20 infants who were in stable clinical condition served as the control group. Fifteen developed RDS with clinical, laboratory and radiological findings. The mean plasma plasminogen levels were found to be similar in the two groups (p > 0.05 by Mann-Whitney U test). These findings are discussed along with our previous findings showing normal tissue plasminogen activator (tPA) but lower D-dimer and higher plasminogen activator inhibitor (PAI) levels within the first few hours of life in preterm infants who later developed RDS compared to the control group.