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Biomedical subjects

I C Haznedaroğlu

Publications and source records attributed to I C Haznedaroğlu.

At least 19 recordsLinked to original sources

The plasma levels of prostanoids and plasminogen activator inhibitor-1 in primary and secondary thrombocytosis.

An elevated platelet count is a common finding in both hospitalized and ambulatory patients. Thrombosis and bleeding complications are more frequently observed in patients with clonal thrombocytosis than secondary thrombocytosis. The aim of this study was to investigate the behaviors of plasminogen activator inhibitor type 1 (PAI-1), the inhibitor of fibrinolysis; and thromboxane A2 and 6-keto-PGF1 alpha, the products of endoperoxides, in 16 patients affected with clonal thrombocytemia as compared with 16 patients with reactive thrombocytosis and 15 normal controls. In the clonal thrombocytemia group, plasma levels of PAI-1 antigen and activity were significantly higher than both reactive thrombocytosis and control group. Plasma levels of 6-keto-PGF1alpha were significantly higher in the clonal thrombocytemia group than the other two groups and also higher in the reactive thrombocytosis group than the control group, which was also significant. This study confirms that arachidonate metabolism is frequently deranged in patients with thrombocytosis and hypofibrinolysis due to increased PAI-1 plasma levels as shown in the clonal thrombocytosis group. This may explain the thrombotic tendency in myeloproliferative disorders.

Adolescent↗

Plasma basic fibroblast growth factor and bone marrow fibrosis in clonal myeloproliferative disorders.

Basic fibroblast growth factor (bFGF) is an important growth factor involved in clonal hematopoietic expansion, neoangiogenesis, and bone marrow fibrosis, all of which are important pathobiologic features of clonal chronic myeloproliferative disorders (CMPD) and myelodysplastic syndromes (MDS). The aim of this study was to assess circulating bFGF concentrations in patients with CMPD and MDS with respect to the presence of bone marrow fibrosis in histopathologic examination. The study group comprised 18 patients with CMPD (six female, 12 male; median age 50 years), seven patients with MDS (one female, six male; median age 66 years) and 10 healthy adults as controls (four female, six male; median age 29 years). CMPD group included six chronic myelogenous leukemia (CML), seven essential thrombocythemia (ET), three polycythemia vera (PV), two agnogenic myeloid metaplasia (AMM). All seven MDS patients were the FAB subtype of refractory anemia (RA). Bone marrow biopsy sections stained with hematoxylin and eosin (H & E) and for reticulin were examined for the presence of fibrosis. The median plasma bFGF level was 18.2 pg/ml (interquartile range, IQR: 15.2-26.7) in patients with CMPD, 18.0 pg/ml (IQR: 15.8-26.4) in patients with MDS, 13.6 pg/ml (IQR: 9.9-20.0) in the control group. The bFGF levels were significantly higher in patients with CMPD in comparison with the healthy control group (P = 0.031). Circulating bFGF tended to be significantly lower in relation to the development of marrow fibrosis (P = 0.028). The complicated interactions of bFGF and fibrosis in the context of CMPD may be either 'cause' or 'effect'. The bFGF might represent an important link between angiogenesis, fibrosis, and clonal neoplastic hematopoiesis during the development of CMPD.

Adult↗

The predictability of factor V Leiden (FV:Q(506)) gene mutation via clotting-based diagnosis of activated protein C resistance.

After the discovery of activated protein C resistance (APCR) due to factor V Leiden mutation and the causal relationship of the phenomenon with clinical thromboembolism, a wide variety of functional clotting-based assays were developed for testing of APCR in relation to the specific DNA-based analysis of FV:Q(506) Leiden. The aim of this study is to assess a clotting-based APCR assay using procoagulant crotalidae snake venom with respect to the sensitivity, specificity, and predictability for the presence of the factor V Leiden mutation. APCR testing and factor V DNA analyses have been performed concurrently on 319 patient specimens. APCR values of the patients with homozygous factor V Leiden mutation (70.4+/-13.5 s) were significantly lower (p<0.001) in comparison to the subjects with the heterozygous mutation (87.6+/-13.4 s). The assay is highly sensitive (98.7%) and specific (91.9%) for the screening of factor V Leiden mutation. The sensitivity and specificity of the APCR testing reached to 100% below the cut-off value of 120 s among the patients with homozygous factor V Leiden mutation. Therefore, this method could help the desired effective optimal screening strategy for the laboratory search of hereditary thrombophilia focusing on the diagnosis of APCR due to FV:Q(506).

Activated Protein C Resistance↗

Bloodstream thrombopoietin in rheumatoid arthritis with thrombocytosis.

Thrombopoietin (TPO) is the major regulator of growth and differentiation of megakaryocytes. Recent studies have shown that TPO may also act as an acute-phase reactant, and it has been suggested as a component of inflammatory reactions. In this study our objective was to investigate serum TPO levels in patients with rheumatoid arthritis, a complex chronic inflammatory disorder not uncommonly associated with thrombocytosis. Bloodstream TPO concentrations were assessed in 13 RA patients with platelet counts between 450 and 650 x 10(9)/l, 10 RA patients with platelet counts >650 x 10(9)/l, 15 RA patients with normal platelet counts and 12 healthy controls. RA patients with normal platelet counts had TPO levels comparable with healthy controls. TPO concentrations in patients with mild thrombocytosis were significantly elevated, whereas patients with markedly increased thrombocyte counts had prominently decreased TPO levels. These results indicate that TPO seems to be associated with reactive thrombocytosis in RA patients with active disease. In patients with extremely increased thrombocytosis serum TPO levels might be regulated by increased platelet mass via receptor-mediated uptake and metabolism.

Adult↗

A unifying hypothesis for the renin-angiotensin system and hematopoiesis: sticking the pieces together with the JAK-STAT pathway.

JAK-STAT pathway is a recently encountered intracellular signal transduction system. The pathway is utilized by numerous cytokines, growth factors, and hormones for gene expression and a variety of biological activities. Hematopoiesis is regulated by many cytokines and growth factors that support the proliferation and differentiation of progenitor cells in the bone marrow. JAK-STAT pathway arises as the most common signalling cascade of a wide range of cytokines and/or growth factors in propagation of physiological and pathological/neoplastic hematopoiesis. On the other side, renin-angiotensin system (RAS) includes not only the classic circulating endocrine system controlling blood pressure and electrolyte homeostasis, but also tissue-specific RASs with autocrine and/or paracrine functions. Preliminary data suggest the involvement of the RAS components in normal and pathologic hematopoiesis, although the precise mechanism of action has not been elucidated yet. We have hypothesized, in this report, that JAK-STAT pathway serves as a point of crosstalk between the components of the locally present RAS in the bone marrow and hematopoiesis. Demonstration of a local RAS in the bone marrow with clarification of the postreceptor signalling events may play a consequential role not only for further clarification of normal hematopoiesis but also novel therapeutic approaches in pathologic/neoplastic conditions.

Hematopoiesis↗

Effects of angiotensin converting enzyme and angiotensin II receptor inhibition on impaired fibrinolysis in systemic hypertension.

Abnormalities in fibrinolysis have been reported in hypertension. Angiotensin converting enzyme (ACE) inhibitors have been shown to improve altered fibrinolytic balance in hypertensive patients. It has not been documented, however, whether this is due to a decrease in angiotensin II (Ang-II) generation or is a consequence of elevated local levels of bradykinin. Accordingly, the aim of this study was to determine the effects of an ACE inhibitor (perindopril) and an Ang-II receptor antagonist (losartan) on fibrinolytic kinetics. We have examined the serum levels of the plasminogen activator inhibitor type-1 (PAI-1) antigen and activity, tissue plasminogen activator (t-PA) antigen and activity, soluble thrombomodulin (sTM), and tissue factor pathway inhibitor (TFPI) before and after reaching the target blood pressure (<140/90 mm Hg) in 13 hypertensive patients receiving perindopril (mean age 40+/-11 years, 6 women, 7 men) and in 12 patients receiving losartan (mean age 38+/-9 years, 6 women, 6 men). We also compared the baseline fibrinolytic activity of hypertensive patients with that of 12 normotensive control persons (mean age 40+/-9 years, 6 women, 6 men). The mean basal plasma levels of PAI-1 antigen, PAI-1 activity, and sTM were significantly higher in the hypertensive patients than in normal controls (P<.005). The values of other analytes were similar in both groups. Increased plasma levels of PAI-1 antigen, PAI-1 activity, and sTM were reduced in patients after they were given perindopril and losartan (P<.005); the reductions in losartan-receiving group were more pronounced (P<.05). There were no significant effects on the plasma levels of t-PA antigen, t-PA activity, and TFPI in patients receiving the two therapeutic regimens (P>.05). In conclusion, chronic hypertension is associated with hypofibrinolysis. The beneficial effect of ACE inhibitors on fibrinolysis seems to be related to the blockade of Ang-II, and increased kinin activity does not appear to play a major role.

Adolescent↗

Protein Z levels in haemodialysis patients.

Protein Z (PZ) is a vitamin K-dependent protein isolated from human and bovine plasmas. Although the exact role of PZ in the haemostatic system is presently unknown, it is suggested that PZ deficiency may cause bleeding tendency. Haemostatic alterations in end-stage renal failure (ESRF) are certainly complex and involve several abnormalities in the coagulation and fibrinolytic system. In order to elucidate the detail of the haemostasis in ESRF, we aimed to investigate PZ activity in haemodialysis patients. Therefore, we compared plasma PZ levels in 10 haemodialysis patients (6 M, 4 F, mean age 36+/-11) and 10 healthy normal controls (5 M, 5 F, mean age 34+/-8) in this study. We found mean plasma PZ levels in haemodialysis patients and healthy controls 6.95+/-2.93 microg/ml and 3.06+/-0.81 microg/ml, respectively (p<0.005). Increased level of PZ which influences the action of thrombin on its protein substrates and inhibitors may contribute to the haemostatis alterations in ESRF patients, in addition to other well known abnormalities in the coagulation and fibrinolytic system.

Adult↗

Nasopharyngeal angiofibroma in a patient with haemophilia A: a bleeding tumour in a bleeding-prone patient.

Nasopharyngeal angiofibroma is a highly vascular tumour which occurs almost exclusively in adolescent males. Although it is histologically benign, it may cause serious clinical problems because of its tendency to bleed profusely during surgery. This paper presents the first case of nasopharyngeal angiofibroma in a patient with haemophilia A, another well-known disease of bleeding tendency. In this case the tumoural mass was surgically removed with effective factor VIII replacement without any bleeding complication.

Adolescent↗

Serum thrombopoietin levels in haemodialysis patients: involvement of arteriovenous fistula.

BACKGROUND: Thrombopoietin (Tpo) is a recently cloned growth factor which plays a critical role in the regulation of thrombopoiesis. Tpo has also been shown to stimulate in vitro and in vivo erythroid cell growth. Although Tpo transcripts were detected in hepatocytes, proximal tubules and endothelium, mechanisms regulating the level of circulating Tpo have not been fully delineated. Changes in the vessel wall and blood flow in arteriovenous fistula (AVF) might alter Tpo activity. METHODS: Serum thrombopoietin levels and serum erythropoietin levels in samples concurrently obtained from venous returns of AVF and contralateral peripheral veins in 31 haemodialysis patients were determined and compared with 12 healthy controls. Levels were also compared between 14 haemodialysis patients (group I) treated with recombinant human erythropoietin (rHu-Epo) and 17 haemodialysis patients (group II) not requiring rHu-Epo. RESULTS: Serum Tpo levels (44.8 +/- 23.9 pg/ml, vs 129.9 +/- 113.6 pg/ml, P<0.05) and platelet counts (194 +/- 55, 10(6)/ml vs 273 +/- 94. 10(6)/ml, P<0.05) of haemodialysis patients were lower than healthy controls. Serum Tpo levels were inversely correlated with platelet counts in the control group (R=-0.61, P<0.05), but not in haemodialysis patients. Tpo concentrations of AVF samples were lower than peripheral venous samples (31.6 +/- 17.7 pg/ml vs 44.8 +/- 23.9 pg/ml, P=0.001). No significant difference was present between the serum Tpo concentrations of haemodialysis patients in group I and group II. Serum Tpo levels were not correlated with haemoglobin levels or serum erythropoietin levels in haemodialysis patients. CONCLUSION: Decreased serum Tpo levels despite low platelet counts in haemodialysis patients suggest that the proposed feedback mechanism of platelet uptake of Tpo is not fully operative in these patients. Moreover, AVF might affect the local production and/or catabolism of this growth factor.

Adolescent↗

Thrombosis involving the major veins with heterozygote factor V Leiden mutation as the only risk factor.

A 27-year-old man was admitted to our hospital with the complaints of swelling of his face and lower limbs. Echocardiography showed minimal pericardial effusion accompanied by disordered diastolic function. Cardiac catheterization was performed to rule out constrictive pericarditis. Normal pressure tracings of the right heart rule out constrictive pericarditis, however, a narrowing of the inferior vena cava was observed. Venographies of the inferior and superior vena cavae showed extensive thrombotic involvement of these great veins. Protein C, protein S, anticardiolipin antibodies, fibrinogen, antithrombin-III, activated protein C resistance, and factor V levels were in normal limits. Heterozygosity for factor V Leiden mutation was detected. We conclude that factor V Leiden mutation can cause extensive thrombotic involvement of major veins and should be considered in idiopathic thrombosis of them.

Adult↗

Clinical significance of hemostatic markers and thrombomodulin in systemic lupus erythematosus: evidence for a prothrombotic state.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder with overwhelming thrombotic states. The precise pathogenetic mechanisms underlying the prethrombotic state in SLE is not fully understood, but interactions between the antiphospholipid antibodies and antigen targets on the coagulation components have been incriminated to play fundamental roles. To evaluate this issue, 34 women with antiphospholipid antibody negative SLE were investigated for molecular markers of blood coagulation and fibrinolytic activity: prothrombin fragment1+2 (PF1+2), thrombin-antithrombin complex (TAT), plasmin-alpha2-antiplasmin inhibitor complex (PAP), and tissue factor pathway inhibitor (TFPI). We also analysed plasma soluble thrombomodulin (sTM) levels. SLE disease activity was determined using the SLE Disease Activity Index (SLEDAI). Concentrations of TAT, PAP, PF1+2 and sTM were significantly elevated (P<0.0001, P=0.0002, P<0.0001, and P<0.0001, respectively), while TFPI antigen levels were found to be reduced (P<0.0001) in patients with SLE compared to the control group. In patients with active SLE, anti-ds DNA levels were correlated positively with plasma TAT (P<0.05), PF1+2 (P<0.05), and sTM (P<0.01) concentrations and negatively with plasma TFPI levels (P<0.05). SLEDAI scores were correlated positively with plasma TAT (P<0.01), PF1+2 (<0.01), and sTM (P<0.01) levels. This study illustrates that both a prethrombotic state and a compensatory fibrinolytic process secondary to subclinical intravascular coagulation might coexist in SLE with elevated sTM levels, indicating impaired endothelial functions.

Adult↗

Circulating thrombomodulin, thrombospondin, and fibronectin in acute myeloblastic leukemias.

In this study, soluble thrombomodulin (TM) was measured as an indicator of endothelial injury in acute myelocytic leukemia (AML) together with fibronectin (FN) and thrombospondin (TS). The study group comprised of 17 (6 men, 11 women; aged 34 +/- 10 years; range 21-61 years) newly diagnosed AML patients. There was infection in 6 patients. Twelve (4 men, 8 women; aged 31 +/- 11 years; range 18-55 years) healthy subjects were studied as the control group. Plasma soluble TM levels were significantly higher in AML patients than in the healthy control group (116.6 +/- 13.7 vs 37.2 +/- 1.75 ng/ml, respectively (mean +/- SEM), p < 0.01). Plasma FN levels were found to be significantly higher in AML patients compared to the control group (15.9 +/- 2.69 vs 8.1 +/- 2.46 ng/ml, respectively (mean +/- SEM). p < 0.01 ). Plasma FN levels in infected patients were significantly lower than in non-infected patients (6.47 +/- 1.3 vs 21.0 +/- 3.1 ng/ml, respectively (mean +/- SD), p < 0.01). Plasma TS levels in the patient group were significantly lower than in the control group (20.6 +/- 1.45 vs 120.8 +/- 18.2 ng/ml, respectively (mean +/- SEM), p < 0.01). In one patient with M7 megakaryoblastic leukemia who also had a high platelet count, plasma TS levels were significantly higher than that in other patients.

Adult↗

Perianal infections in patients with leukemia: importance of the course of neutrophil count.

PURPOSE: This study was performed to evaluate relations among neutrophil count (including its course), type of lesion, treatment, and prognosis in patients with leukemia and perianal infection. METHODS: Medical records of patients with acute and chronic leukemia who were followed during the last five years were reviewed retrospectively. RESULTS: The incidence of perianal infections was found to be 7.3 percent in 259 patients with acute leukemia. Only 1 of 108 patients with chronic leukemia suffered from this problem. Twenty percent of all patients with this complication died as a result of sepsis. Perianal abscess was the sole and obligatory indication for surgical treatment in our patients. There were ten patients in each treatment group. The operative group had better results (9 cures, 1 complication vs. 3 cures, 7 complications). However, median neutrophil count at diagnosis was notably higher in the operative group 1,280/mm3 vs. 96/mm3; P = 0.075). Also, significantly more frequent abscess formations and, consequently, operative treatments were performed in patients with a period of normal neutrophil counts during the infection compared with continuously neutropenic patients (9 operative, 4 nonoperative vs. 1 operative, 6 nonoperative; P = 0.057). Ten cures, three complications vs. two cures, five complications (3 mortalities) were present in patients with and without normal neutrophil counts, respectively (P = 0.062). When only severely neutropenic patients were considered, four patients in the surgery group had normal neutrophil counts before or shortly after surgery. However, only two of eight patients with perianal cellulitis had normal counts during full-course infection (P = 0.06). CONCLUSIONS: The course of the neutrophil count during infection was an important factor affecting the perianal lesion, and indirectly, choice of treatment and prognosis. A period of normal counts during infection usually led to well bordered and fluctuant lesions, and the prognosis was acceptable with operative treatment. However, continuously neutropenic patients developed nonfluctuating indurations. We found disappointing results with nonoperative treatment of such patients. In all studies, regarding treatment of perianal infections in neutropenic patients, the course of the neutrophil count and indications for surgery should be clarified to get reliable results.

Adolescent↗