Successful treatment of myelodysplastic syndrome-induced pyoderma gangrenosum.

We report successful treatment of a refractory myelodysplastic syndrome-associated pyoderma gangrenosum with the combination of thalidomide and interferon-alpha2a in a single patient. A non-healing wound developed on a 40-year-old woman's left thumb after minor trauma. Massive ulcerovegetative lesions developed after reconstruction surgery. Histopathological examination of the bone marrow and cytogenetic studies revealed an atypical myeloproliferative/myelodysplastic syndrome. The skin lesions resolved dramatically after two months of thalidomide and interferon-alpha2a combination therapy and the haematological status improved.

Predicting chronic leukaemias from assessment of complete peripheral blood counts.

The chronic leukaemias include two distinct chronic neoplastic disease states, namely chronic myelogenous leukaemia (CML) and chronic lymphocytic leukaemia (CLL). The aim of this study was to assess the utility of leucocyte count, neutrophil percentage and absolute lymphocyte count from differential complete blood count analyses as indicators of the possible presence of CML and CLL. Blood counts from 102 patients with histopathologically confirmed CML and CLL were compared with counts for 858 cancer-free control subjects. Optimal cut-off values were identified by selecting values with the highest sensitivity-specificity combination for each blood count parameter for the two diseases. The results indicated that any individual with mature-appearing lymphocytes at a level > 6.65 x 10(9)/l in the peripheral blood should be examined further for CLL, and that any individual with a leucocyte count > 18.0 x 10(9)/l or a neutrophil proportion > 72.6% should be investigated for CML.

Overt gastrointestinal bleeding in haematologic neoplasms.

BACKGROUND AND AIM: Patients with acute leukaemia suffer from various haemorrhages, most frequently due to thrombocytopenia. We could not reach any information regarding the frequency of gastrointestinal bleeding in acute leukaemia and decided to search this complication in patients with acute and chronic leukaemias and myeloproliferative disorders, retrospectively. PATIENTS AND METHODS: During a 6-year period, 291 patients with acute leukaemia, 52 patients with chronic leukaemia and 108 patients with myeloproliferative disorders had been followed. Thirty-two cases of overt gastrointestinal haemorrhage episodes (25 upper, 7 lower) were observed during the mentioned period. RESULTS: The frequency of bleeding episodes was 7.1% (32/451) in haematologic malignancies as a whole, 5.8% (17/291) for acute leukaemia, 1.9% (1/52) for chronic leukaemia and 13% (14/108) for myeloproliferative disorders. If the patients with myeloproliferative disorders in blastic phase were analysed separately, the ratio was 30% (6/20). Oesophagogastroduodenoscopy, which could be performed in 8 of 25 upper gastrointestinal haemorrhage episodes, revealed erosive gastritis in five patients and duodenal ulcers in three patients. Neutropenic enterocolitis was the underlying cause in all of the seven patients with lower gastrointestinal haemorhage. Five out of the seven patients had acute leukaemia. In 7 bleeding attacks, out of 32, the ultimate result was death. Generally, the haemorrhage was only a contributing cause of mortality. All of the mortality cases were patients with acute leukaemia. CONCLUSION: Especially, the patients with myeloproliferative disorders are prone to develop gastrointestinal haemorrhage. The manifestation is generally as upper gastrointestinal bleeding due to gastric erosions and duodenal ulcers. Lower gastrointestinal bleeding is frequently a problem of the patients with acute leukaemia. It is commonly a sign of neutropenic enterocolitis.

Non-Hodgkin's lymphoma complicating pregnancy: a case report.

A 40-year-old, gravida 3, para 2 woman was initially referred to our department at 31 weeks' gestation complaining of fever, night sweats, malaise in association with jaundice and pancytopenia. Cesarean section with excisional iliac lymph node biopsy was carried out following a period of expectant management. An 1,840 g healthy male infant with an Apgar score of 9 at 34 weeks of gestation was delivered. Histologic examination of the excised lymph node revealed non-Hodgkin's lymphoma (Histiocyte and T cell predominant B cell lymphoma). The patient was evaluated to have Stage II B disease. A chemotherapy regimen of CHOP/Rituximab was instituted with successful maternal-fetal prognosis.

Enhanced expression of the local haematopoietic bone marrow renin-angiotensin system in polycythemia rubra vera.

Local bone marrow (BM) renin-angiotensin system (RAS) affects physiological and pathological haematopoiesis, including erythropoiesis. In this study, quantitative expression of the messenger RNAs of the major RAS components--angiotensin-converting enzyme (CD143), renin and angiotensinogen--were measured in BM samples by quantitative real-time polymerase chain reaction, to evaluate the activity of local BM RAS in polycythemia rubra vera (PV) in comparison with normal erythropoiesis. The presence of CD143 was also investigated in the same BM samples by flow cytometry. Increased local synthesis of the major RAS components has been identified by demonstrating corresponding mRNAs in the BM of the patients with PV. Our findings indicate up-regulation of local BM RAS, together with down-regulation of the cell surface angiotensin-converting enzyme receptors, in the autonomous neoplastic clonal erythropoiesis of PV.

Neutropenic enterocolitis in adult leukemias.

Neutropenic enterocolitis is a frequent autopsy finding in adult patients with acute leukemias. The predisposing factors other than neutropenia are not clear. There are also contradictions about treatment. Therefore, this entity still presents a diagnostic and therapeutic dilemma for clinicians. This retrospective study was performed to determine the incidence of neutropenic enterocolitis in adult leukemic patients, to examine the possible risk factors, clinical characteristics and treatment outcome. The pathogenesis is also discussed considering clinical and laboratory findings of the patients. The incidence of neutropenic enterocolitis was 6.5% for acute myeloid leukemia and 4.6% for acute lymphoblastic leukemia. The mean absolute neutrophil count at diagnosis was 48/mm3 (median: 0/mm3). The median duration of severe neutropenia (absolute neutrophil count < or = 500/mm3) on follow-up before the diagnosis was 32 days. Thirteen out of 20 patients had received antineoplastic drugs within the last 12 days, but 2 had not. Fourteen patients had signs of peritoneal irritation and 3 of them underwent surgery. The others received supportive measures, i.e. bowel rest, intravenous fluids, combinations of wide spectrum antibiotics, transfusions, hemodynamic supports and nasogastric decompression, if necessary. All 3 patients who underwent surgery survived, whereas only 1 of the 11 who received other treatments did. Six patients without signs of peritonitis were treated with antibiotics and the mentioned supportive measures. Four survived, but the others died due to sepsis. In conclusion, considering some recent reports that stated good outcome with conservative measures in the presence or absence of peritonitis, there is still debate regarding the optimal choice of treatment. The importance of early diagnosis cannot be overemphasized. Signs of peritoneal irritation indicate a life threatening condition. Surgery can be performed successfully in such patients. Long duration of neutropenia may be an important risk for neutropenic enterocolitis.

Increased systemic coagulation activity in patients with rheumatic mitral stenosis: assessment of the clinical and echocardiographic determinants.

In this study, we aimed to determine systemic coagulation activity in patients with rheumatic mitral stenosis and to define determinants of a possible prethrombotic state. Peripheral venous plasma level of thrombin-antithrombin III complex was measured in 84 consecutive patients with rheumatic mitral stenosis who had no left atrial thrombus by transesophageal echocardiography. The patients had significantly higher thrombin-antithrombin III complex values (mean +/- SD = 9.6+/-15.9 ng/ ml) compared with the healthy subjects (2.1+/-1.8 ng/ml) (P<0.001). Among many clinical and echocardiographic variables, severe mitral regurgitation (odds ratio = 6.7, P<0.001) and left atrial spontaneous echo contrast (odds ratio = 22.8, P<0.001) appeared as significant predictors of the increased systemic coagulation activity in multivariate logistic regression analysis. In conclusion, systemic coagulation activity is increased in the patients with rheumatic mitral stenosis, and coexistence of severe mitral regurgitation and presence of left atrial spontaneous echo contrast are determinants of this increment.

Rational use of the PFA-100 device for screening of platelet function disorders and von Willebrand disease.

Two hundred and five patients referred for evaluation of platelet functions and 126 healthy controls were tested with the PFA-100 instrument. A cut-off value of 150 s for collagen/epinephrine (CEPI) closure time (CT) produced most acceptable sensitivity (90%), specificity (85.2%), and positive (82.6%) and negative (91.6%) predictivity values for screening of platelet function disorders and von Willebrand disease (vWD). All patients with vWD and Glanzmann thrombasthenia could be detected by PFA-100. Both CEPI and collagen/adenosine diphosphate (CADP) CTs were elevated in all of these cases. Sensitivity of the device was 81.6% for patients with platelet secretion defects. CADP CT was normal in 63.9% of the patients in this subgroup. Specificity (47%) and positive predictivity (57%) of the instrument were diminished in patients with low hemoglobin concentrations. Depending on the results, an algorithm was developed for screening of platelet function disorders and vWD with PFA-100.

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).

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 underlying 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.

Plasma thrombospondin in immune thrombocytopenic purpura.

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.

Protein C inhibitor and serum amyloid A in immune thrombocytopaenic purpura.

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.

[Anticardiolipin antibodies in autoimmune rheumatic diseases]. / Romatizmal otoimmün hastaliklarda antikardiyolipin antikorlarinin arastirilmasi.

In this study, ELISA and VDRL tests have been employed in order to detect ACL antibodies in sera samples obtained from 105 patients with SLE, RA, scleroderma, dermatomyositis, primary Sjögren's syndrome, vasculitis and pulmonary thromboemboli; Using by IFAT, AMA-type 5 and other autoantibodies, RIA anti-DNA antibodies were also tested in SLE patients. In sera obtained from the patients with RA; autoantibodies and RF have been investigated. In SLE cases, ACL antibodies were found to be positive in 55.5% of the patients. In RA cases the rate of ACL antibodies were found to be 51.7%. In SLE cases, the presence of IgG-ACL antibody was found to be in association with thrombosis and fetal loss; while IgM-ACL antibody was found to be in association with fetal loss only. Serologic parameters such as VDRL and AMA type 5 were significantly connected with the presence of ACL-IgG and IgM antibodies (p less than 0.05). In cases of RA connection was detected only between IgG-ACL antibody and thrombosis. Concerning the other rheumatic autoimmune diseases; ACL antibodies were detected in cases: 4 patients out of 11 scleroderma, 1 patient out of 7 vasculitis, 2 patients out of 5 primary Sjögren's syndrome, and 3 patients out of 6 pulmonary thromboemboli.

Increased erythrocyte aggregation as an indicator for an aggressive clinical course in Behçet's disease: a prospective study.

OBJECTIVE: Changes in blood rheology, especially increased erythrocyte aggregation (EA) might play an important part in the development of arterial and venous thrombotic lesions. A prospective study was designed to evaluate EA in patients with Behçet's disease (BD) and to see if this parameter is predictive for the future development of vascular complications, such as deep vein thrombosis of various organ systems and uveitis. METHODS: EA was measured by a photometric Myrenne aggregometer in 38 patients with BD at the time of initial diagnosis and in 40 age and sex matched healthy controls (HC). RESULTS: During a median follow up period of 13.5 months, 13 patients developed vascular-ocular complications (eight deep vein thrombosis, nine uveitis, and four both deep vein thrombosis and uveitis). Patients were further divided into two groups: BD-a with mucocutaneous symptoms and arthritis only; BD-b with associated vascular-ocular complications. EA values at high shear rate (M) and at low shear rate (M1) were compared among the groups. CONCLUSION: EA values at M and M1 were significantly higher in BD-b than BD-a and HC (p < 0.001). These results suggest that determination of EA rates might be useful to identify subgroups who are likely candidates for developing vascular-ocular complications in BD and management of factors known to affect blood rheology might be beneficial.

Selectins and IL-6 during the clinical course of idiopathic thrombocytopenic purpura.

'Stress thrombocytes', i.e. large and presumably hyperfunctioning platelets, is a well-known characteristic of patients with idiopathic thrombocytopenic purpura (ITP). Therefore, despite what may be severe thrombocytopenia these patients generally do not suffer from severe life-threatening hemorrhage. The plasma level of soluble P-selectin (sP-selectin) is a valuable marker reflecting platelet activation. Available data suggest that interleukin-6 (IL-6) may contribute to the regulation of megakaryocytopoiesis and platelet activity. The purpose of this study is to investigate the status and kinetics of IL-6 and selectins, which are involved in the platelet function, production, and immunologic functions, during the clinical course of ITP, that may be helpful for understanding the biology of the disease. Twenty-two ITP patients were studied prospectively in the course of their disease. Sixteen, 8 and 6 patients were available after platelet recovery, relapse and splenectomy, respectively. Fifteen healthy persons served as a control group. Higher levels of both sP-selectin and IL-6 were observed in all clinical stages of disease compared to the control group. However, more prominent elevations were present during active stages of ITP, i.e. pretreatment (p < 0.001 vs. control group for both sP-selectin and IL-6) and relapse periods (p < 0.001 vs. control group for both sP-selectin and IL-6). Pretreatment soluble L-selectin and soluble E-selectin levels were not different from the controls. Both sP-selectin (r = -0.32, p = 0.019) and IL-6 (r = -0. 41, p = 0.002) levels inversely correlated with platelet count during disease course. There was a positive correlation between the sL-selectin level and leukocyte count (r = 0.60, p < 0.001). These results suggest that residual platelets are activated in ITP, which offers a relatively benign clinical course compared to other thrombocytopenias. High IL-6 concentration during thrombocytopenia may be involved in compensatory megakaryocytopoiesis and augmented 'residual platelet' functions in ITP.

Pancytopenia with hypocellular bone marrow due to miliary tuberculosis: an unusual presentation.

In a patient who presented with fever, weight loss and abdominal swelling, blood counts revealed pancytopenia. Broad-spectrum empirical antibiotic treatment was started because of neutropenic fever, but without effect. The bone marrow was hypocellular with an increase in fat droplets. Peritoneoscopy was performed to evaluate ascites; in the liver biopsy specimen caseous granulomas were seen and the patient was found to suffer from miliary tuberculosis. Antituberculous therapy was begun and the patient recovered completely and the haematological parameters returned to normal.

Cytokines in Behçet's disease.

OBJECTIVE: Cytokines take place in immunologic and inflammatory reactions. The aim of this study was to describe the roles of various cytokines in the pathogenesis of Behçet's disease (BD). METHODS: Serum levels of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), soluble IL-2 receptor (sIL-2R), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were studied in 24 patients with active BD and 15 healthy adults as controls, by ELISA technique. Patients were separated into 2 groups according to the number of active organ systems (Group I: < 3 vs Group II: > or = 3). RESULTS: sIL-2R and age adjusted TNF-alpha levels were higher in patients with BD compared to controls (p = 0.004 and p = 0.002, respectively). But the median concentrations of Group I and Group II were not different. Serum levels of IL-1 beta, IL-2 and IL-6 were similar to the control group. CONCLUSION: High serum levels of sIL-2R and TNF-alpha indicate activation of the immune system in BD. But this finding may not be useful as a marker of disease activity.