ß-Globin chain abnormalities with coexisting α-thalassemia mutations.

INTRODUCTION: The frequency of hemoglobinopathies is still high in Adana, the biggest city of the Cukurova Region that is located in the southern part of Turkey. Our aim was to identify the concomitant mutations in α- and ß-globin genes which lead to complex hemoglobinopathies and to establish an appropriate plan of action for each subject, particularly when prenatal diagnosis is necessary. MATERIAL AND METHODS: We studied the association between the ß-globin gene and α-thalassemia genotypes. The reverse hybridization technique was employed to perform molecular analysis, and the results were confirmed by amplification refractory mutation system (ARMS) or restriction fragment length polymorphism (RFLP) technique. RESULTS: We evaluated 36 adult subjects (28 female and 8 male; age range: 18-52 years) with concomitant mutations in their α- and ß-globin genes. The -α(3.7)/αα deletion was the commonest defect in the α-chain as expected, followed by α(3.7)/-α(3.7) deletion. Twenty-five of 36 cases were sickle cell trait with coexisting α-thalassemia, while seven Hb S/S patients had concurrent mutations in their α-genes. The coexistence of α(PolyA-2)α/αα with Hb A/D and with Hb S/D, which is very uncommon, was also detected. There was a subject with compound heterozygosity for ß-globin chain (-α(3.7)/αα with IVSI.110/S), and also a case who had -α(3.7)/αα deletion with IVSI.110/A. CONCLUSIONS: Although limited, our data suggest that it would be valuable to study coexisting α-globin mutations in subjects with sickle cell disease or ß-thalassemia trait during the screening programs for premarital couples, especially in populations with a high frequency of hemoglobinopathies.

ß-Thalassemia mutations and hemoglobinopathies in Adana, Turkey: results from a single center study.

INTRODUCTION: ß-Thalassemia and hemoglobinopathies are common genetic disorders in Turkey and in this retrospective study our aim was to determine the frequency of ß-thalassemia and hemoglobinopathies in Adana, which is one of the biggest cities located in the southern part of Turkey. MATERIAL AND METHODS: Data from 3000 individuals admitted to Seyhan Hereditary Blood Disorders Center in Adana were evaluated. The blood samples were collected into EDTA-containing tubes and hematological parameters were analyzed using an automatic cell counter. High performance liquid chromatography technique was used to determine the type of hemoglobin. Molecular screening of the ß-globin gene was performed with ß-Globin StripAssay. RESULTS: Of 3000 cases, 609 were diagnosed as ß-thalassemia or hemoglobinopathy. We have found that the rates of occurrence of ß-thalassemia and hemoglobinopathies are 13.46% and 6.83% respectively in this area. We have identified 18 different ß-thalassemia mutations and three separate abnormal hemoglobins: HbS, HbD Los Angeles, and HbE. In molecular analyses, ß-thalassemia gene mutations of IVSI.110 (G > A), codon 8 (-AA), IVSI.1 (G > A), IVSI.6 (T > C), -30 (T > A), IVSII.1 (G > A), codon 39 (C > T), codon 44 (-C), IVSI.5 (G > C), codon 5 (-CT), codon 8/9 (+G), IVSII.745 (C > G), codon 22 (7bp del), -101(C > T), codon 36/37 (-T), IVSI.15 (T > G), codon 6 (-A), -88 (G > A) were detected. CONCLUSIONS: Considering the high incidence of mutations that we have found, ß-thalassemia and hemoglobinopathies still seem to be a public health problem in Adana.

Nonsense ß-thalassemia mutation at codon 37 (TGG>TGA), detected for the first time in three Turkish cases.

Thalassemias are genetically heterogeneous group of disorders with reduced or absent production of globin. ß-Thalassemia major can be caused by homozygosity or compound heterozygosity for ß-globin gene mutation. Here we report, for the first time in Turkey, three cases who carry the nonsense ß-thalassemia (ß-thal) mutation at codon 37 (TGG>TGA; Trp→Stop) causing premature stop codon.

Tissue doppler imaging and NT-proBNP levels show the early impairment of ventricular function in patients with beta-thalassaemia major.

Beta-thalassaemia major is a chronic haemolytic anaemia, and congestive heart failure (CHF) is the most common cause of death in this disease. N terminal pro B type natriuretic peptide (NT-proBNP) increases with the severity of CHF and predicts the prognosis. The aim of this study was to investigate the relation between left ventricular systolic and diastolic function determined by standard pulsed wave Doppler (PWD), tissue Doppler imaging (TDI) and NT-proBNP in patients with beta-thalassaemia major. Thirty-four patients with beta-thalassaemia major and 34 healthy individuals were included in the study. Blood samples were taken for NT-proBNP. All patients and controls underwent echocardiographic examination. All cardiac chambers were significantly increased in the patient group. Left and right ventricular (LV, RV) ejection fractions and all diastolic parameters were normal in the patients and controls. Tissue Doppler imaging (TDI) showed a significant decrease in LV and RV Sm velocities in patients compared to the controls. NT-proBNP levels were also significantly higher in the patient group. There was a negative correlation between serum NT-proBNP levels and LV Sm and RV Sm velocities in patients (r = -0.426, P = 0.006 and r = -0.409, P = 0.009, respectively). Linear regression analysis showed that LV Sm and RV Sm were independent predictors for NT-proBNP. Our findings suggest that although iron overload in patients with beta-thalassaemia major impairs the systolic and diastolic functions of both ventricles, it impairs the systolic function earlier than diastolic function. Tissue Doppler imaging is an easy and reliable method in the early determination of ventricular dysfunction in these patients.

Clinical significance of hepatocyte growth factor, platelet-derived growth factor-AB, and transforming growth factor-alpha in bone marrow and peripheral blood of patients with multiple myeloma.

Angiogenesis is a process that plays an important role in the growth and progression of cancer; growing evidence suggests that neovascularization is important in hematologic malignancies. Increased angiogenic potential has been identified in multiple myeloma (MM). In this study, investigators simultaneously measured the levels of hepatocyte growth factor (HGF), platelet-derived growth factor-AB (PDGFAB), and transforming growth factor-alpha (TGF-alpha) through enzyme-linked immunosorbent assay in the bone marrow (BM) and peripheral blood (PB) of 30 patients with MM and 10 healthy controls. Differences in HGF values in BM sera were significant (P=.001) between patients and controls. In detailed analyses of HGF, PDGF-AB, and TGF-alpha, according to disease stage, a significant correlation was found between disease stage and BM HGF (P=.047), BM TGF-alpha (P=.021), and PB PDGF-AB (P=.006), respectively. When correlations between all other parameters were analyzed, significance was noted between PB TGF-alpha and lactate dehydrogenase (P=.02), PB TGF-alpha and PB HGF (P=.002), BM TGF-alpha and CD38 (P=.046), BM TGF-alpha and BM HGF (P=.000), BM TGF-alpha and BM PDGF-AB (P=.048), BM HGF and PB HGF (P=.044), and BM PDGF-AB and PB PDGF-AB (P=.000). BM HGF levels had a significant effect on overall survival, with disease severity assessed in terms of disease stage (P=.0018, log-rank test). These data show that in patients with MM, high levels of BM HGF, BM TGF-alpha, and PB PDGF-AB were associated with advanced disease stage; in addition, HGF played a significant role in disease processing and was related to disease severity. These findings have also led to the concept of a symbiotic relationship between the growth of myeloma cells and HGF, TGF-alpha, and PDGFAB in BM.

Renal vascular resistance in sickle cell painful crisis.

Vaso-occlusive painful crisis is one of the characteristic manifestations of sickle cell disease (SCD). We aimed to investigate the state of renal vascular resistance by means of Doppler ultrasonography during vaso-occlusive painful crisis in patients with SCD. The 60 patients with homozygous SCD who entered the study were divided into 2 groups. Group 1 included 45 patients who were living in steady-state conditions and had no history of transfusions within the 3 months before the initiation of the study. Group 2 consisted of 15 patients with signs of painful vaso-occlusive crisis during evaluation. Group 2 patients had significant reductions in 3 measures of flow velocity in both main renal arteries, compared with group 1 patients (P < .04, P < .001, and P < .01). Mean and end-diastolic velocities in the segmental arteries (P < .01, and P < .001, respectively) and end-diastolic velocities in the interlobar arteries (P < .04) were lower in group 2 patients than in group 1 patients. Analysis of resistive (RI) and pulsatile (PI) indices in the investigated arteries demonstrated that the RI of the renal (P < .001; P < .0001), segmental (P < .002; P < .0001) and interlobar (P < .001; P < .0001) arteries of both kidneys in group 2 < .0001; P < .0001) for both kidneys were markedly higher in group 2 patients than in group 1 patients and the healthy subjects, respectively. Our preliminary results suggest a reduction of renal blood flow and an increase in renal vascular resistance during painful crisis compared with steady-state SCD.

Sickle cell anemia patient with sarcoidosis-associated inguinal lymph node and lung infiltration.

Sarcoidosis is a chronic, systemic inflammatory disease of unknown etiology, characterized by noncaseating granulomatous infiltration of any organ. Sickle cell anemia (SCA) is the homozygoid form of sickle cell disease (SCD), which includes a group of genetic disorders characterized by production of an abnormal hemoglobin S (HbS). There are a few case reports with coexistence of sarcoidosis and SCA. We reported a 47-year-old female with SCA and sarcoidosis.

Plasmapheresis in the treatment of hyperthyroidism associated with agranulocytosis: A case report.

Plasmapheresis, also known as therapeutic plasma exchange, is used in the treatment of several disorders. Temporary improvement after plasmapheresis in cases with thyrotoxicosis has been reported. A 55-year-old woman presented with agranulocytosis induced by propylthiouracil and clinical signs of heart failure. Three sessions of plasmapheresis were performed. We observed an improvement of thyroid hormone levels and clinical findings as well. Plasmapheresis can be an option when drug treatment of thyrotoxicosis fails.

Systemic lupus erythematosus and thrombotic thrombocytopenic purpura: a case report.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterised by platelet aggregation causing microvascular occlusion. Early diagnosis and utilization of plasmapheresis can provide an improvement in prognosis. CASE REPORT: A 17 year old male with classical findings of TTP was later diagnosed as systemic lupus erythematosus (SLE). Plasmapheresis resulted in the significant amelioration of the course. CONCLUSION: The coexistence of TTP and SLE may facilitate a better understanding of in the pathophysiology of TTP. These association may provide the role of autoimmunity in TTP. SLE should be considered in the differential diagnosis of patients with TTP because of therapeutic implications.

Anti-D and Intravenous Immunoglobulin Treatments in Chronic Idiopathic Thrombocytopenic Purpura.

The aim of this prospective study was to evaluate the data from 29 patients diagnosed as chronic refractory idiopathic thrombocytopenic purpura (ITP) treated with anti-D immunoglobulin and intravenous immunoglobulin G (IVIG). We used anti-D and IVIG in 11 and 18 patients respectively in whom the previous treatments including corticosteroids and splenectomy had been unsuccessful. The complete response rates were significantly higher in IVIG arm (55.5% to 18.1%) with a duration of 8 weeks. The overall efficacy of IVIG in the chronic ITP is similar to previous data, however we found lower platelet responses in patients treated with anti-D that can be attributed to the lower sucess in the splenectomized patients.

Budd-Chiari syndrome associated with visceral leishmaniasis and factor V Leiden mutation.

We here report a case of subacute Budd-Chiari syndrome (BCS) related to Factor V Leiden (FVL) mutation in the presence of visceral leishmaniasis. A 17-year-old man was admitted to hospital because of abdominal pain, pretibial edema and fever. The clinical picture of BCS had been developed within several months. BCS was diagnosed by radiographic examination. On DNA analysis, a heterozygote Arg506Gln mutation in the factor V gene was found. Histological examination of the bone marrow showed intracellular leishmania amastigotes. Despite appropriate treatment patient's clinical condition deteriorated rapidly and died with multiorgan failure. FVL mutation is the most common procoagulant disorder and account for many cases of BCS. This case report demonstrates that in addition to duration and severity of the disease accompanying conditions including infections are prognostically significant for the outcome of this potentially lethal disease.

Immune thrombocytopenic purpura associated with Brucella and Toxoplasma infections.

Bacterial and protozoal infections can cause thrombocytopenia and may mimic idiopathic thrombocytopenic purpura (ITP). Brucella species and Toxoplasma are among the infectious agents with protean clinical manifestations which may induce immune thrombocytopenia. In rare cases, thrombocytopenia can be severe and may result bleeding into the skin and from mucosal sites. Prompt recognition of this complication and aggressive therapy are essential, since the mortality associated with bleeding into the central nervous system is high. We report two patients with complaints of severe epistaxis and thrombocytopenia associated with brucellosis and toxoplasmosis. Thrombocytopenic purpura in these cases responded well to the high-dose corticosteroid treatment with platelet recovery within 2-3 days. For cases with infection-induced immune thrombocytopenic purpura, short-term high-dose corticosteroids may be applied as an urgent therapy without worsening of the clinical condition.