Ekrem Muftuoglu

Prothrombin G20210A gene mutation with LightCycler polymerase chain reaction in venous thrombosis and healthy population in the southeast of Turkey

Venous thrombosis (VT) is a common disease, with an annual incidence in the general population of approximately 1 per 1000. The prevalence of genetic risk factors for thrombosis varies greatly in different parts of the world. Prothrombin G20210A (PT G20210A) gene mutation has been recently identified as a common risk factor in venous thrombosis. Sixty-one patients with VT, differing in age and sex, and 340 healthy subjects were consecutively enrolled into our study to determine the prevalence of PT G20210A in VT and in the healthy population of the southeast of Turkey. The mutation was identified with fluorescence resonance energy transfer (FRET) with the LightCycler polymerase chain reaction. The PT G20210A mutation was found to be 6.5% (4/61) in the VT group and 1.2% (4/340) in the healthy group (P = 0.021). Three patients with VT had a heterozygous PT G20210A mutation, and the other patient with VT had both Factor V Leiden and PT G20210A mutations. We showed that this method may be used safely for detection of the PT G20210A gene mutation, and the prevalence of PT G20210A mutation is significantly higher in patients with VT than in the healthy population in the southeast of Turkey.

Hepatitis C virus in patients with non-Hodgkin's lymphoma in southeastern Anatolia region of Turkey: A prospective case-control study of 119 patients

Hepatitis C virus (HCV) has been associated with several extrahepatic disorders including mixed cryoglobulinemia (MC), autoimmune thyroiditis, Sjogrens syndrome. Such associations have led to the suggestion that HCV may participate in the development of various immunmediated disorders. Recently, it has been hypothesised that HCV might act as a trigger for the development of monoclonal B-cell disorders such as non-Hodgkins lymphoma (NHL). Discordant data have been reported in different geographic regions of the world. The aim of this prospective case-control study was to detect the prevalence of HCV in patients with NHL in southeastern Anatolia region of Turkey. In this study, HCV antibody prevalence and cryoglobulinemia were investigated in 119 patients with histologically diagnosed NHL. The control group consisted of 117 patients who visited the outpatient clinic of internal medicine. None of the patients had HCV antibody positive (0%) with the enzyme immunoassay and reverse transcriptase polymerase chain reaction (RT-PCR). One of the control patients had positive HCV antibody (0.9%). Our data does not support the association between HCV infection and NHL in southeastern Anatolia region of Turkey.

Factor V Leiden mutation in venous thrombosis in southeast Turkey.

Venous thrombosis (VT) is a common disease, with an annual incidence in the general population of approximately 1 per 1,000. Factor V Leiden mutation (G1691A) (FVL) is the most common risk factor in venous thrombosis. The prevalence of FVL for thrombosis varies greatly in different regions of the world. FVL mutation has been identified both by conventional method and fluorescence resonance energy transfer (FRET) with the LightCycler. Sixty-one patients with VT, different in age and sex, were consecutively entered into this study to assess the prevalence of FVL in VT in southeast Turkey. FVL mutation was found in 24.6% (15/61). Fourteen individuals were heterozygous and 1 homozygous, a rate of 22.9% and 1.6%, respectively. In conclusion, the authors suggest that FVL mutation is common in patients with venous thrombosis in southeast Turkey.

A case of essential mixed cryoglobulinemia and associated acquired von-Willebrand disease treated with rituximab.

Current treatment options of essential mixed cryoglobulinemia (EMC); include immunosuppressive approaches, such as corticosteroids, cyclophosphamide, plasma exchange, other cytotoxic drugs in moderate to severe manifestations. Some controlled studies have been carried out to assess the efficacy of anti-CD20 monoclonal antibody, rituximab in patients with hepatitis C (HCV) related cryoglobulinemia (CG) and in patients with autoimmune disorders. Recent trials and some case reports demonstrate a beneficial role for rituximab in HCV related mixed CG. Although, the published evidence for treatment of EMC with rituximab is restricted to case reports, which have shown positive results. Several diseases include lymphoproliferative and myeloproliferative disorders, solid tumors, immunological disorders, cardiovascular disorders and some drugs associated with acquired von Willebrand disease (avWD). CG, which is a kind of immune complex disease, may be related with development of autoantibodies to various autoantigens. In this present case report, we showed the efficacy of rituximab in a 21-year-old female patient, suffered from neuropathy and arthralgia related with EMC, and developed avWD, presented with mucosal bleeding associated with CG. von Willebrand factor activity of our patient also increased with controlling the underlying disease, EMC by rituximab. This case demonstrate that rituximab may be an effective treatment option in EMC and avWD mainly related to CG.

Molecular basis of beta-thalassemia mutations in Diyarbakir in the southeastern region of Turkey.

b-Thalassemia (thal) is a common single gene disorder; it has been estimated that 3% of the world’s population (150 million people) carry a thalassemic gene. b-Thalassemia is an autosomal recessive disease characterized by a hypochromic, hemolytic anemia and dependence on blood transfusions to sustain life (1). Heterozygote carriers are essentially normal. They can usually be detected by screening red cell indices, that demonstrate a reduced mean corpuscular hemoglobin (Hb) value, and an elevated Hb A2 level (1). b-Thalassemia has a high frequency in the Mediterranean Basin, Africa, India, Southeast Asia, Iran, and Turkey. This disease is the most common genetic disorder in Turkey. Molecular cloning and DNA sequencing led to the identification of several mutations responsible for defect in the gene function (2). In the Turkish population, Professor Nazli Basak and her colleagues (Bogazici University, Istanbul, Turkey) have characterized more than 18 different mutations (3–5). The six most frequent alleles, accounting for about 70% of the cases, are IVS-1-110 (G!A), IVS-I-6 (T!C), the frameshift at codon (FSC) 8 ( AA), IVS-I-1 (G!A), 30 (T!A), and FSC 5 ( CT). We report here the results of a molecular screening carried out in a population from the southeastern region of Turkey, a region with an unknown incidence of thalassemia, by

Intracranial meningeal extramedullary hematopoiesis inducing serious headache in a patient with idiopathic myelofibrosis.

To the Editor: Extramedullary hematopoiesis (EMH) is a common finding in idiopathic myelofibrosis and is generally found in the liver, spleen, and lymph nodes. Involvement of other sites, such as the intrathoracic cavity, kidney, and thyroid, has been reported. However, meningeal EMH has rarely been reported in patients with idiopathic myelofibrosis. Some diseases may be causes of intracranial masses, and diagnosis is difficult. We present an 18-year-old patient with idiopathic myelofibrosis and an intracranial meningeal diffuse mass due to EMH admitted to our hematology clinic with refractory headache, dyspnea, fatigue, and anemia. He had been experiencing frequent headaches for the past 3 weeks. There was no history of trauma or primary malignancy. Six years prior to the admission he had been diagnosed with myelofibrosis. On physical examination, his blood pressure was 110/70 mm Hg, pulse 94 beats per minute, and respiratory rate 18 breaths per minute; the abdomen was distended and the liver enlarged. Splenectomy was done for thrombocytopenia and painful splenomegaly 2 months ago. Hemoglobin level was 9.2 g/dL, white blood cell count 4 , 5 0 0 / m m 3 , a n d p l a t e l e t c o u n t 65,000/mm, and a peripheral blood smear revealed anisocytosis, poikilocytosis, teardrop cells, and leukoerythroblastic changes. Bone marrow aspiration and biopsy revealed fibrosis and focal hypercellular marrow and megakaryocytic hyperplasia. Biochemical parameters, chest radiography, and echocardiographic examination were normal. MRI showed diffuse signal enhancement surrounding the brain. Bone marrow of whole body and cranium SPECT studies were obtained using 10 mCi Tc nanocolloid. Cross sections of transsagittal, transaxial, and coronal images of the brain were obtained during the SPECT study. Increased radiotracer involvement was observed in the left temporal and left occipital bone more clearly than in the frontal, parietal, and right temporal areas. In addition, increased radiotracer uptake was observed in the lateral sulcus bilaterally, especially in the cerebral longitudinal fissure. In planar images, the liver was enlarged and radiotracer uptake was increased. In addition, increased radiotracer involvement was observed in the femur and tibia. Bone scintigraphy with 20 mCi Tc MDP showed increasing osteoblastic activity in the left frontal and lateral parietal bones and in both shoulders, knee and ankle joints, and both metatarsal bones. Bilateral parietal and left frontal bone involvement was detected on both bone marrow and whole body scintigraphy. A biopsy of the mass revealed extramedullary hematopoiesis composed of erythroblasts, mature and immature myeloid cells, and megakaryocytes. We concluded that these represented foci of EMH. Headache was slightly decreased and MR images were sustained after 18 Gy (9 fr at 11 days) external cranial radiotherapy. A 5-month follow-up showed that the symptoms had not resolved completely. Patients with EMH may be divided into two main groups. The first group shows paraosseous foci that may result from herniation of medullary tissue from the underlying bone. This is seen in hemolytic disorders such as thalassemia and sickle cell anemia, where the marrow has tremendous activity. The second group shows extraosseous soft tissue foci, which may arise from multipotential stem cells. This occurs when the marrow activity is ineffective, as in idiopathic myelofibrosis or, rarely, with toxic or tumoral marrow destruction. Noninvasive imaging methods can be used to help establish the diagnosis of EMH. CT, MRI, and radionuclide imaging using Tc nanocolloid can confirm meningeal intracranial mass due to EMH. However, biopsy is needed to provide cytologic or histologic confirmation. The first description of the cranial imaging findings in EMH was published by Lund and Aldridge. Four patients with intracranial masses of hematopoietic tissue in the subdural space were reported. Landolfi et al reported the occurrence of meningeal masses causing exophthalmos and fever in a patient with myelofibrosis secondary to polycythemia vera. The patient subsequently developed a rapidly worsening tumor-like syndrome with hemiparesis, aphasia, and loss of sphincter control. Radiotherapy produced a complete and stable regression of clinical symptoms and a marked reduction of meningeal masses. Kandel et al reported a patient with polycythemia vera and meningeal masses of 9 years’ duration who developed increased intracranial pressure related to a mass obliterating the sagittal fissure. Although clinically and radiologically simulating a meningioma, biopsy revealed EMH involving the falx cerebri. This case illustrates that myeloproliferative disease can present with clinical symptoms and radiologic features similar to intracranial tumors. Intracranial EMH should be considered in the differential diagnosis of patients presenting with refractory headache, chronic anemia, and an extramedullary tumor-like appearance.

Hodgkin’s disease variant of richter’s transformation

Hodgkin’s disease rarely develops in patients with B-chronic lymphocytic leukemia. Patients developing Hodgkin’s disease after the diagnosis of chronic lymphocytic leukemia have been called the “Hodgkin’s disease variant of Richter’s transformation.” We present a 62-yr-old man with a 17-mo history of chronic lymphocytic leukemia, who clinically and hematologically on remission was admitted to our clinic because of rapidly developing right cervical lymphadenopathy. He was diagnosed with lymph node biopsy as a mixedcellularity Hodgkin’s disease.