Birol Guvenc

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

Introduction β-Thalassemia and hemoglobinopathies are common genetic disorders in Turkey and in this retrospective study our aim was to determine the frequency of β-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 β-globin gene was performed with β-Globin StripAssay. Results Of 3000 cases, 609 were diagnosed as β-thalassemia or hemoglobinopathy. We have found that the rates of occurrence of β-thalassemia and hemoglobinopathies are 13.46% and 6.83% respectively in this area. We have identified 18 different β-thalassemia mutations and three separate abnormal hemoglobins: HbS, HbD Los Angeles, and HbE. In molecular analyses, β-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, β-thalassemia and hemoglobinopathies still seem to be a public health problem in Adana.

Molecular Characterization of α-Thalassemia in Adana, Turkey: A Single Center Study

Background/Aim: α-Thalassemia (α-thal) is a widespread genetic disorder throughout the world caused primarily by reduced synthesis of the α-globin chains, and it has been found at a high incidence in Turkey. Our aim in this study was to determine the frequency and molecular properties of α-thal in Adana, Turkey. Material and Methods: A total of 3,000 individuals comprising premarital couples or patients with anemia were screened between 2007 and 2008. Hematological parameters were analyzed using an automatic cell counter, and to detect the carriers of hemoglobin variants, high-performance liquid chromatography was used. Molecular screening of the α-globin gene was carried out by an Alpha-Globin StripAssay® which is based on multiplex PCR for specific amplification. Results: We have identified 225 cases with α-thal and found that the prevalence of α-thal is 7.5% in this area. In molecular analyses, the α-thal gene mutations α3.7, α4.2, --MED, --20.5, αPA-2α, αααanti-3.7, and αPA-1α were detected. Conclusion: Our results showed that the α-thal mutations represent a great heterogeneity and that the -α3.7 deletion has the highest frequency in Adana.

Lymphoma of the breast in a male patient

Primary lymphoma of the breast is very rare especially in a male patient. Treatment alternatives include surgery, chemotherapy, immunotherapy and radiation. It is still controversial which combination is the best. Here, we report a male patient who presented with a left breast mass. The excisional biopsy was applied, and pathological assessment revealed marginal zone lymphoma. Both conventional computed tomography and 18)F-Fluorodeoxyglucose positron emission tomography/computed tomography were used for staging. The clinical stage was IIE for Ann Arbor staging and so local radiation following chemo immunotherapy was planned. Left-sided primary breast lymphoma in a male patient is a very rare entity. Treatment modalities are still controversial. Some authors believe that primary breast lymphomas have poor prognosis, and they must be treated aggressively with combined treatment modalities. Another important point is that 18)F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET)/CT could be used for staging of disease and assessing treatment response in a patient with primary breast marginal zone lymphoma.

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, andP < .01). Mean and end-diastolic velocities in the segmental arteries (P < .01, andP < .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 patients were significantly higher than the RI in group 1 patients and the control subjects, respectively. Total PI (P < .003;P < .0001) and total RI (P < .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.

Treatment of acute carbon-monoxide poisoning with therapeutic erythrocytapheresis: Clinical effects and results in 17 victims

Seventeen cases of acute carbon-monoxide poisoning were treated with therapeutic red cell-exchange. Glasgow Coma Scale score was used to evaluate the level of consciousness. The mean carboxyhemoglobin level decreased from 0.286 ± 0.1805 (28.6 ± 18.05%) to 0.0613 ± 0.0418 (6.13 ± 4.18%) and Glasgow Coma Scale score increased from 10 ± 3 to 13.76 ± 1.89. While 11 patients scored 15 at the end of the treatment, four scored 15 in an hour after the treatment. None of the patients died. Two victims (11.7%) experienced ischemic encephalopathy. Therapeutic red cell-exchange therapy can be an effective treatment in reducing mortality and morbidity in carbon-monoxide poisoning.

A Case Report of the Cascade Filtration System: A Safe and Effective Method for Low‐density Lipoprotein Apheresis During Pregnancy

Women with familial hypercholesterolemia (FH) should be treated effectively during pregnancy, as elevated low‐density lipoprotein cholesterol (LDL‐C) levels may result in life‐threatening consequences. Hydroxymethylglutaryl‐coenzyme A reductase inhibitors are contraindicated during pregnancy, therefore LDL apheresis should be considered in the management of such pregnant cases. There are five different methods of selective LDL apheresis: heparin‐induced extracorporeal LDL precipitation, double filtration plasmapheresis, direct adsorption of lipoproteins, dextran sulfate adsorption, and LDL immunoadsorption. The cascade filtration system is another modern and effective method for the extracorporeal elimination of LDL‐C, although it is not as selective as the methods mentioned above. Herein, we present the case of a pregnant woman with heterozygous FH and extremely elevated LDL‐C levels who has been successfully treated with the cascade filtration system until delivery. As far as we can ascertain, LDL apheresis with the cascade filtration system during pregnancy has not yet been reported in the literature.

Severe acetaminophen poisoning treated with a fractionated plasma separation and absorption system: A case report.

Acetaminophen is an analgesic drug that is frequently used in suicide attempts. In this paper, we report on a 17-year-old girl who was admitted to an emergency department 15 hours after taking acetaminophen pills in a suicide attempt. Her serum acetaminophen level was 73 mg/L on admission; she had elevated liver enzymes suggesting hepatic necrosis. She was started on N-acetyl cystein (NAC), and treated successfully with a fractionated plasma separation and absorption system.

Hepatitis B, Hepatitis C, Human immunodeficiency virus and syphilis frequency among blood donors: A single center study

We aimed to provide updated results for seroprevalence of hepatitis B, hepatitis C viruses while presenting first data for human immunodeficiency virus and syphilis seropositivity amongst blood donors in Adana, Turkey. Screening and confirmatory test results of 62,461 donors were evaluated. HBsAg, anti-HCV, anti-HIV1/2 and syphilis seropositivity was 1.92%, 0.48%, 0.20%, 0.18% respectively, based on screening tests, and 1.66%, 0.05%, 0.003%, 0.10% respectively, according to confirmatory tests. Transfusion-transmitted infections (TTI) was more prevalent in low-educated donors. HBsAg and syphilis seropositivity rates were higher in married subjects. We found that the prevalence of HBV and HCV was significantly decreased in the last two decades in Adana. Importantly, this study provides first data in HIV and syphilis seropositivity rates among blood donors in our region and both HIV and syphilis seroprevalences were found to be low compared to many regions of Turkey. However, considering the fact that increasing number of immigrants may change prevalences and trends of TTI both in Adana and in Turkey, strict monitorization and yearly reporting of TTI rates seem necessary to be able to take proactive measures.

Outcomes with frontline nilotinib treatment in Turkish patients with newly diagnosed Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase

ABSTRACT Objective: Nilotinib is a BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of patients with chronic myeloid leukemia in chronic phase (CML-CP). This study was the first prospective evaluation of the efficacy and safety of nilotinib in Turkish patients with newly diagnosed CML-CP. The primary endpoint of the study was the rate of major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [BCR-ABL1IS]) by 12 months. Methods: Patients with newly diagnosed CML-CP were treated with nilotinib 300 mg twice daily. This analysis was based on the first 12 months of follow-up in a 24-month study. Results and Conclusions: Of 112 patients enrolled, 66.1% (80% CI, 59.7–72.0%) achieved MMR and 22.3% achieved a deep molecular response of MR4.5 (BCR-ABL1IS ≤ 0.0032%) by 12 months. During the first year of treatment, 1 patient progressed to blast crisis and 2 patients died. Safety results were consistent with previous studies. Most adverse events (AEs) were grade 1/2. Most frequently reported nonhematologic AEs of any grade were elevations in bilirubin, alanine aminotransferase, and triglycerides. These results support the use of nilotinib 300 mg twice daily as a standard-of-care treatment option for patients with newly diagnosed CML-CP.

β-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 β-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 β-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 β-globin genes. The –α3.7/αα deletion was the commonest defect in the α-chain as expected, followed by α3.7/–α3.7 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 αPolyA-2α/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 β-globin chain (–α3.7/αα with IVSI.110/S), and also a case who had –α3.7/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 β-thalassemia trait during the screening programs for premarital couples, especially in populations with a high frequency of hemoglobinopathies.