Hemoglobin H Disease in Turkey: Experience from Eight Centers.

The purpose of this study was to research the problem of hemoglobin H (HbH) disease, to reveal the distribution patterns among different health centers, and to emphasize the importance of this disease for Turkey. A total of 273 patients were included from 8 hemoglobinopathy centers. The Antakya Hemoglobinopathy Center reported 232 patients and the remaining 7 centers reported 41 patients. PubMed was also searched for published articles related to Turkish patients with HbH disease, and we found 16 articles involving a total of 198 HbH patients. Most of the patients were reported from Antakya; thus, special attention should be paid to this region. This is a preliminary study to investigate the extent of the problem of HbH disease and it emphasizes the need for hematology associations or the Ministry of Health to record all cases of HbH disease in Turkey.

Thyroid Doppler indices in patients with sickle cell disease.

OBJECTIVE: To evaluate the intrathyroidal hemodynamic changes and thyroidal volume in sickle cell disease (SCD) patients. METHODS: Thirty-two patients with homozygous SCD and 32 control subjects were examined with color Doppler ultrasonography. None of the patients and control subjects had clinical or laboratory evidence of thyroid disease. RESULTS: SCD patients had significantly higher resistance index (RI) and pulsatility index (PI) values and lower thyroid volume compared with control group. CONCLUSION: Increased intrathyroidal RI and PI and decreased thyroid volume may be due to impaired thyroidal microcirculation. Further and follow-up studies are needed to explain the relationship between Doppler parameters and thyroid functions.

Quantitative brain diffusion-tensor MRI findings in patients with sickle cell disease.

OBJECTIVE: The aim of this study was to evaluate the microstructure of various regions of the brain using diffusion-tensor imaging (DTI) in patients with sickle cell disease (SCD) and in age- and sex-matched healthy control subjects. We also investigated the fiber tractography findings of the corpus callosum (CC) and corticospinal tracts (CSTs). SUBJECTS AND METHODS: Sixteen right-handed patients with SCD and 14 age- and sex-matched right-handed healthy control subjects were scanned using conventional MR sequences and DTI. Fractional anisotropy (FA) and apparent diffusion coefficients (ADCs) were calculated and regions of interest were selected in various brain areas (superior and inferior frontal, parietal, occipital, and temporal white matter areas), anterior and posterior periventricular areas, centrum semiovale, basal ganglia (lentiform nucleus, head of caudate nucleus), thalamus, cerebral peduncles, pons, cerebellar white matter areas, and CC. Diffusion-tensor tractography of the CC and CSTs was also performed. RESULTS: For the patients with SCD, significantly reduced FA values, increased ADC values, or both were seen clustered in several brain areas, including the CC, frontal white matter, centrum semiovale, periventricular areas, head of the caudate nucleus, thalamus, brainstem, and pons (p < 0.05). Statistically significant reductions in fiber counts in the first and fifth segments of the CC and in CSTs bilaterally were also observed in patients with SCD (p < 0.05). CONCLUSION: DTI shows microstructural abnormalities of various brain areas in patients with SCD.

Prevalence of abdominal ultrasonographic abnormalities in patients with sickle cell disease.

PURPOSE: The aim of this study was to evaluate the type and prevalence of abdominal ultrasonographic abnormalities in patients with sickle cell disease. MATERIALS AND METHODS: A total of 102 patients with sickle cell disease at the Center of Hemoglobinopathy of the Antakya State Hospital were screened for intra-abdominal abnormalities by abdominal ultrasonography (US). Eightyfour patients were homozygous for sickle-cell disease (S/S), and 18 patients were compound heterozygotes for sickle cell-Beta thalassemia (S/Beta(thal)). At the time of examination, 15.7% (16/102) of patients had undergone splenectomy, and 18.6% (19/102) of patients had undergone cholecystectomy. RESULTS: The most frequent US findings (expressed as percentages of all patients) were hepatomegaly (71.6%), renal enlargement (30.4%), autosplenectomy (33.3%), cholelithiasis (30.4%) and splenomegaly (17.4%). A bright liver was identified in 6 patients (5.9%), an echogenic pancreas in 4 patients (3.9%), and pancreatic punctate echogenic foci were identified in 5 patients (4.9%). Medullary or diffusely increased renal echogenicity was observed in 16 patients (15.7%). Sonographic findings typical of renal papillary necrosis were observed in one patient with S/S. Periportal lymphadenopathy was detected in 10 (11.9%) of 84 patients of the S/S group, and 2 (11.1%) of 18 patients of S/Beta(thal) group. CONCLUSION: Abdominal ultrasonographic imaging of patients with sickle cell disease revealed a high prevalence of abdominal abnormalities, especially in solid organs.

Pulmonary hypertension in sickle-cell disease: comorbidities and echocardiographic findings.

BACKGROUND: Our aim is to determine comorbidities associated with pulmonary hypertension (PHT) in clinically stable sickle-cell disease (SCD) patients and to evaluate left ventricular (LV) and right ventricular (RV) function in those patients. METHODS: Echocardiography was performed in 87 SCD patients that were divided into group I (without PHT) and group II (with PHT). Both groups were compared with healthy controls. RESULTS: A history of retinopathy and leg ulcer was more frequent in group II than group I (p < 0.01). Haemoglobin levels were lower (p < 0.05), whereas blood urea nitrogen, lactate dehydrogenase and total bilirubin levels were higher in group II (p < 0.01). Although group II patients had larger LV end-diastolic, LV end-systolic and RV diastolic diameters compared with group I patients and controls (p < 0.05), LV ejection fraction was similar in the three groups. The mitral peak early diastolic inflow velocity to peak late diastolic inflow velocity (E/A) ratio was similar in group I, group II and the control group. The tricuspid E/A ratio was lower in group II than group I and controls (p < 0.05). CONCLUSION: End organ damage occurs more often and haemolysis is severer in SCD patients with PHT than SCD patients without PHT. Although LV systolic and diastolic function is well preserved, RV diastolic function is disturbed in those patients with PHT.

Increased QT dispersion in sickle cell disease: effect of pulmonary hypertension.

BACKGROUND: QT dispersion has been proposed to be a predictor of adverse outcomes in a variety of cardiac disease states. The objective of this study was to examine QT dispersion in patients with sickle cell disease (SCD) and to assess the effect of pulmonary hypertension (PHT) on QT dispersion. METHODS: We performed Doppler echocardiographic assessments of pulmonary artery systolic pressure in 73 (mean age 18.5 +/- 8.0 years) steady-state SCD patients and 25 (mean age 19.6 +/- 7.2 years) healthy subjects. Resting 12-lead electrocardiogram was recorded and QT dispersion was calculated as the difference between maximum and minimum QT intervals. Bazett's formula was used to obtain a rate-corrected value of the QT interval (QTc). RESULTS: Maximum QTc, minimum QTc and QTc dispersion were significantly increased in SCD patients compared to the control subjects (p < 0.0001, p < 0.05, p < 0.0001, respectively). Among SCD patients, patients with PHT had higher maximum QTc and QTc dispersion than patients without PHT (p < 0.0001). However, minimum QTc showed no significant differences between the two patient groups. CONCLUSION: QTc dispersion is significantly increased in SCD patients, especially those with PHT indicating regional inhomogeneity of ventricular repolarization.

Seroprevalence of hepatitis B and hepatitis C in patients with thalassemia and sickle cell anemia in a long-term follow-up.

BACKGROUND: Transfusion-dependent patients are more prone to acquiring various transfusion-transmitted infections such as hepatitis B (HBV), hepatitis C (HCV) and human immunodeficiency virus (HIV). The aim of the study was to investigate the prevalence of these infections in patients with thalassemia and with sickle cell anemia (SCA) receiving multiple blood transfusions. METHODS: The subjects of the present study were 399 multi-transfused patients with beta-thalassemia major or intermedia and SCA who have been registered at the two regional hemoglobinopathy centers in Turkey since 1996. Hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV) and human immunodeficiency virus antibodies (anti-HIV) tests were assayed by a second-generation enzyme-linked immunosorbent assay method. RESULTS: Of the 399 patients, 3 were HBsAg positive (0.75%), 18 were anti-HCV positive (4.5%), and none was anti-HIV positive. All patients with HBsAg and 14 (77.7 %) patients with HCV received initial blood transfusions before second-generation tests were performed. Patients who were anti-HCV positive had a significantly higher mean number of blood transfusions and peak serum alanine transaminase level than anti-HCV-negative patients. CONCLUSIONS: These results showed that after introduction of more sensitive screening tests and stringent donor selection procedures, incidence of HCV infection was significantly reduced, but there was still a serious risk for HCV infection, and there was a minor risk for HBV infection in patients with thalassemia and SCA.

Right ventricular and pulmonary function in sickle cell disease patients with pulmonary hypertension.

The effects of sickle cell disease (SCD) on right ventricular (RV) and pulmonary function in SCD patients with pulmonary hypertension is not well-known. The aim of this study was to investigate RV and pulmonary functions in patients suffering from SCD with or without pulmonary hypertension using color tissue Doppler imaging and spirometry. We evaluated 48 asymptomatic patients with SCD. All patients underwent echocardiography with tissue Doppler imaging and pulmonary function test. Patients were divided into two groups: Group 1 consisted of 27 patients (age, 18.1 +/- 7.1 years) with normal pulmonary artery pressure, and group 2 consisted of 21 patients (age, 21.4 +/- 7.4 years) with pulmonary hypertension. Both groups were compared with a sex- and age-matched control group including 24 normal healthy subjects (age, 19.8 +/- 9.2 years). Tricuspid lateral annular systolic (S (m)) and early diastolic velocity (E (m)) were higher in group 1 than group 2 and the control group (p < 0.05). Tricuspid lateral annular late diastolic velocities (A (m)), isovolumetric contraction time, and myocardial performance index (MPI) were higher and the E (m)/A (m) ratio was lower in group 2 than group 1 and the control group (p < 0.05). However, no differences were found in the tricuspid lateral annular E (m) deceleration time, ejection time, and isovolumetric relaxation time between group 1, group 2, and the control group. Tricuspid lateral annular S (m) and E (m) were similar in group 2 and the control group. Forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), and the diffusion capacity of the lung for carbon monoxide were decreased in both groups of patients compared to the control group (p < 0.05). However, there was no difference in respiratory rate, FEV(1)/FVC ratio, peak expiratory flow, and total lung capacity between group 1, group 2, and the control group. There were no differences in any indices of lung function between the two groups of patients. MPI is useful index to evaluate RV function in patients with SCD. RV diastolic function was disturbed in only SCD patients with pulmonary hypertension. On the other hand, the restrictive pattern of pulmonary function abnormalities had developed in both groups of patients.

Neurological soft signs as the stroke risk in sickle cell disease.

Sickle cell disease (SCD) is a common form of hemoglobinopathy and is highly prevalent worldwide. Silent cerebral infarction, which represents infarction without clinical signs, is a risk factor for clinical stroke in patients with SCD. It is well known that silent infarction predisposes patients with SCD to overt stroke. The aim of the present study is to investigate the effect of silent infarction on neurological soft signs (NSS), which demonstrate subtle impairments in sensory integration, motor coordination and the sequencing of complex motor acts and to evaluate whether NSS can be used in clinical practice to evaluate the patients at risk of stroke in SCD patients with silent infarction. Fifty-nine SCD patients without any documented history of cerebrovascular accident and 28 healthy controls were included in this study. All the patients with SCD were evaluated with cerebral magnetic resonance imaging. We found that the NSS scores were significantly higher in patients with silent cerebral infarction than those in patients without silent infarction and control subjects (p < 0.05). Importantly, there was no significant difference in the NSS scores between the patients without silent infarction and control subjects. These results indicate that high NSS scores represnt an important finding for diagnosis of silent infarction in SCD patients. As silent infarction increases the risk for stroke in patients with SCD, NSS can be used to provide additional information in diagnosis of the patients with possible stroke risk during the course of SCD.

Co-existince of sickle cell disease and hemidiaphragm paralysis.

Sickle cell anemia is a disease caused by production of abnormal hemoglobin. Infection, acute splenic sequestration crisis, aplastic crises, acute chest syndrome, stroke, cholelithiasis, renal disease and pain are the major complications. Unilateral or bilateral diaphragm paralysis maybe seen following phrenic nerve injury and with a variety of motor-neuron diseases, myelopathies, neuropathies, and myopathies. Prominent right hemi-diaphragma elevation was observed on chest radiograph of a 14 years' old female patient with sickle cell disease. Her medical history yielded neither trauma nor intra-thoracic surgery. She didn't have either motor deficit or sensation disorder on any region of her body. Thorax CT yielded no lesion except the significantly elevated right diaphragm. Her cranial CT showed no lesion, too. Diagnosis of right hemidiaphragm paralysis was confirmed by positive Hitzenberg Sniff test on fluoroscopy. Although several pathophysiologic mechanisms are known to be involved and lead to central neurologic complications in sickle cell disease, involvement of peripheric nerves have not been reported. Here we present a 14 years' old female patient with sickle cell anemia and unilateral diaphragm paralysis, co-existence of which have not been reported so far.