Alpha thalassemia allelic frequency in Lebanon.

BACKGROUND: Hemoglobinopathies are the most common reported monogenic disorders worldwide. It is well established that Mediterranean and Arab countries are high risk areas for thalassemia in general, and for alpha thalassemia in particular. Reports of alpha thalassemia gene mutations from the Lebanese population are limited. PROCEDURE: We investigated the spectrum of alpha thalassemia mutations in a sample of 70 unrelated Lebanese families. Six different mutations of alpha thalassemia gene were identified. RESULTS: The most prevalent mutations were the single gene deletion -α(3.7) (43%) and the non-gene deletion α2 IVS1 [-5nt] (37%). The double deletional determinant -(MED) was detected only in 14% of thalassemic chromosomes. CONCLUSION: We determined the mutational spectrum of alpha thalassemia which might be used in the future for molecular investigations of the disease in susceptible patients in our population.

Pulmonary hypertension in children and young adults with sickle cell disease: evidence for familial clustering.

BACKGROUND: Pulmonary hypertension (PHTN) is increasingly recognized as a serious complication of sickle cell disease (SCD). Our objective was to determine the prevalence of PHTN and identify factors associated with PHTN among children and young adults with SCD in Lebanon. PROCEDURE: From June 2004 to June 2008, 90 patients were studied. Correlation of TRV with LDH, mean corpuscular volume (MCV), fetal hemoglobin (HbF), hydroxyurea use, and G6PD deficiency was performed. Transthoracic Doppler echocardiography was performed during steady-state at each patient's initial visit and yearly thereafter. PHT was defined as a tricuspid regurgitant jet velocity (TRV) > or =2.5 m/sec. RESULTS: Twenty-seven patients (31.8%) were found to have PHTN. They had significantly higher LDH levels (P = 0.008) and MCV (P = 0.024). There was a higher percentage of patients on hydroxyurea in the group with PHTN (78% vs. 50%, P = 0.015). Furthermore, five children, mean age 9.8 years (range, 6-13 years), with initially normal TRV developed PHTN while on hydroxyurea for at least 3 years, at a mean dose of 19.2 mg/kg/day (range, 14-24). PHTN clustered in families and was found in all members with SCD in 7 of the 21 families studied; they contributed 16 of the 27 patients with PHTN. None of the 21 patients with PHTN were G6PD deficient compared to 4 of 36 without PHTN. CONCLUSIONS: PHTN was common, associated with increased hemolysis but not G6PD deficiency, and clustered in families. Moreover, PHTN developed despite hydroxyurea therapy in five patients.

Venous sinus thrombosis leading to stroke in a patient with sickle cell disease on hydroxyurea and high hemoglobin levels: treatment with thrombolysis.

A 21-year-old man with homozygous sickle cell disease maintained on hydroxyurea for 1 year developed thrombosis of the superior sagittal, right transverse, and right sigmoid dural sinuses with a large venous infarct. He was successfully treated with endovascular thrombolysis. Investigation did not reveal any inherited or acquired hypercoagulable state. This patient however had consistently elevated hemoglobin levels both at the time of the initial event and on follow up. One year later he developed symptomatic avascular necrosis of the right hip. High hemoglobin levels resulting from hydroxyurea therapy may have contributed to development of complications in this patient.

Spontaneous splenic rupture in a patient with factor XIII deficiency and a novel mutation.

We report a novel mutation in factor XIIIA gene that caused severe congenital factor XIII deficiency in a 6 year and 8 month old male. The mutation is a GA deletion in the core domain leading to a premature stop at codon 502. The child had severe deficiency with two episodes of intracerebral hemorrhage. He also developed spontaneous splenic rupture, an unusual complication of this disorder.

Familial infantile pyknocytosis in association with pulmonary hypertension.

Infantile pyknocytosis is a rare condition characterized by transient neonatal hemolytic anemia associated with increased pyknocyte count on blood smear. We describe three siblings with infantile pyknocytosis, born to consanguineous parents. The first and third siblings had neonatal hemolytic anemia that resolved spontaneously at 6 months. The second sibling presented at 11 days with severe hemolytic anemia along with pulmonary hypertension. He died at 39 days from sepsis. The findings support a possible autosomal recessive inheritance. We hypothesize that pulmonary hypertension may be secondary to or aggravated by neonatal hemolysis.

Vitamin D deficiency in sickle cell disease patients in the Eastern Province of Saudi Arabia.

BACKGROUND: Vitamin D deficiency (VDD) is a major global health problem. In sickle cell disease (SCD), VDD is highly prevalent, reaching up to 96% of populations. VDD may contribute to many of the complications of SCD. OBJECTIVE: Estimate the 25-hydroxyvitamin D [25(OH)D] level and the frequency of VDD and insufficiency among among SCD patients by age group and disease status. DESIGN: Analytical cross-sectional. SETTING: Ministry of Health (MOH) secondary care hospital. PATIENTS AND METHODS: Non-probability purposive sampling was used to select SCD patients, aged 12 years and older, of both sexes, who had visited the hospital during a period of 5 years (2010-2014). Blood samples were processed by electrochemiluminescence technology. MAIN OUTCOME MEASURE(S): 25(OH)D levels by demographic data, and disease activity. SAMPLE SIZE: 640 patients. RESULTS: Of those, 82% (n=523) had suboptimal 25(OH)D (0-<30 ng/ mL), and 67% were deficient (0-<20 ng/mL). Patients with any SCD crisis (20.7%, 144/694) had lower 25(OH)D (median, IQR: 10.1 ng/mL [8.6] ng/mL) compared to patients without crisis (71.0%, 493/694) (15.7 ng/ mL [18.2] ng/mL) (P<.001). Deficiency was more common in the young.er age groups and in sickle cell anemia patients with crisis. CONCLUSIONS: VDD is highly prevalent in this population. Established vitamin D screening is a necessity, so that affected patients can be treated. LIMITATIONS: Presence of residual confounders such as nutritional status, physical activity, lack of sun exposure, medications that alleviate SCD crises (such as hydroxyurea), and comorbid illnesses. The relationship between sickle cell disease genotype and vitamin D level was not analyzed. CONFLICT OF INTEREST: None.

Acute respiratory distress associated with external jugular vein catheterization in the newborn.

We report on the acute onset of respiratory distress secondary to fluid accumulation in the chest within hours of placement of an external jugular venous line in a newborn. External jugular venous catheterization in the newborn is a procedure with potentially serious complications, and should be avoided unless the patient is monitored closely.

Hydroxyurea in sickle cell disease patients from Eastern Saudi Arabia.

OBJECTIVE: To assess the efficiency and safety of hydroxyurea in patients with sickle cell disease from the Eastern Province, Kingdom of Saudi Arabia. METHODS: The study was an open-label and uncontrolled trial. Patients older than 10 years of age with sickle cell disease who suffered 4 or more episodes of painful vaso-occlusive crises requiring admissions per year were included, 36 patients (23 males and 13 females) were included between June 1994 and June 1998. Patients were started on hydroxyurea at a dose of 8-10mg/kg per day and the dose was escalated to a maximum tolerated dose or a dose of 35 mg/kg per day. Blood count, renal and liver functions, and hemoglobin F levels were monitored regulary. Clinical response was assessed by record of number of vaso-occlusive crises, requirement for hospital admission and self scoring at the end of each year of treatment. RESULTS: Thirty-six patients were enrolled in the study until the time of analysis of the data. The data of the first 27 patients (18 males and 9 females) who completed 12 months of therapy were analyzed and presented. There was significant reduction in leukocyte, platelet counts and rise in total hemoglobin and hemoglobin F. Hemoglobin F rose by 1.2-13 folds, from the baseline. Seventy-four percent of patients had at least 2 fold rise of maximum hemoglobin F. The mean maximum tolerated dose of hydroxyurea was 16.4 mg/kg. There was significant reduction in hospital admissions and hospital stay. No major side effects had occured. CONCLUSION: Hydroxyurea seems to be effective in decreasing the frequency of vasooclusive crises in patient with sickle cell disease from Eastern Saudi Arabia. In this preliminary analysis no major side effects were observed. Long term side effects need to be monitored.

Acute chest syndrome in sickle cell disease in Saudi Arab Children in the Eastern Province.

BACKGROUND: This study was conducted to define the clinical features and outcome of acute chest syndrome (ACS) in sickle cell disease (SCD) patients in the Eastern Province of Saudi Arabia. PATIENTS AND METHODS: This was a prospective study involving patients who were 12 years or younger, admitted to Qatif Central Hospital with ACS (or developed ACS during hospitalization) between July 1992 and July 1997. Chest x-ray, CBC, cultures (blood, sputum and throat), mycoplasma titers and blood gases were performed at the onset of ACS. Oxygen therapy, antibiotics, blood transfusion and mechanical ventilation were used as required. RESULTS: One hundred and thirty-two patients with episodes of ACS (154 admissions which accounted for 7.7% of SCD admissions) were studied. Fever, cough and chest pain were the most common symptoms. Raised temperature, tachypnea and tachycardia were the most common findings. ACS was associated with painful crisis (46.8%) and infections (13%). It was mild in 31.2%, moderate in 57.1% and severe in 11.7% of admissions. Radiological studies revealed unilateral infiltrate in 69.5%, bilateral infiltrate in 20.8% and pleural effusion in 3.3%. There was a significant drop in Hb and platelets, and a rise in WBC. Significant hypoxia was found in 10.4% and bacteremia was found in 7.1%. Cephalosporine was required for 37%, simple blood transfusion for 74%, exchange transfusion for 2%, and mechanical ventilation for 0.7% of admissions. None of our patients died. Mean duration of hospitalization was 6.7 days. CONCLUSION: Acute chest syndrome in children with sickle cell disease in the Eastern Province of Saudi Arabia is relatively mild and infrequent, and rarely associated with bacteremia.

Acute chest syndrome.

Acute chest syndrome is an acute pulmonary illness in patients with sickle cell disease. It is a common problem, causing significant morbidity and mortality. Many factors may cause this syndrome. Treatment is primarily supportive. Therapy includes hydration, analgesia, supplemental oxygen, antibiotics, blood transfusion and mechanical ventilation. Early detection and aggressive management may limit its severity and prevent its complications. This article reviews the current information for its definition, frequency, pathogenesis, clinical features, complications, investigations, management and prevention. Recent advances in management of acute and recurrent attacks will be discussed.

Massive splenic infarction in Saudi patients with sickle cell anemia: a unique manifestation.

Splenic infarcts are common in patients with sickle cell anemia (SCA), but these are usually small and repetitive, leading ultimately to autosplenectomy. Massive splenic infarcts on the other hand are extremely rare. This is a report of our experience with 8 (4 males and 4 females) cases of massive splenic infarction in patients with SCA. Their ages ranged from 16 to 36 years (mean 22 years). Three presented with left upper quadrant abdominal pain and massive splenic infarction on admission, while the other 5 developed massive splenic infarction while in hospital. In 5 the precipitating factors were high altitude, postoperative, postpartum, salmonella septicemia, and strenuous exercise in one each, while the remaining 3 had severe generalized vasoocclusive crises. Although both ultrasound and CT scan of the abdomen were of diagnostic value, we found CT scan more accurate in delineating the size of infarction. All our patients were managed conservatively with I.V. fluids, analgesia, and blood transfusion when necessary. Diagnostic aspiration under ultrasound guidance was necessary in two patients to differentiate between massive splenic infarction and splenic abscess. Two patients required splenectomy during the same admission because of suspicion of secondary infection and abscess formation, while a third patient had splenectomy 2 months after the attack because of persistent left upper quadrant abdominal pain. In all the 3 histology of the spleen showed congestive splenomegaly with massive infarction. All of our patients survived. Two patients subsequently developed autosplenectomy while the remaining 3 continue to have persistent but asymptomatic splenomegaly. Massive splenic infarction is a rare and unique complication of SCA in the Eastern Province of Saudi Arabia, and for early diagnosis and treatment, physicians caring for these patients should be aware of such a complication.

Clinical presentation and treatment outcome of children with Burkitt lymphoma in Lebanon: a single institution's experience.

The authors reviewed the medical records of 42 children younger than 13 years of age diagnosed with Burkitt lymphoma at the American University of Beirut Medical Center between 1983 and 1993. The male:female ratio was 3.9. The abdomen was the most common site of disease (86%). Jaw, central nervous system, and bone marrow involvement occurred in 16.6%, 16.6%, and 9.5%, respectively. The mean LDH level was 447 U/L. The mean age at diagnosis was 6.9 years. Thirty-nine patients received a variation of the COMP protocol. The total duration of treatment ranged from 6 to 18 months. At a median follow-up of 5 years the event-free survival was 100% for children with stages I and II disease, 77.4% (+/- 2 SE) for stage III, and 0% for stage IV. Failures in stage III patients were due to tumor lysis (3/24) and progressive disease (2/24). Aggressive therapy with high doses of methotrexate and anthracyclines may not be necessary for the treatment of children with extensive abdominal disease (stage III) in Lebanon. If confirmed in a larger series of patients, this study could have a major impact on the treatment of Burkitt lymphoma in Lebanon and other countries with limited resources.

Are we underestimating the leukemogenic risk of hydroxyurea.

Hydroxyurea is an established drug that has been used for the treatment of myeloproliferative disorders and some solid tumors for some time. In recent years it has also been found to be effective in the treatment of sickle cell disease. Short term side effects are not serious, and are manageable. The major concern is the potential leukemogenesis with long term use. The risk of leukemogenesis is not defined with its use in benign hematological conditions. We report a case of acute myeloid leukemia with no preceding myelodysplastic syndrome, occurring after 2 years of hydroxyurea therapy in a patient with sickle cell disease.