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.

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.

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.

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.