No abstract

Pulmonary hypertension, diagnosed by Doppler echocardiography, is common in adults with sickle cell disease. It appears to be a complication of chronic hemolysis, is resistant to hydroxyurea therapy, and confers a high risk of death. Therapeutic trials targeting this population of patients are indicated.

CUTE CHEST SYNDROME AND painful episodes are the most common precedents of death in adults with sickle cell anemia (SCA). 1 A randomized, doubleblinded, placebo-controlled trial, the

A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at a 5 0.05 level (P-value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality. Am. J. Hematol. 85:403-408, 2010. V

In 1,814 patients with sickle cell disease who had been transfused, the overall rate of alloimmunization to erythrocyte antigens was 18.6%. The rate of alloimmunization in this group appears to be an explicit function of the number of transfusions received because it increases exponentially with increasing numbers of transfusions. Alloimmunization usually occurred with less than 15 transfusions, although the rate of alloimmunization continued to increase when more transfusions were given. The rate of alloimmunization was less in patients with hemoglobin SC disease and sickle-beta+ thalassemia because these patients had received fewer transfusions. Children less than 10 years old had a slightly lower rate of alloimmunization than patients in other age groups even after correction for the number of transfusions given. Women were more frequently alloimmunized than men; this was largely due to the fact that women received more transfusions than men, but in the age group 16 to 20 years the increase may have been due in part to alloimmunization owing to pregnancy. Forty-five percent of those alloimmunized made antibodies of only one specificity; 17% made four or more antibodies reacting with different antigens. Antibodies to the C and E antigens of the Rh group, the Kell antigen, and the Lewis antigens were most commonly made. These findings may be important in formulating a rational transfusion policy in sickle cell disease.