The purpose of this study is to determine how often people with sickle cell anemia develop pulmonary hypertension-a serious disease in which blood pressure in the artery to the lungs is elevated.

Men and women 18 years of age and older with sickle cell anemia may be eligible for this study. Participants will undergo an evaluation at Howard University's Comprehensive Sickle Cell Center in Washington, D.C. or at the National Institutes of Health in Bethesda, Maryland. It will include the following:

• medical history
• physical examination
• blood collection (no more than 50 ml., or about 1/3 cup) to confirm the diagnosis of sickle cell anemia, sickle cell trait or beta-thalassemia (Some blood will be stored for future research testing on sickle cell anemia.)
• echocardiogram (ultrasound test of the heart) to check the pumping action of the heart and the rate at which blood travels through the tricuspid valve.

Following this evaluation, a study nurse will contact participants twice a month for 2 months and then once every 3 months for the next 3 years for a telephone interview. The interview will include questions about general health and recent health-related events, such as hospitalizations or emergency room visits.

Sickle cell anemia is an autosomal recessive disorder and the most common genetic disease affecting African-Americans. Approximately 0.15% of African-Americans are homozygous for sickle cell disease, and 8% have sickle cell trait. Acute pain crisis, acute chest syndrome (ACS), and secondary pulmonary hypertension are common complications of sickle cell anemia. Mortality rates of sickle cell patients with pulmonary hypertension are significantly increased as compared to patients without pulmonary hypertension. Recent studies report up to 40% mortality at 22 months after detection of elevated pulmonary artery pressures in sickle cell patients. Furthermore, pulmonary hypertension is thought to occur in up to 30% of clinic patients with sickle cell anemia.

This study is designed to determine the prevalence and prognosis of secondary pulmonary hypertension in adult patients with sickle cell anemia, and to determine whether genetic polymorphisms in candidate genes contribute to its development.

• Pulmonary Hypertension
• Sickle Cell Anemia

• Collins FS, Orringer EP. Pulmonary hypertension and cor pulmonale in the sickle hemoglobinopathies. Am J Med. 1982 Dec;73(6):814-21.
• Castro O, Brambilla DJ, Thorington B, Reindorf CA, Scott RB, Gillette P, Vera JC, Levy PS. The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease. Blood. 1994 Jul 15;84(2):643-9.
• Castro O. Systemic fat embolism and pulmonary hypertension in sickle cell disease. Hematol Oncol Clin North Am. 1996 Dec;10(6):1289-303. Review.
• Kato GJ, Wang Z, Machado RF, Blackwelder WC, Taylor JG 6th, Hazen SL. Endogenous nitric oxide synthase inhibitors in sickle cell disease: abnormal levels and correlations with pulmonary hypertension, desaturation, haemolysis, organ dysfunction and death. Br J Haematol. 2009 May;145(4):506-13. Epub 2008 Mar 17.

• INCLUSION CRITERIA:

All volunteer subjects must be at least 18 years of age and must be able to provide informed, written consent for participation in this study. Decisional impaired subjects will be included in this study provided that a legally authorized representative provides fully informed consent.

Sickle Cell Patients:

Male and females over 18 years of age.

Diagnosis of sickle cell disease (electrophoretic documentation of SS, SC, or S-beta thallassemia genotype is required).

EXCLUSION CRITERIA:

Sickle Cell Patients:

Hb A-only phenotype and sickle cell trait.

Decisionally impaired subjects without a legally authorized representative who are unable to have a next-of-kin surrogate appointed through the services of an ethics consult.

INCLUSION CRITERIA:

Control Subjects:

Male and females African American subjects over 18 years of age.

Exclusion of sickle cell disease (electrophoretic documentation of hemoglobin A is required).

EXCLUSION CRITERIA:

Control Subjects:

Diagnosis of sickle cell disease (electrophoretic documentation of SS, or SC, or SB thallassemia genotype is requird.

Decisionally impaired subjects without a legally authorized representative who are unable to have a next-of-kin surrogate appointed through the service of an ethics consult.