Natural History of Sickle Cell Disease and Other Hemolytic Disorders

Under this study, NIH physicians will evaluate and treat patients with sickle cell disease and other hemolytic disorders (diseases involving damage to red blood cells) in order to learn more about the diseases and the painful attacks and lung complications that are often associated with them. Patients in this study will not receive experimental therapy, but will be given standard medical care. Patients who meet the medical criteria for another NIH protocol may be offered participation in that study, but are not obligated to enroll in it.

Patients 5 years of age and older with known or suspected sickle cell disease, sickle cell trait or another anemia or red blood cell disorder such as thalassemia may be eligible for this study. Participants will be admitted to the NIH Clinical Center as an inpatient or outpatient for evaluation and treatment. In addition to a physical examination, evaluation may include the following types of tests and procedures:

• Routine blood and urine tests, including a 24-hour urine collection
• Blood test for genetic analysis to look for genes that may be relevant to the development of sickle cell anemia or other hemolytic disorders
• X-rays, if needed, to evaluate the patient's condition
• Computerized tomography (CT) scans or magnetic resonance imaging (MRI), or both, as needed to examine the lungs, brain, or heart and to measure blood flow in these organs.
• Echocardiogram (heart ultrasound) to determine if there is high blood pressure in the lungs
• Pulmonary (lung) function tests and cardiopulmonary (heart and lung) exercise test to evaluate breathing and exercise capacity to determine if there are lung or heart problems associated with the patient's condition.
• Heart catheterization to measure blood pressures in the heart and lung blood vessels will be offered if the results of clinical evaluation or echocardiogram suggest the presence of high blood pressure in the lungs. For this procedure, the patient is given a local anesthetic, and a catheter (plastic tube) is inserted into a vein in the arm, thigh, chest, or neck until it passes through the right side of the heart. When the catheter is in place, a tiny balloon at the end of the catheter is inflated, temporarily blocking the blood flow and allowing the physician to measure pressure in the lung artery system.
• Ventilation-perfusion scan to measure breathing and circulation in all areas of the lungs. For the perfusion scan, radioactive albumin is injected into a vein and the patient is placed on a table that is positioned under the scanner. The lungs are scanned to detect the location of the radioactive particles as blood flows through the lungs. The ventilation scan is performed by scanning the lungs while the patient inhales a radioactive gas. A mask is placed over the nose and mouth, and the patient breathes the gas while sitting or lying on the table beneath the arm of the scanner. The gas is breathed out entirely in a matter of minutes and is removed from the room by a special exhaust system.

Patients are offered treatment for high blood pressure in the lungs. The medicines used are approved by the Food and Drug Administration for patients with pulmonary hypertension.

This protocol will permit the evaluation and treatment of subjects with hereditary and acquired hemolytic diseases, to facilitate understanding of the pathogenesis and natural history of vaso-occlusive painful crisis and pulmonary complications of sickle cell disease and related cardiopulmonary complications of other hereditary, acquired and iatrogenic hemolytic disorders. Patients will be evaluated with a medical history and physical examination and routine laboratory studies will be obtained as needed to assess diagnosis, disease activity, and disease complications and to monitor for treatment-related responses and toxicities. Blood can be obtained, with subject's consent, for research studies evaluating gene/protein expression and to evaluate the role of vasodialators, vasoconstrictors, inflammatory and redox stress mediators in this population. Patients identified with pulmonary hypertension will have the option to undergo invasive hemodynamic evaluation and treatment with FDA approved drugs, according to current standards of medical practice, with signed informed consent for all offered procedures. Patients eligible for other research protocols will be offered an opportunity to participate in theses studies by signed informed consent. Apart from such protocols, any medical care recommended or provided to the patient will be consistent with routine standards of practice and will be provided in consultation with the patient's referring physician. The establishment of this protocol will provide a means to evaluate and treat patients, and to generate hypotheses and protocols based on this clinical experience in sickle cell disease and in other acquired or inherited hemolytic anemias.

• Hemoglobin SC Disease
• Hematologic Diseases
• Sickle Cell Anemia
• Hemolytic Anemia

• Gaston MH, Verter JI, Woods G, Pegelow C, Kelleher J, Presbury G, Zarkowsky H, Vichinsky E, Iyer R, Lobel JS, et al. Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. N Engl J Med. 1986 Jun 19;314(25):1593-9.
• Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994 Jun 9;330(23):1639-44.
• [No authors listed] From the Centers for Disease Control and Prevention. Mortality among children with sickle cell disease identified by newborn screening during 1990-1994--California, Illinois, and New York. JAMA. 1998 Apr 8;279(14):1059-60. No abstract available.
• Tumblin A, Tailor A, Hoehn GT, Mack AK, Mendelsohn L, Freeman L, Xu X, Remaley AT, Munson PJ, Suffredini AF, Kato GJ. Apolipoprotein A-I and serum amyloid A plasma levels are biomarkers of acute painful episodes in patients with sickle cell disease. Haematologica. 2010 Sep;95(9):1467-72. Epub 2010 Apr 7.
• Olnes M, Chi A, Haney C, May R, Minniti C, Taylor J 6th, Kato GJ. Improvement in hemolysis and pulmonary arterial systolic pressure in adult patients with sickle cell disease during treatment with hydroxyurea. Am J Hematol. 2009 Aug;84(8):530-32. No abstract available.

• INCLUSION CRITERIA:

Patients with sickle cell disease and other hemolytic disorders will be evaluated at the NIH CCMD/NHLBI/NIDDK sickle cell clinic or day hospital. Patients will not be recruited or selected with reference to age, race or gender. The patient population is expected, however, to be predominantly minority in composition (mainly African-American and Latino, with some Asian, European and Native American patients as well) as function of demographics and genetics of these diseases. Children may be evaluated or treated in this protocol with parental informed consent and assent of the child when appropriate.

• Known or suspected sickle cell disease and other hereditary hemolytic disorders such as thalassemia, hereditary sphyerocytosis.
• Immune or other acquired hemolytic states, such as paroxysmal nocturnal hemoglobinuria.
• Iatrogenic hemolytic states (e.g. post-cardiopulmonary bypass or post-transfusion).
• Over 5 years of age (all ages).
• Willingness and capacity to provide informed consent or appropriate informed consent from parent or legal guardian.

EXCLUSION CRITERIA:

-Any concurrent condition (medical, social, behavioral) which in the opinion of the research team would preclude or confound acquisition/interpretation of data or delivery of clinical care.