Research discovers new deadly link to sickle cell disease

A new study led by a researcher at Children's Hospital & Research Center at Oakland is the first to find that an amino acid deficiency in sickle cell disease is the result of hemolysis, a process where red blood cells rupture and release their contents into the blood stream. Low availability of the amino acid arginine is associated with lung disease and death in adult sickle cell patients.

The study, published in the July 6th issue of the Journal of American Medical Association (JAMA) supports new therapeutic strategies aimed at increasing arginine levels either through nutritional supplements or by developing new drug therapies that disable the arginase enzyme that consumes arginine.

"Lower amino acid ratios, which indicates low arginine availability, were found in patients who had more severe pulmonary hypertension, a condition involving high blood pressure in arteries carrying blood from the heart to small vessels in the lungs," said Claudia Morris, M.D., an Emergency Department physician and researcher at Children's Hospital Oakland. "This incurable condition is the leading cause of death in adults with sickle cell disease," she added.

The published report in JAMA also highlights important new warning signs that may predict the severity of the disease and could be useful in identifying adult patients at risk for early death through a simple blood test that measures amino acid levels. The study is the result of a multi-center collaboration that includes Dr. Morris as lead investigator, Mark Gladwin, M.D. and Greg Kato M.D. from the National Heart, Lung, and Blood Institute, which is a part of the National Institutes of Health and Sidney Morris Jr., Ph.D from the University of Pittsburgh School of Medicine.

"With this new finding and continued research, we hope to increase our understanding of the development of pulmonary hypertension not only in sickle cell disease, but in thalassemia (Cooleys anemia) and other inherited anemias," said Elizabeth G. Nabel, M.D., director of the National Heart, Lung, and Blood Institute, which co-funded the research.

Dr. Morris and her colleagues published their conclusions after a four-year study of 228 sickle cell patients and 36 controls. Blood was taken from the sickle cell patients to measure amino acids and arginase activity. An ultrasound of their heart and lung vessels was also conducted. A total of 18 patients with sickle cell disease died during the study, 14 of whom had pulmonary hypertension identified at enrollment. Consequently, patients with low amino acid ratios were 3.6 times at greater risk of death than patients with high arginine availability. It is anticipated the findings of this study will provide new insight into diseases associated with hemolysis, and help scientists create new strategies for treating sickle cell anemia.

Children's Hospital Oakland has the country's largest, most innovative sickle cell disease treatment and research programs. Dr. Morris is a clinical scientist at the hospital's research institute with primary investigations into asthma and sickle cell disease. Further studies are needed to establish safety and efficacy of long-term treatment of arginine and other therapies that maximize arginine availability. Dr. Morris is currently seeking funding for such studies.