CHAPEL HILL - An intravenous "blood thinner" widely used in patients with acute coronary syndromes and during coronary artery stent placement appears to be safe in patients with sickle cell disease and may have beneficial anti-inflammatory effects, a small study at the University of North Carolina at Chapel Hill School of Medicine has found.
"We have tested a potentially promising drug in sickle cell patients, and the drug appears to be well tolerated. This gives us the impetus to go ahead with further studies of eptifibatide in these patients," said Dr. Leslie V. Parise, department chair and professor of biochemistry and biophysics at the UNC-Chapel Hill School of Medicine.
The hallmark of sickle cell disease is malformed red blood cells that can cause sudden painful episodes when they block small blood vessels. However, sickle cell patients are also at increased risk of developing multiple other complications, including strokes, lung complications and pulmonary hypertension.
The most frequent manifestations of sickle cell disorders are anemia and pain episodes. The episodic exacerbation of pain, often called "crises," is unpredictable and may occur often in some patients.
The only drug presently approved for the treatment of sickle cell disease is hydroxyurea, which has been shown to reduce the frequency of painful episodes.
Parise emphasized the need for further study. "We did not test this drug in patients who are in crisis, and we cannot recommend that doctors prescribe this drug for sickle cell patients at this time," she said.
The results of the study were published online (Oct. 6) in the British Journal of Haematology.
The researchers gave intravenous infusions of eptifibatide (brand name Integrilin) to four patients with sickle cell anemia who were not experiencing pain episodes. "They did well clinically. They did not experience any deleterious changes in their blood tests or have a pain episode," said coauthor Dr. Kenneth I. Ataga, assistant professor of medicine at UNC-Chapel Hill.
In the current study, blood tests showed that while the patients' liver, kidney and other functions remained at baseline, several indicators of inflammation decreased, including levels of a protein called CD40L known to play a role in inflammation and in blood clotting.
Previous studies conducted by Sheritha Lee a graduate student in Parise's lab showed that patients with sickle cell disease have CD40L levels that are as much as 30 times higher than in patients without the disease. Eptifibatide's known ability to decrease CD40L led the researchers to study whether the drug might help sickle cell patients.
In addition to Lee, Parise, and Ataga, other UNC authors of the study are graduate student Mohamed Zayed of the department of pharmacology; and Dr. Eugene P. Orringer, professor of medicine. Authors from Millennium Pharmaceuticals at the time of the study are Drs. Jeanne M. Manganello and David R. Phillips.
The study was funded by the National Institutes of Health and the American Heart Association.
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