Slow accrual and no cost extension not approved by NHLBI

This study will evaluate the safety of eptifibatide in sickle cell patients and how well it works during the course of painful crises. The overall hypothesis that we seek to test is that increased platelet activation and the resultant inflammatory responses are important contributors to the problems of sickle cell disease. Sickle cell disease has been referred to both as a condition associated with increased risk of blood clots and increased inflammation. A painful crisis represents the most common cli nical problem in sickle cell disease, but the treatment of these crises remains inadequate.

Sickle cell disease has been referred to both as a condition associated with increased risk of blood clots and increased inflammation. Despite the abundant laboratory evidence of abnormal blood clotting and inflammation, the contribution of these changes to the problems experienced by patients with sickle cell disease remains uncertain. In additional to abnormal blood clotting, platelets (small blood cells that help blood clotting) are more activated in sickle cell disease patients compared to healthy patients without this disease.

In addition, when sickle cell disease patients experience a painful crisis, there is evidence that the platelet activation and abnormal blood clotting increase even further. Activated platelets release a substance called cluster of designation 40 ligand, which can increase how sticky the lining of blood vessels are and can increase the abnormal blood clotting. The level of cluster of designation 40 ligand is much higher in sickle cell disease patients compared to healthy individuals without this disease. In addition, the levels increase even further when sickle cell patients are experiencing a painful crisis.

Painful crisis represent the most common clinical problem in sickle cell disease, and are largely responsible for making the lives of these patients so unpredictable. However, the treatment of these painful crisis remains inadequate, consisting mainly of strong pain medications. In this study, we will evaluate the safety of eptifibatide in sickle cell patients and how well it works during the course of painful crises. At the completion of this trial, we will have an improved understanding of the contribution of platelet activation and inflammation to the problems in sickle cell disease.

The overall hypothesis that we seek to test is that increased platelet activation and the resultant inflammatory responses are important contributors to the problems of sickle cell disease. We believe that by decreasing platelet stickiness, and the release of mediators of inflammation and abnormal blood clotting, eptifibatide will affect the clinical course of complications in this disease.

If the results from our study support the hypothesis that eptifibatide is safe and effective in this population, we plan on carrying out larger studies to more definitively evaluate the safety of eptifibatide and how well it works in the treatment and/or prevention of painful crises in sickle cell disease.

Inclusion Criteria:

1. Age between 18 and 55 years
2. Have confirmed diagnosis of sickle cell anemia or sickle beta zero thalassemia
3. Have a serum creatinine </= 1.2 mg/dl
4. Have serum transaminase values < 3 times upper limits of normal
5. Have a platelet count >/= 150 x 10^9/L
6. Have normal baseline coagulation profile
7. Sudden onset of pain involving one or more sites and typical of usual pain episodes
8. Have adequate intravenous access
9. Be able to understand the requirements of the study and be willing to give informed consent
10. Women of child-bearing age must be practicing (and will continue to practice for the course of the study) an adequate method of contraception (oral contraception, depo-provera, bilateral tubal ligation or barrier method)

Exclusion Criteria:

1. Have a baseline hemoglobin < 6.0 gm/dl
2. Have a history of major gastrointestinal bleeding or a bleeding diathesis
3. Have an ongoing episode of acute chest syndrome
4. Have a past history of clinically overt stroke(s)
5. Have severe hypertension (systolic blood pressure > 200mmHg and/or diastolic BP >110mmHg) not adequately controlled on hypertensive medication
6. Have had major surgery within the six weeks preceding enrollment
7. Are pregnant or breastfeeding
8. Are on chronic anticoagulation or antiplatelet (including non-steroidal anti-inflammatory drugs) therapy
9. Have a history of metastatic cancer
10. Are on a chronic transfusion program or have received a blood transfusion in the prior 8 weeks
11. Have a positive urine toxicology screen for phencyclidine, cocaine or amphetamines.
12. Have a history of alcohol abuse
13. Have received any investigational drugs within the past 4 weeks.

The study was terminated early resulting in small numbers of subjects analyzed.