Blood Flow and Pain Crises in People With Sickle Cell Disease

• INCLUSION CRITERIA FOR SUBJECTS WITH SICKLE CELL DISEASE IN PAIN CRISIS:

  1. Age 18 years or older.

  2. Diagnosis of sickle cell anemia:

     1. Diagnosis of sickle cell disease (electrophoresis or HPLC documentation of hemoglobin SS, SC, S-beta-thalassemia or other hemoglobinopathies causing sickle cell disease is required).
     2. Acute onset pain crisis in a distribution typical for that subject, onset within the last 7 days and for which hospitalization and parenteral narcotic pain treatment are required.
  3. Ability to provide informed written consent.

EXCLUSION CRITERIA FOR SUBJECTS WITH SICKLE CELL DISEASE IN PAIN CRISIS:

1. Pregnancy.
2. History of non-trivial injury, burns, surgery or skin ulcers on the arms.
3. Carrier of drug resistant bacteria that normally requires isolation while visiting a hospital.

4. Administration of any of the following drugs within the last 14 days:

   • Phosphodiesterase-5 inhibitors (sildenafil, vardenafil, tadalafil)
   • Endothelin-1 receptor blockers (bosentan, sitaxentan, ambrisentan, tezosentan)
   • Nitric oxide donors (nitroglycerin, nitroprusside, nitrates)
5. Ingestion of caffeine within the 12 hours before the start of the study appointment, or tobacco use within the 30 days before the study appointment.

6. Diagnosis with any of the following chronic diseases or conditions:

   • Uncontrolled high blood pressure (systolic blood pressure must not be greater than 160 mmHg or diastolic blood pressure greater than 90 mmHg)
   • Uncontrolled high cholesterol (total cholesterol must not be greater than 240 mg/dL)
   • Uncontrolled diabetes (must not have both a documented history of diabetes and random blood glucose of greater than 200 mg/dL)
   • Chronic kidney disease (serum creatinine must not be greater than 2 mg/dL)
   • Coronary artery disease
   • Peripheral vascular disease
7. Received a blood transfusion within 7 days of the study procedure.

SICKLE CELL DISEASE SUBJECTS IN STEADY STATE

INCLUSION CRITERIA FOR SUBJECTS WITH SICKLE CELL DISEASE IN STEADY STATE:

1. Age 18 years or older.

2. Diagnosis of sickle cell anemia:

   a.Diagnosis of sickle cell disease (electrophoresis or HPLC documentation of hemoglobin SS, SC, S-beta-thalassemia or other hemoglobinopathies causing sickle cell disease is required).

3. Ability to provide informed written consent.

EXCLUSION CRITERIA FOR SUBJECTS WITH SICKLE CELL DISEASE IN STEADY STATE:

1. Pregnancy.
2. History of non-trivial trauma, burns, surgery or skin ulcers on the arms.
3. Carrier of drug resistant bacteria that normally requires isolation while visiting a hospital.
4. Experience of an acute pain crisis requiring intravenous (IV) narcotics and hospital admission within the last 14 days.
5. Ingestion of caffeine within the 12 hours before the start of the study appointment, or tobacco use within the 30 days before the study appointment.

6. Administration of any of the following drugs within the last 14 days:

   • Phosphodiesterase-5 inhibitors (sildenafil, vardenafil, tadalafil)
   • Endothelin-1 receptor blockers (bosentan, sitaxentan, ambrisentan, tezosentan)
   • Nitric oxide donors (nitroglycerin, nitroprusside, nitrates)

7. Diagnosis of any of the following chronic diseases or conditions: <TAB>

   • Uncontrolled high blood pressure (systolic blood pressure must not be greater than 160 mmHg or diastolic blood pressure greater than 90 mmHg)
   • Uncontrolled high cholesterol (total cholesterol must not be greater than 240 mg/dL)
   • Uncontrolled diabetes (must not have both a documented history of diabetes and random blood glucose of greater than 200 mg/dL)
   • Chronic kidney disease (serum creatinine must not be greater than 2 mg/dL)
   • Coronary artery disease
   • Peripheral vascular disease
8. Received a blood transfusion within 7 days of the study procedure.

HEALTHY CONTROL SUBJECTS

INCLUSION CRITERIA FOR HEALTHY CONTROL SUBJECTS

1. Age 18 years or older.
2. African, of African descent or Hispanic
3. Ability to provide informed written consent.

EXCLUSION CRITERIA FOR HEALTHY CONTROL SUBJECTS

1. Pregnancy.
2. History of non-trivial injury, burns, surgery or skin ulcers on the arms.
3. Carrier of drug resistant bacteria that normally requires isolation while visiting a hospital.

4. Administration of any of the following drugs within the last 14 days:

   • Phosphodiesterase-5 inhibitors (sildenafil, vardenafil, tadalafil)
   • Endothelin-1 receptor blockers (bosentan, sitaxentan, ambrisentan, tezosentan)
   • Nitric oxide donors (nitroglycerin, nitroprusside, nitrates)
5. Ingestion of caffeine in the 12 hours before the start of the study appointment, or used tobacco in the 30 days before the study appointment.

6. Diagnosis with any of the following chronic diseases or conditions:

   • Sickle cell disease <TAB>
   • Uncontrolled high blood pressure (systolic blood pressure must not be greater than 160 mmHg or diastolic blood pressure greater than 90 mmHg)
   • Uncontrolled high cholesterol (total cholesterol must not be greater than 240 mg/dL)
   • Uncontrolled diabetes (must not have both a documented history of diabetes and random blood glucose of greater than 200 mg/dL)
   • Chronic kidney disease (serum creatinine must not be greater than 2 mg/dL)
   • Coronary artery disease
   • Peripheral vascular disease