Patient description: The patient is a 34-year-old African American man with the known history of Sickle cell disease comes to the clinic with severe bone pain. The patient had severe pain in his lower back that radiated to both thighs scored 9 out of 10. The patient has had positive history of sickle cell crises since childhood. He also had the same symptoms in past two weeks treated with oxycodone which was not beneficial to his pain. His PCP sent him to the emergency department to receive intra venous pain modulators. The patient is afebrile within the normal blood pressure. No splenomegaly was detected in the physical exam. He has no positive history of drug allergy. He won't smoke or uses any illicit drugs. The lab study is as bellow: Hgb: 8 g/dl WBC: 10000 /mm3 Plt: 300000 /ml MCV: 106 fL Hemoglobine electrophoresis: 91% HbS 6%HbF 3%HbA2 AST: 22 U/L ALT: 43 U/L Alk P: 53 U/L Ferritin: 1200 ng/ml

Clinical trial eligibility criteria: eligible ages (years): 3.0-20.0,  Chuvash Polycythemia Cerebrovascular Disease Pulmonary Hypertension Sickle Cell Anemia A. For PAH in children and adolescents with SCD: for all participants: 1. The informed consent has been signed by the participant, parent or legal guardian as appropriate. 2. Age of 3 to 20 years. for SCD patients: 1. Diagnosis of sickle cell disease (electrophoretic HPLC documentation of SS, SC, Sb thalassemia or other major sickling phenotype such as SD, SO-Arab or SLepore is required). 2. At least three weeks has elapsed since hospitalization for acute chest syndrome, pain crisis, infection or other complication of SCD. 3. Absence of acute infection, pain crisis, or other acute complication of SCD. (Chronic SCD complications such as stuttering priapism, stable chronic pain and leg ulcers are not reasons for exclusion.) for control participants: 1. Self-described race is African American. 2. Absence of diagnosis of SCD as defined above and subsequent electrophoretic or HPLC documentation. 3. Absence of acute infection, injury, surgery or asthmatic episode  for all participants: 1. Age of less than 3 years or 21 years or more at time of enrollment. 2. Presence of acute infection, pain crisis, injury, surgery, asthmatic episode or other acute complication for SCD patients: 1. Hemoglobin A only phenotype, hemoglobin S trait or hemoglobin C trait. 2. Less than three weeks has elapsed since hospitalization for acute chest syndrome, pain crisis, infection or other complication of SCD for control participants: 1. Self-described ethnicity other than African American. 2. Diagnosis of SCD or electrophoretic or HPLC documentation of major sickling phenotype as described above. B. Angiogenic and vasomotor responses mediated by HIF-regulated pathways in patients with SCD and CP with and without PAH. for all participants: 1. The informed consent has been signed by the participant, parent or legal guardian as appropriate. 2. Age of 3 years or greater. 3. Absence of acute infection, pain crisis, cerebral vascular accident, thrombosis or other acute complication. for SCD or CP patients with PAH: 1. Diagnosis of SCD and electrophoretic or HPLC documentation of SS, SC, Sbeta thalassemia or other major sickling phenotype such as SD, SO-Arab or SLepore OR diagnosis of CP and evidence of homozygosity for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine. 2. At least three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication). 3. ECHO-determined TRV of 2.5 m/sec or greater. for SCD or CP patients without PAH: 1. Diagnosis of SCD and electrophoretic or HPLC documentation of SS, SC, Sb thalassemia or other major sickling phenotype such as SD, SO-Arab or SLepore OR diagnosis of CP and evidence of homozygosity for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine. 2. At least three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication). 3. ECHO-determined TRV less than 2.5 m/sec. 4. Matched by age (plus or minus 2 years), sex and ethnicity to a specific patient with SCD and PAH or CP and PAH enrolled for this same study. for control participants: 1. Absence of diagnosis of SCD as defined above and subsequent electrophoretic documentation. 2. Absence of diagnosis of CP and subsequent documentation of VHL 598 wildtype. 3. At least three weeks has elapsed since hospitalization for illness or surgery. 4. Matched by age (plus or minus 2 years) and sex and ethnicity to a specific patient with SCD and PAH or CP and PAH enrolled for this same study. 5. Absence of diagnosis of PAH, anemia, or polycythemia for all participants: 1. Age of less than 3 years. 2. Presence of a condition associated with secondary PAH other than SCD or CP, such as collagen vascular disease, congenital heart disease, or chronic lung disease. 3. Presence of acute infection, injury, surgery, asthmatic episode, pain crisis, cerebral vascular accident, thrombosis or other acute complication for SCD or CP patients with PAH: 1. Hemoglobin AA only phenotype, hemoglobin S trait, hemoglobin C trait for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine heterozygosity or VHL wildtype. 2. Less than three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication). 3. ECHO-determined TRV less than 2.5 m/sec for SCD or CP patients without PAH: 1. Hemoglobin AA only phenotype, hemoglobin S trait, hemoglobin C trait OR for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine heterozygosity or VHL wildtype. 2. Less than three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication). 3. ECHO-determined TRV greater than or equal to 2.5 m/sec for control participants: 1. Diagnosis of SCD or electrophoretic or HPLC evidence of major sickling phenotype as described above OR diagnosis of CP or for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine homozygosity. 2. ECHO-determined TRV greater than or equal to 2.5 m/sec. C. High throughput microarray and genotyping technologies to identify candidate gene polymorphisms involved in pathologic responses to hypoxia in SCD and CP patients with PAH. for all participants: 1. The informed consent has been signed by the participant, parent or legal guardian as appropriate. 2. Age of 3 years or greater. 3. Absence of acute infection, pain crisis, cerebral vascular accident, thrombosis or other acute complication. for SCD or CP patients with PAH: 1. Diagnosis of SCD and electrophoretic or HPLC documentation of SS, SC, Sb thalassemia or other major sickling phenotype such as SD, SO-Arab or SLepore OR diagnosis of CP and evidence of homozygosity for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine. 2. At least three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication). 3. ECHO-determined TRV of 2.5 m/sec or greater. for SCD or CP patients without PAH: 1. Diagnosis of SCD and electrophoretic or HPLC documentation of SS, SC, Sb thalassemia or other major sickling phenotype such as SD, SO-Arab or SLepore OR diagnosis of CP and evidence of homozygosity for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine. 2. At least three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication). 3. ECHO-determined TRV less than 2.5 m/sec 4. Matched by age (plus or minus 2 years), sex and ethnicity to a specific patient with SCD and PAH or CP and PAH enrolled for this same study. for screening for population prevalence of polymorphisms: 1. Absence of diagnosis of SCD, CP or PAH. 2. Self-described African-American or Chuvash ethnicity for all participants: 1. Age of less than 3 years. 2. Presence of acute infection, injury, surgery, asthmatic episode, pain crisis, cerebral vascular accident, thrombosis or other acute complication for SCD or CP patients with PAH: 1. Hemoglobin AA only phenotype, hemoglobin S trait, hemoglobin C trait OR for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine heterozygosity or VHL wildtype. 2. Presence of a condition associated with secondary PAH other than SCD or CP, such as collagen vascular disease, congenital heart disease, or chronic lung disease. 3. Less than three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication). 4. ECHO-determined TRV less than 2.5 m/sec for SCD or CP patients without PAH: 1. Hemoglobin AA only phenotype, hemoglobin S trait, hemoglobin C trait OR for mutation of the von Hippel-Lindau gene at position 598 from cytosine to thymidine heterozygosity or VHL wildtype. 2. Presence of a condition associated with secondary PAH other than SCD or CP, such as collagen vascular disease, congenital heart disease, or chronic lung disease. 3. Less than three weeks has elapsed since hospitalization for SCD (acute chest syndrome, pain crisis, infection or other complication) or CP (cerebral vascular accident, thrombotic event or other complication). 4. ECHO-determined TRV greater than or equal to 2.5 m/sec