title: Relationship of erythropoietin, fetal hemoglobin, and hydroxyurea treatment to tricuspid regurgitation velocity in children with sickle cell disease.
abstract: Hydroxyurea and higher hemoglobin F improve the clinical course and survival in sickle cell disease, but their roles in protecting from pulmonary hypertension are not clear. We studied 399 children and adolescents with sickle cell disease at steady state; 38% were being treated with hydroxyurea. Patients on hydroxyurea had higher hemoglobin concentration and lower values for a hemolytic component derived from 4 markers of hemolysis (P < or = .002) but no difference in tricuspid regurgitation velocity compared with those not receiving hydroxyurea; they also had higher hemoglobin F (P < .001) and erythropoietin (P = .012) levels. Hemoglobin F correlated positively with erythropoietin even after adjustment for hemoglobin concentration (P < .001). Greater hemoglobin F and erythropoietin each independently predicted higher regurgitation velocity in addition to the hemolytic component (P < or = .023). In conclusion, increase in hemoglobin F in sickle cell disease may be associated with relatively lower tissue oxygen delivery as reflected in higher erythropoietin concentration. Greater levels of erythropoietin or hemoglobin F were independently associated with higher tricuspid regurgitation velocity after adjustment for degree of hemolysis, suggesting an independent relationship of hypoxia with higher systolic pulmonary artery pressure. The hemolysis-lowering and hemoglobin F-augmenting effects of hydroxyurea may exert countervailing influences on pulmonary blood pressure in sickle cell disease.
authors.affiliation: Howard University, Washington, DC 20060, USA. vgordeuk@howard.edu
authors.forename: Victor R
authors.initials: VR
authors.lastname: Gordeuk
authors.forename: Andrew
authors.initials: A
authors.lastname: Campbell
authors.forename: Sohail
authors.initials: S
authors.lastname: Rana
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nouraie
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Niu
authors.forename: Caterina P
authors.initials: CP
authors.lastname: Minniti
authors.forename: Craig
authors.initials: C
authors.lastname: Sable
authors.forename: Deepika
authors.initials: D
authors.lastname: Darbari
authors.forename: Niti
authors.initials: N
authors.lastname: Dham
authors.forename: Onyinye
authors.initials: O
authors.lastname: Onyekwere
authors.forename: Tatiana
authors.initials: T
authors.lastname: Ammosova
authors.forename: Sergei
authors.initials: S
authors.lastname: Nekhai
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Kato
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
authors.forename: Oswaldo L
authors.initials: OL
authors.lastname: Castro
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications / Q000188:drug therapy*; D000986:Antisickling Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004921:Erythropoietin / Q000097:blood*; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis* / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D008297:Male; D014262:Tricuspid Valve Insufficiency / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D055815:Young Adult
chemical_list: D000986:Antisickling Agents; D004921:Erythropoietin; D005319:Fetal Hemoglobin; D006918:Hydroxyurea