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 ≤ .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 ≤ .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.

Tricuspid regurgitant jet velocity and hospitalization in Tanzanian children with sickle cell anemia

“…LDH may not be specific to hemolysis, 13 and was similar between the groups and not associated with TRV category. This is in contrast to the PUSH study 5,14,15 in which all assessed hemolytic markers were associated with TRV over 2.6 m/s (unconjugated bilirubin not reported) but in line with two smaller studies. 7,9 In a study of adolescent and adult Nigerian patients, combined 16 LDH, but not total bilirubin (unconjugated bilirubin not reported) was associated with elevated TRV.…”

Pediatric Pulmonary Hypertension

“…611 However, there is a suggestion that hydroxyurea, a current therapy that decreases hemolysis, may be associated with an increased risk of PH. 612 For patients with SCD who have PH that is confirmed by cardiac catheterization, we recommend against PAH-targeted therapy except for those with high PVR and normal pulmonary capillary wedge pressure. In these patients, we recommend a trial of either a PGI 2 analog or an ERA.…”

Vascular risk assessment in patients with sickle cell disease

“…28,[30][31][32][33] The Pulmonary Hypertension and the Hypoxic Response in Sickle Cell Disease (PUSH) study is currently being conducted to evaluate this population prospectively; an interim analysis of the first 399 SCD patients between the ages of 3 and 20 enrolled suggests a slightly lower prevalence (22%) of TRV elevation above 2.5m/sec. 19,34,35 However, based on the mean TRV plus two standard deviations in age-and gender-matched control children, the PUSH study has defined an elevated TRV in children as 2.6 m/sec or above. Using this definition, the prevalence of an elevated TRV is actually 11% in the PUSH study.…”