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Fetal haemoglobin variations following hydroxyurea treatment in patients with cyanotic congenital heart disease
P Triadou1, M Maier-Redelsperger, R Krishnamoorty
1Laboratoire d'Hématologie, Hôpital Necker-Enfants Malades, Paris, France.
Insights
Hydroxyurea (HU) treatment in cyanotic congenital heart disease (CCHD) patients increased MCV and HbF levels. Individual responses to HU for HbF appear genetically influenced, with no significant toxic effects observed.
Area of Science:
- Hematology
- Pharmacology
- Pediatric Cardiology
Background:
- Cyanotic congenital heart disease (CCHD) presents complex hematological challenges.
- Hydroxyurea (HU) is explored for its potential effects on hematological parameters in CCHD.
- Understanding HU's impact is crucial for managing CCHD patients.
Purpose of the Study:
- To compare hematological features in CCHD patients treated with hydroxyurea (HU) versus those not yet treated.
- To investigate the relationship between HU dosage and changes in Mean Corpuscular Volume (MCV) and Hemoglobin F (HbF).
- To explore the mechanisms behind HbF elevation and individual response variations to HU.
Main Methods:
- Comparative analysis of hematological data from 64 CCHD patients on HU and 43 CCHD patients not on HU.
- Exclusion of patients with subclinical renal dysfunction via plasma creatinine measurement.
- Assessment of MCV, HbF, F-cell production, F-reticulocyte production, and plasma erythropoietin levels.
Main Results:
- Patients on HU showed higher MCV and HbF levels compared to the control group.
- MCV increase was cumulative with HU dosage, while HbF increase was dose-independent.
- HbF response resulted from increased F-cell and F-reticulocyte production, not selective F-cell survival.
- No significant correlation was found between plasma erythropoietin and HbF levels.
- Individual variations in HbF response suggested genetic factors.
- No irreversible toxic effects or malignancies were observed during long-term HU treatment (mean >5 years).
Conclusions:
- Hydroxyurea effectively modifies hematological parameters in CCHD patients, notably increasing HbF.
- The mechanism involves enhanced production of F-cells and F-reticulocytes.
- Genetic factors likely influence individual responses to HU therapy.
- Long-term HU administration appears safe in this CCHD patient cohort, including children.
Abstract:
Haematological features of 64 patients suffering from non operable cyanotic congenital heart disease (CCHD) treated with hydroxyurea (HU) were compared with those of 43 patients suffering from the same disorder who had not yet received this drug. Patients with subclinical renal dysfunction were excluded by measuring plasma creatinine levels. MCV and HbF were higher among patients receiving HU, the increase in MCV being cumulative with HU dosage but the rise in HbF dose independent. HbF response to HU was found to be due to the coordinated increase in F-cell and F-reticulocyte production rather than to a selective survival of F-cells. Absence of a relationship between plasma erythropoietin and HbF levels excluded a dominant role of the former in increasing F-cell production and results determined after doubling the HU dosage or immediately after initiating therapy suggested genetic differences to be responsible for the individual variations in Hb F response. No irreversible toxic effects or malignancies were noted in this series of patients. HU was administered for a relatively long period of time, the mean duration of treatment exceeding 5 years, while the study also included patients below the age of 10 years.