Pulmonary Hypertension in Children with Sickle Cell Disease: Clinical Characteristics and Co-Morbidities.

Abstract

BACKGROUND: Pulmonary hypertension is a potentially life threatening complication described in adults with sickle cell disease and other hemolytic disorders. There has been little to no information on the occurrence of this condition in pediatric patients.METHODS: Retrospective case review of sickle cell patients at Children's Hospital of Pittsburgh to determine the clinical characteristics and co-morbidities of patients previously diagnosed with pulmonary hypertension, as detected by tricuspid regurgitant (TR) jet velocity of ≥ 2.5 m/sec on Doppler echocardiography.RESULTS: Nine patients with sickle cell disease (all HbSS) were diagnosed with pulmonary hypertension, with an initial mean TR jet velocity of 2.98±0.19 m/sec. All had some history of respiratory disease, 4 had a cerebrovascular disease, and 4 were previously on a chronic transfusion program. Laboratory results reveal low hemoglobin, reticulocytosis, and elevated total bilirubin and lactate dehydrogenase in a majority of patients, suggesting clinically significant chronic hemolysis. Therapy initiated for these patients included increasing transfusion therapy, oxygen supplementation, hydroxyurea, and tonsillectomy when indicated. These interventions resulted in a reduction in mean post-therapy TR Jet to 2.61±0.21 m/sec (p=0.0015) in 8 of 9 patients.CONCLUSIONS: Pulmonary hypertension occurs in children with sickle cell disease and is associated with manifestations of increased hemolysis and co-morbid respiratory or cerebrovascular diseases. Aggressive sickle cell-directed therapy and management of co-morbidities reduces the degree of pulmonary hypertension.Table IPt #/Age/SexComplications/Co-morbiditiesHemoglobin% ReticulocytesFerritinTotal BilirubinLDHTherapies/Intervention1: 13/FAsthma, OSA, MCA stenosis, pneumonia/ACS, iron overload8.714.420108.1n/aChronic TRX, asthma therapy, Tonsillectomy2: 18/MACS (multiple), hyperhemolysis, allosensitization, aplastic crises, central hypopnea, cor pulmonale5.8347746.4527Chronic TRX, O2 at night, initiation of hydroxyurea3: 14/MAsthma, nocturnal enuresis, constipation, OSA, ACS, recurrent VOC8.811.143302657Periodic TRX, O2 at night, hydroxyurea, asthma therapy4: 18/MAsthma, Hepatitis C, silent stroke, Moya-Moya syndrome, priaprism, sepsis (multiple), aplastic crises, iron overload9.17.343852.6n/aChronic TRX, O2 at night, asthma therapy5: 17/FHepatitis C, asthma, restrictive lung disease, chronic dyspnea, blain gliosis, silent stroke, ACS, cardiomegaly, allosensitization7.119.7n/a5.7n/aInfrequent TRX (due to allosensitization), O2, asthma therapy6: 12/MAsthma, nocturnal enuresis, sepsis7.9173105.1485Increased frequency TRX, asthma therapy7: 16/MACS, stroke, intracranial hemorrhage8.29.520123.5440Chronic TRX, O2 at night8: 14/FACS, cardiomegaly8.814n/a3.9n/aInitiaion of TRX, O2 at night9: 9/MTonsillar hypertrophy, possible OSA, cardiomegaly6.120.7n/a4.1667Increased frequency TRXAbbreviations: LDH, lactate dehydrogenase; MCA, middle cerebral artery; OSA, obstructive sleep apnea; TRX, transfusion therapy; O2, oxygen; ACS, acute chest syndrome; VOC, vasoocclusive crisisTable IIPatient #Maximum TR JetTR Jet Post-Therapy12.62.4232.733242.82.653.32.863.53732.7832.792.65n/a yetTR Jet: tricuspid regurgitant jet velocity (m/sec)