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 I
Pt #/Age/SexComplications/Co-morbiditiesHemoglobin% ReticulocytesFerritinTotal BilirubinLDHTherapies/Intervention
Abbreviations: LDH, lactate dehydrogenase; MCA, middle cerebral artery; OSA, obstructive sleep apnea; TRX, transfusion therapy; O2, oxygen; ACS, acute chest syndrome; VOC, vasoocclusive crisis 
1: 13/F Asthma, OSA, MCA stenosis, pneumonia/ACS, iron overload 8.7 14.4 2010 8.1 n/a Chronic TRX, asthma therapy, Tonsillectomy 
2: 18/M ACS (multiple), hyperhemolysis, allosensitization, aplastic crises, central hypopnea, cor pulmonale 5.8 34 774 6.4 527 Chronic TRX, O2 at night, initiation of hydroxyurea 
3: 14/M Asthma, nocturnal enuresis, constipation, OSA, ACS, recurrent VOC 8.8 11.1 4330 657 Periodic TRX, O2 at night, hydroxyurea, asthma therapy 
4: 18/M Asthma, Hepatitis C, silent stroke, Moya-Moya syndrome, priaprism, sepsis (multiple), aplastic crises, iron overload 9.1 7.3 4385 2.6 n/a Chronic TRX, O2 at night, asthma therapy 
5: 17/F Hepatitis C, asthma, restrictive lung disease, chronic dyspnea, blain gliosis, silent stroke, ACS, cardiomegaly, allosensitization 7.1 19.7 n/a 5.7 n/a Infrequent TRX (due to allosensitization), O2, asthma therapy 
6: 12/M Asthma, nocturnal enuresis, sepsis 7.9 17 310 5.1 485 Increased frequency TRX, asthma therapy 
7: 16/M ACS, stroke, intracranial hemorrhage 8.2 9.5 2012 3.5 440 Chronic TRX, O2 at night 
8: 14/F ACS, cardiomegaly 8.8 14 n/a 3.9 n/a Initiaion of TRX, O2 at night 
9: 9/M Tonsillar hypertrophy, possible OSA, cardiomegaly 6.1 20.7 n/a 4.1 667 Increased frequency TRX 
Pt #/Age/SexComplications/Co-morbiditiesHemoglobin% ReticulocytesFerritinTotal BilirubinLDHTherapies/Intervention
Abbreviations: LDH, lactate dehydrogenase; MCA, middle cerebral artery; OSA, obstructive sleep apnea; TRX, transfusion therapy; O2, oxygen; ACS, acute chest syndrome; VOC, vasoocclusive crisis 
1: 13/F Asthma, OSA, MCA stenosis, pneumonia/ACS, iron overload 8.7 14.4 2010 8.1 n/a Chronic TRX, asthma therapy, Tonsillectomy 
2: 18/M ACS (multiple), hyperhemolysis, allosensitization, aplastic crises, central hypopnea, cor pulmonale 5.8 34 774 6.4 527 Chronic TRX, O2 at night, initiation of hydroxyurea 
3: 14/M Asthma, nocturnal enuresis, constipation, OSA, ACS, recurrent VOC 8.8 11.1 4330 657 Periodic TRX, O2 at night, hydroxyurea, asthma therapy 
4: 18/M Asthma, Hepatitis C, silent stroke, Moya-Moya syndrome, priaprism, sepsis (multiple), aplastic crises, iron overload 9.1 7.3 4385 2.6 n/a Chronic TRX, O2 at night, asthma therapy 
5: 17/F Hepatitis C, asthma, restrictive lung disease, chronic dyspnea, blain gliosis, silent stroke, ACS, cardiomegaly, allosensitization 7.1 19.7 n/a 5.7 n/a Infrequent TRX (due to allosensitization), O2, asthma therapy 
6: 12/M Asthma, nocturnal enuresis, sepsis 7.9 17 310 5.1 485 Increased frequency TRX, asthma therapy 
7: 16/M ACS, stroke, intracranial hemorrhage 8.2 9.5 2012 3.5 440 Chronic TRX, O2 at night 
8: 14/F ACS, cardiomegaly 8.8 14 n/a 3.9 n/a Initiaion of TRX, O2 at night 
9: 9/M Tonsillar hypertrophy, possible OSA, cardiomegaly 6.1 20.7 n/a 4.1 667 Increased frequency TRX 
Table II
Patient #Maximum TR JetTR Jet Post-Therapy
TR Jet: tricuspid regurgitant jet velocity (m/sec) 
2.6 2.4 
2.7 
2.8 2.6 
3.3 2.8 
3.5 
2.7 
2.7 
2.65 n/a yet 
Patient #Maximum TR JetTR Jet Post-Therapy
TR Jet: tricuspid regurgitant jet velocity (m/sec) 
2.6 2.4 
2.7 
2.8 2.6 
3.3 2.8 
3.5 
2.7 
2.7 
2.65 n/a yet 

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