Pulmonary hypertension in children and young adults with sickle cell disease: evidence for familial clustering.
BACKGROUND
Pulmonary hypertension (PHTN) is increasingly recognized as a serious complication of sickle cell disease (SCD). Our objective was to determine the prevalence of PHTN and identify factors associated with PHTN among children and young adults with SCD in Lebanon.


METHODS
From June 2004 to June 2008, 90 patients were studied. Correlation of TRV with LDH, mean corpuscular volume (MCV), fetal hemoglobin (HbF), hydroxyurea use, and G6PD deficiency was performed. Transthoracic Doppler echocardiography was performed during steady-state at each patient's initial visit and yearly thereafter. PHT was defined as a tricuspid regurgitant jet velocity (TRV) > or =2.5 m/sec.


RESULTS
Twenty-seven patients (31.8%) were found to have PHTN. They had significantly higher LDH levels (P = 0.008) and MCV (P = 0.024). There was a higher percentage of patients on hydroxyurea in the group with PHTN (78% vs. 50%, P = 0.015). Furthermore, five children, mean age 9.8 years (range, 6-13 years), with initially normal TRV developed PHTN while on hydroxyurea for at least 3 years, at a mean dose of 19.2 mg/kg/day (range, 14-24). PHTN clustered in families and was found in all members with SCD in 7 of the 21 families studied; they contributed 16 of the 27 patients with PHTN. None of the 21 patients with PHTN were G6PD deficient compared to 4 of 36 without PHTN.


CONCLUSIONS
PHTN was common, associated with increased hemolysis but not G6PD deficiency, and clustered in families. Moreover, PHTN developed despite hydroxyurea therapy in five patients.
Dahoui
Hanane A
HA
Children's Cancer Center of Lebanon, American University of Beirut Medical Center, Beirut, Lebanon.
Hayek
Munya N
MN
Nietert
Paul J
PJ
Arabi
Mariam T
MT
Muwakkit
Samar A
SA
Saab
Raya H
RH
Bissar
Abdallah N
AN
Jumaa
Nidal M
NM
Farhat
Fadi S
FS
Dabbous
Ibrahim A
IA
Bitar
Fadi F
FF
Abboud
Miguel R
MR
D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000188:drug therapy / Q000235:genetics*; D000986:Antisickling Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004452:Echocardiography; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D006976:Hypertension, Pulmonary / Q000209:etiology* / Q000235:genetics* / Q000517:prevention & control; D007861:Lebanon; D008297:Male; D010375:Pedigree; D055815:Young Adult
D000986:Antisickling Agents; D006918:Hydroxyurea