Pulmonary Hypertension in Sickle Cell Disease: A Common Complication for Both Adults and Children.
Authors: Morris Claudia R. , Gardner Jennifer , Hagar Ward , Vichinsky Elliott P. 
Published: October 2019

Abstract
Pulmonary hypertension (PHT) is a risk factor for death in adults with sickle cell disease (SCD). Although occurring in >30% of adult patients, routine screening is not yet standard of care, and many patients are undiagnosed and untreated. Little is known on the prevalence of PHT in the pediatric population. A retrospective chart review was performed on 362 patients to evaluate screening practices and prevalence of PHT in both adults and children with SCD. Thirty percent (n=110) were < 18 years old, and gender was equally distributed. This review identified 96 patients with PHT (TRjet ≥2.5 m/sec by echo), suggesting a prevalence of 26.5%. However, since only 57% were screened by echo, this prevalence is grossly underestimated. Many echos documenting a TRjet ≥2.5 m/sec were interpreted by a cardiologist as NOT having PHT, likely because abnormal PAP in SCD are lower than in primary PHT. Of patients screened by echo, 46% had PHT (75 SS, 13 SC, 8 Sb-thal). Only 51% were identified by a clinician as having PHT, and only 4% were receiving treatment (chronic transfusion). Fifteen children had PHT. While 11 carried the diagnosis, none were on therapy. There was no difference in the percentage of adults vs. children screened by echo, however 56% of adults screened had PHT compared to 25% of children screened. Patients screened by echo were more likely to be male, homozygous for SS and were generally a sicker population. Patients found to have PHT were older (r=0.22, p<0.0001), and had a higher incidence of asthma, VOC episodes, gallbladder and renal disease, hepatitis C, smoking, alcohol and/or drug abuse, >LFTs, >creatinine, and more were on oxygen and/or hydroxyurea therapy compared to those without PHT. Surprisingly, history of ACS and splenectomy was similar in both groups. Comparing adults to children with PHT, more men than women were affected among adults (however more men were screened), while gender was equally distributed among children. Age of children with PHT ranged from 7–17 years (mean 12.6±3 years). Children were more likely to be homozygous for SS (14/15), carry the diagnosis of PHT, have a history of ACS (93% vs. 52%), and a higher incidence of sepsis (40% vs. 14%) than their adult counterparts. However they had fewer complications overall; renal and liver disease was rare, and less were transfused. Compared to children who do not have PHT, kids with PHT are more likely to have a history of ACS (93% vs. 63%), an abnormal CXR (87% vs. 57%), asthma (33% vs. 15%), >VOC events (60% vs. 39%), history of sepsis (40% vs. 9%), but less stroke (7% vs. 17%) and less transfusions including chronic transfusion (27% vs. 50%). It is possible that early transfusion secondary to a CNS event is protective against the development of PHT in children. Stepwise logistical regression modeling included renal disease, chronic transfusion, liver disease and alcohol use as significant risk factors for PHT (ROC = 0.82). Current mortality rate is 2% for patients without PHT vs. 8% for the PHT group (p=0.03). In conclusion, PHT is a common complication in SCD that affects both adults and children. The diagnosis is often missed, even with echo evidence of PHT. In this population 96% were untreated. Children with PHT have a different profile of complications than adults with PHT, suggesting alternate mechanisms of disease pathogenesis in children. Since PHT is associated with high mortality and morbidity, universal screening by echo and increased awareness is essential to identify patients at risk, and new therapies are critically needed.