Date of Award

January 2013

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Farzana D. Pashankar

Subject Area(s)

Medicine

Abstract

Given the morbidity and mortality associated with pulmonary hypertension and progressive renal failure in sickle cell disease, recognition of both organ dysfunctions during childhood should allow for improved management of patients and early treatment for both. The definitive diagnosis of pulmonary hypertension is made on cardiac catheterization, however measurement of tricuspid regurgitant jet velocity (TRV) on echocardiogram can be used to estimate pulmonary artery systolic pressures and can be used as a screening modality for pulmonary hypertension. Pulmonary hypertension is defined as TRV ≥2.5m/sec and occurs in 16-30% of children with sickle cell disease on screening echocardiograms. Two studies were conducted on a cohort of children from the sickle cell program at Yale New Haven Children's Hospital. The first study was conducted to determine the longitudinal natural history of TRV in untreated children with sickle cell disease (N=100 patients). A detailed retrospective chart review was conducted on all sickle cell patients screened with echocardiograms from June 2005 to November 2012. Patients aged 6-21 years were included, 87 with HbSS and 13 with β° thalassemia. At baseline, 67% of patients (N=67) had normal TRV <2.5 m/sec and 33% of patients (N=33) had elevated TRV ≥2.5 m/sec on screening echocardiogram. Follow up echocardiograms were available for 82% of patients (82 of 100), and the median follow up time was 3.59 years. On follow up, 61.40% (N=35) of patients with baseline normal TRV continued to have normal TRV on all subsequent echocardiograms, whereas 38.60% (N=22) of patients had at least 1 echocardiogram with an elevated TRV. Risk factors associated with TRV conversion were baseline low O2 saturation, low hemoglobin and high reticulocyte count (all P <0.05). On follow up, 32% (N=25) of patients with elevated TRV at baseline continued to have elevated TRV on all subsequent echocardiograms, whereas 68% (N=17) of patients had at least 1 echocardiogram with normal TRV without intervention. Risk factors associated with persistent TRV elevation were baseline elevated TRV, low hemoglobin, and high white blood count (all P <0.05). Three of the 100 patients died during the follow up period, one with elevated TRV. A second study was conducted to determine whether elevated TRV was associated with proteinuria in children with sickle cell disease (N=85 patients). A detailed chart review was conducted on sickle cell patients screened with both echocardiograms and urinalysis from June 2005 to July 2010. Longitudinal data from subsequent echocardiograms and urine analyses were also collected. On initial echocardiograms, 32.9% (N=28) had an elevated TRV ≥2.5 m/sec. At initial screening 7.14% (N=2) of these patients with elevated TRV had proteinuria, compared to only 1.75% (N=1) without elevated TRV (P=0.25). On follow up, 19.08% of repeat urinalysis showed proteinuria in patients with elevated baseline TRV compared to 12.35% in patients with normal baseline TRV (P=0.04). Our first study revealed that patients with elevated TRV should be followed longitudinally prior to initiating treatment, as many patients will have normalization of TRV without intervention. The first study also showed that patients with high hemolytic rate as evidenced by low hemoglobin and high reticulocyte count are at high risk of TRV conversion and should be monitored closely. Our second study found a new association between elevated TRV and proteinuria in children with sickle cell disease followed longitudinally.

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