Pulmonary Artery Occlusion Pressure May Overdiagnose Pulmonary Artery Hypertension in Sickle Cell Disease

Abstract Background Studies in adults with sickle cell disease (SCD) suggest an increased prevalence of pulmonary artery hypertension (PAHTN) with associated increased morbidity and mortality. These findings have not been validated in children. Methods The digital echocardiography (echo) database at Children’s National Medical Center was searched for echos performed on patients with SCD from 1999 to 2006. Patients on chronic transfusions undergo regularly scheduled studies; other patients are referred for a variety of indications including murmurs, cardiomegaly, hypoxia, chest pain, and respiratory distress. Echo reports and digital images were reviewed and the following information was recorded: Chronic transfusion, date of study, blood pressure, cardiac structure, ventricular function, presence of tricuspid regurgitation (TR), and velocity of TR. The estimated right ventricular (RV) pressure was calculated using modified Bernoulli equation (adding 5 mm Hg for estimated right atrial pressure if the inferior vena cava was not dilated). The ratio of RV systolic pressure to systemic systolic blood pressure was calculated. All studies with TR velocities of < 3 m/sec or a RV to systemic ratio of less than one third were considered to be normal. Results: The SCD database has 1060 patients ages 0 to 21 years; 166 echos were performed in 104 routine patients and 72 echos in 47 children while on chronic transfusions. TR could be measured in 56 routine and 20 transfusion studies. Comorbidities were present in 11 studies (7 patients) in the routine group: structural heart disease (4 ), constrictive pericarditis (1 ), significant obstructive airway disease (1 ), and pneumonia requiring mechanical ventilation (1 ). There were no comorbidities in the transfusion group. The mean TR velocity, estimated RV pressure, and RV to systemic pressure ratios were higher in the routine group; however when patients with comorbidities were removed, this difference was no longer statistically significant. Routine (n=55) Routine/no comorbidities (n=44) Transfused (n=20) 1p = 0.01 transfused vs. routine; p = 0.11 transfused vs. routine/no comorbidities 2p < 0.01 transfused vs. routine; p = 0.09 transfused vs. routine no comorbidities 3p = 0.01 transfused vs. routine; p = 0.13 transfused vs. routine/no comorbidities 1TR velocity (m/sec) 2.54 ± 0.48 2.30 ± 0.30 2.30 ± 0.30 Range 1.67–3.93 Range 1.67–3.19 Range 1.70–2.76 2RV pressure (mm Hg) 31.8 ±10.5 29.2 ± 6.6 26.5 ± 5.6 Range 16.2–67.8 Range 16.2–45.7 Range 16.6–36.4 3RV/systemic pressure ratio 0.29 ± 0.11 0.26 ± 0.064 0.23 ± 0.065 Range 0.16–0.78 Range 0.16–0.41 Range 0.14–0.38 There were 6 routine studies (2 when patients with comorbidities were removed) and no transfusion studies with a TR velocity above 3.0 m/sec. There were 23 routine studies (18 when patients with comorbidities removed) and 6 transfusion studies with a TR velocity between 2.5 and 3.0 m/sec. The ratio of RV to systemic pressure was greater than one third in 11 routine patients (5 when patients with comorbidities were removed) and 1 transfusion patient. Conclusions PAHTN is present in a small number of children with SCD and may be exacerbated by other medical problems. Chronic transfusion may be protective against PAHTN. Prospective analysis of this population is warranted.

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Genomic Approaches to Identifying Risk for Pulmonary Artery Hypertension among Individuals with Sickle Cell Disease.

Blood ◽

10.1182/blood.v112.11.1442.1442 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1442-1442

Author(s):

Damian Silbermins ◽

Laura M. De Castro ◽

Jude C Jonassaint ◽

Shiaowen David Hsu ◽

Marilyn J. Telen ◽

...

Keyword(s):

Gene Expression ◽

Sickle Cell Disease ◽

Pulmonary Artery ◽

Sickle Cell ◽

Whole Blood ◽

Gene Signature ◽

Pulmonary Artery Hypertension ◽

Gene Set Enrichment Analysis ◽

Cell Disease ◽

Gene Signatures

Abstract Pulmonary artery hypertension (PAH) occurs in 30–50% of adult patients with sickle cell disease (SCD), with mortality ranging from 16 to 50% and a median survival of 25 months. Our objective was to use gene expression profiling to develop a gene signature predictor for PAH through the analysis of gene expression of blood cells from SCD patients with or without PAH. We hypothesized that these gene signatures could allow us to identify patients at risk for PAH, as well as to generate hypotheses as to the pathophysiology of PAH in SCD. We used Affymetrix U133A2 GeneChip to determine the RNA expression of both whole blood and leukocytes using PAXgene and Leukolock methods, respectively. The study population included patients homozygous for HbS or with HbSβ0 thalassemia. Subjects with PAH were ≥18 years old, in steady state, and had PAH either by 2D echo (TR jet ≥ 2.7 m/sec) or right-sided catheterization (mean PA pressure ≥ 30 mmHg). Patients were excluded if they were pregnant, had co-existing rheumatologic conditions or other inflammatory diseases, were on chronic transfusion therapy or had had a vaso-occlusive episode in the previous 4 weeks. The control subjects were patients with SCD but without PAH (TR jet ≤ 1.8 m/sec or mean PA pressure <25 mmHg). Hierarchical clustering based on the gene expression pattern from 7 patients with PAH and 6 controls showed a trend for the clustering of SCD patients with PAH away from SCD patients without PAH. This trend was present for the gene expression in both whole blood and leukocytes. A Bayesian regression analysis was then performed to identify a set of predictor gene signatures for the PAH phenotype (Figure 1) in SCD. Finally, using gene set enrichment analysis, we found that the leukocytes from patients with PAH were highly enriched in the gene sets deriving from hematopoietic stem cells, corroborating the hypothesis of hyperhemolysis and higher blood cell turnover in this population. Other pathways showing upregulation in PAH were PTEN, TGFβ, cyclin D1, WNT and PPAR. Although these data are preliminary, they suggest that PAH in SCD does indeed have a distinct gene signature profile that may become useful in identifying risk for PAH prospectively, as well as in directing further investigation into the pathogenesis of PAH in SCD. Figure Figure

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Concurrent Bilateral Central Retinal Artery Occlusion Secondary to Sickle Cell Crisis

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/23247096211028392 ◽

2021 ◽

Vol 9 ◽

pp. 232470962110283

Author(s):

Gowri Renganathan ◽

Piruthiviraj Natarajan ◽

Lela Ruck ◽

Roberto Prieto ◽

Bharat Ved Prakash ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Vision Loss ◽

Central Retinal Artery Occlusion ◽

Retinal Artery Occlusion ◽

Artery Occlusion ◽

Cell Disease ◽

Sickle Cell Crisis ◽

History Of ◽

Retinal Artery

Vascular occlusive crisis with a concurrent vision loss on both eyes is one of the most devastating disability for sickle cell disease patients. Reportedly occlusive crisis in the eyes is usually temporary whereas if not appropriately managed can result in permanent vision loss. A carefully managed sickle cell crisis could prevent multiple disabilities including blindness and stroke. We report a case of a 24-year-old female with a history of sickle cell disease who had acute bilateral vision loss during a sickle crisis and recovered significantly with a timely emergent erythrocytapheresis.

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