Corticosteroids and increased risk of readmission after acute chest syndrome in children with sickle cell disease

Strouse, John J.; Takemoto, Clifford M.; Keefer, Jeffrey R.; Kato, Gregory J.; Casella, James F.

doi:10.1002/pbc.21336

Cited by 103 publications

(76 citation statements)

References 24 publications

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“…Glucocorticoids attenuate the severity of sickle-cell vaso-occlusive pain crisis, the acute chest syndrome, and the hyperhemolysis syndrome. It will be interesting to investigate in clinical studies whether enhanced Hp synthesis in these patients is among the mechanisms involved in the protective glucocorticoid effect (58)(59)(60)(61). Additionally, our data demonstrate that the Hb-Hp complex retains oxygen-binding characteristics with prolonged circulating time.…”

Section: Discussionmentioning

confidence: 97%

Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs

Boretti¹,

Buehler²,

D’Agnillo³

et al. 2009

J. Clin. Invest.

125

175

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Release of hemoglobin (Hb) into the circulation is a central pathophysiologic event that contributes to morbidity and mortality in chronic hemolytic anemias and severe malaria. These toxicities arise from Hb-mediated vasoactivity, possibly due to NO scavenging and localized tissue oxidative processes. Currently, there is no established treatment that targets circulating extracellular Hb. Here, we assessed the role of haptoglobin (Hp), the primary scavenger of Hb in the circulation, in limiting the toxicity of cell-free Hb infusion. Using a canine model, we found that glucocorticoid stimulation of endogenous Hp synthesis prevented Hb-induced hemodynamic responses. Furthermore, guinea pigs administered exogenous Hp displayed decreased Hbinduced hypertension and oxidative toxicity to extravascular environments, such as the proximal tubules of the kidney. The ability of Hp to both attenuate hypertensive responses during Hb exposure and prevent peroxidative toxicity in extravascular compartments was dependent on Hb-Hp complex formation, which likely acts through sequestration of Hb rather than modulation of its NO-and O 2 -binding characteristics. Our data therefore suggest that therapies involving supplementation of endogenous Hb scavengers may be able to treat complications of acute and chronic hemolysis, as well as counter the adverse effects associated with Hb-based oxygen therapeutics.

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Section: Discussionmentioning

confidence: 97%

Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs

Boretti¹,

Buehler²,

D’Agnillo³

et al. 2009

J. Clin. Invest.

125

175

View full text Add to dashboard Cite

show abstract

“…Could it be that the salutary effect of glucocorticoids in this setting is mediated partly by induction of Hp production, boosting its capacity to neutralize and clear vasculotoxic extracellular Hb? Sickle-cell vaso-occlusion sometimes can rebound in severity when the steroids are stopped or the dose is tapered (18)(19)(20). Could this be occurring because Hp levels then fall while hemolysis is still brisk, promoting once more the accumulation of plasma Hb and its consequent NO scavenging, oxidative toxicity, and acute vasculopathy?…”

Section: Figurementioning

confidence: 99%

Haptoglobin halts hemoglobin’s havoc

Kato¹

2009

J. Clin. Invest.

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“…Concerns over side effects, including avascular necrosis, rebound VOC (50), and association with hemorrhagic stroke (51,52), have limited enthusiasm regarding corticosteroid use in patients with SCD.…”

Section: Acs Treatmentmentioning

confidence: 99%

Pulmonary Complications of Sickle Cell Disease

Gladwin

Vichinsky²

2008

N Engl J Med

409

390

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Sickle cell disease (SCD) is a common monogenetic disorder with high associated morbidity and mortality. The pulmonary complications of SCD are of particular importance, as acute chest syndrome and pulmonary hypertension have the highest associated mortality rates within this population. This article reviews the pathophysiology, diagnosis, and treatment of clinically significant pulmonary manifestations of SCD, including acute chest syndrome, asthma, and pulmonary hypertension in adult and pediatric patients. Clinicians should be vigilant in screening and treating such comorbidities to improve patient outcomes.

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Corticosteroids and increased risk of readmission after acute chest syndrome in children with sickle cell disease

Cited by 103 publications

References 24 publications

Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs

Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs

Haptoglobin halts hemoglobin’s havoc

Pulmonary Complications of Sickle Cell Disease

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