The role of inflammation and leukocytes in the pathogenesis of sickle cell disease

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Acute and chronic vascular occlusion underlies much of the morbidity and mortality in sickle disease. Abnormal polymerization of deoxygenated hemoglobin S (HbS) resulting in stiff, non-deformable erythrocytes is central to sickle cell pathogenesis. However, a complex interplay of many factors determines the balance between adequate blood flow and vessel obstruction. Serum markers of inflammation have provided evidence for a state of chronic inflammation in sickle cell disease (SCD). Inflammation promotes endothelial adherence to sickle erythrocytes. Studies demonstrating a beneficial effect of steroid therapy for painful episodes and acute chest syndrome provide indirect evidence for the role of inflammation in this disease. Leukocytosis, in the absence of infection, is common in SCD patients and predicts for stroke, acute chest syndrome, and overall mortality. Neutrophils and monocytes have been shown to be activated in these patients. Activated leukocytes further promote vascular inflammation and vessel damage. A reduction in leukocytes, and thus inflammation, may partially explain the beneficial effects of hydroxyurea in this disease. These data provide a strong rationale for clinical studies of therapy directed at inflammation and/or leukocytes in sickle cell disease.

Original languageEnglish (US)
Pages (from-to)403-412
Number of pages10
JournalHematology
Volume5
Issue number5
StatePublished - 2001

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Sickle Cell Anemia
Leukocytes
Inflammation
Acute Chest Syndrome
Blood Vessels
Erythrocytes
Sickle Hemoglobin
Hydroxyurea
Mortality
Leukocytosis
Polymerization
Monocytes
Neutrophils
Biomarkers
Stroke
Steroids
Morbidity
Therapeutics
Infection

Keywords

  • Inflammation
  • Monocytes
  • Neutrophils
  • Sickle cell
  • Vascular disease

ASJC Scopus subject areas

  • Hematology

Cite this

The role of inflammation and leukocytes in the pathogenesis of sickle cell disease. / Wun, Theodore.

In: Hematology, Vol. 5, No. 5, 2001, p. 403-412.

Research output: Contribution to journalArticle

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