Angiopoietin-2 as a Marker of Retinopathy in Children and Adolescents With Sickle Cell Disease: Relation to Subclinical Atherosclerosis

Abstract

Objectives: Angiopoietin-2 (Ang-2) is a multifaceted cytokine that functions in both angiogenesis and inflammation. A proangiogenic state has been found in adults with sickle cell disease (SCD), mainly because of elevated Ang-2 levels. We determined Ang-2 level in 40 children and adolescents with SCD compared with 40 healthy controls and assessed its relation to retinopathy as well as carotid intimamedia thickness (CIMT). Methods: Hematologic profile, serum ferritin, and serum Ang-2 were measured. CIMT was assessed using high-resolution ultrasound. Fundus examination was performed followed by fundus fluorescein angiography. Optical coherence tomography angiography (OCTA) was used to find small vascular changes not clinically manifested. Results: Ang-2 levels and CIMT were significantly higher in SCD patients compared with controls. The incidence of nonproliferative retinopathy was 45%. SCD patients with retinopathy were older in age with a history of sickling crisis of >3 attacks per year and had a higher incidence of sickle cell anemia than sickle β-thalassemia. Ang-2 cutoff value 9000 pg/mL could significantly detect the presence of retinopathy among SCD patients with 100% sensitivity and specificity. Serum Ang-2 levels were positively correlated with HbS and CIMT. Logistic regression analysis revealed that Ang-2 and HbS significantly contribute to retinopathy among patients with SCD. Conclusions: Elevated Ang-2 highlights the role of angiogenesis in the pathophysiology of SCD and may be considered a promising marker for screening of patients at risk of sickle retinopathy and vascular dysfunction.

Atypical Retro Internal Limiting Membrane Haemorrhage in Homozygous Sickle Cell Disease

“…cavity containing yellow hemosiderin-laden macrophages, which was compatible with our clinical presentation, usually resulting from a resorbed salmon patch haemorrhage [5]. In this case, it would have been interesting to measure the angiopoietin-2, recently known to be a proangiogenic cytokine blood marker that becomes elevated in acute SCR in children and adolescent, and to follow her blood kinetic during the haemorrhage resorption, helping us to date it more accurately [6].…”

Decreased parasite burden and altered host response in children with sickle cell anemia and severe anemia with malaria

“…Specific factors associated with severe disease and mortality in severe malaria, including the proinflammatory cytokine tumor necrosis factor a (TNF-a) and components of the angiopoietin (Angpt)-Tie-2 system, are also associated with clinical severity in SCA. [17][18][19][20][21][22][23] However, there have been no studies to date comparing these and other host responses in children with HbSS vs HbAA during episodes of severe anemia with Plasmodium falciparum parasitemia, or how the host response may alter parasite sequestration and density. In the present study, we assessed differences in children with HbSS vs HbAA in parasite biomass and markers of inflammation and endothelial activation during severe anemia with P falciparum parasitemia to better determine how SCA affects the host response to P falciparum during severe malaria.…”

“…1,19,23,[29][30][31][32][33] Recent data have implicated the Angpt-Tie-2 system in the pathogenesis of SCA and severe malaria, where elevated Angpt-2 and decreased Angpt-1 correlate with disease severity. [17][18][19][20][21][22] We quantitated levels of these and other biomarkers of endothelial activation as well as angiogenic cytokines vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) in this study population (Table 2). Median Angpt-2 was threefold higher in the children with HbSS compared with HbAA (5.0 vs 1.7 ng/mL; P 5 .01; Table 2).…”

Multiple inducers of endothelial NOS (eNOS) dysfunction in sickle cell disease

“…A general discussion of all endothelial‐derived vasoregulatory molecules is beyond the scope of this eNOS‐focused review. However, we do note that SCD subjects are reported to have elevated levels of the vasoconstrictors endothelin‐1 (ET‐1), 104 angiopoietin‐2 (Ang‐2) 105 and thromboxane A2. Also reported is a depressed level of the vasodilator prostacyclin, although platelet activating factor and prostaglandin E2 levels are reportedly elevated.…”