Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Dec;93(12):1439-1443.
doi: 10.1002/ajh.25289. Epub 2018 Oct 23.

The missing middle of sickle therapeutics: Multi-agent therapy, targeting risk, using biomarkers

Robert P Hebbel  1 , Jacques Elion  2 , Abdullah Kutlar  3
Affiliations

The missing middle of sickle therapeutics: Multi-agent therapy, targeting risk, using biomarkers

Robert P Hebbel et al. Am J Hematol. 2018 Dec.
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
The vicious cycle of SCA, with ischemia/reperfusion pathophysiology as the driver of incessant, systemic inflammation
Figure 2
Figure 2
Taming the instability of “steady state.” (A) Instability of steady state is shown by biomarkers sampled longitudinally from three historically mild SCA subjects, without current symptoms, and no acute events >3 months before or after this study. Each symbol type indicates one of the subjects. For each biomarker, the shaded area indicates range for normal subjects. (B) Testing for efficacy while controlling for instability. Here, efficacy of oral sulfasalazine for downregulating endothelial adhesion molecule expression in one SCA subject was tested. Activation is expressed as % of circulating endothelial cells (CEC) positive for three adhesion molecules (open symbols) and tissue factor (closed symbol). Steady state baseline is established empirically by all values collected off‐drug (the box). Dark bars show days on‐drug; the indicated day numbers identify the start and stop dates for the mini‐trials. Figure reproduced with permission from Ref. 13
See this image and copyright information in PMC

References

    1. Piel FB, Hay S, Gupta S, Weatherall DJ, Williams TN. Global burden of sickle cell anaemia in children under five, 2010‐2050: modelling based on demographics, excess mortality, and interventions. PLoS Med. 2013;10(7):e1001484. - PMC - PubMed
    1. Mozzarelli A, Hofrichter J. EatonWA. Delaytime of hemoglobin S polymerization prevents most cells from sickling in vivo. Science. 1987;237(4814):500‐506. - PubMed
    1. Ferrone FA. Polymerization and sickle cell disease: a molecular view. Microcirculation. 2004;11(2):115‐128. - PubMed
    1. Hebbel RP. Adhesive interactions of sickle erythrocytes with endothelium. J Clin Invest. 1997;100(11 Suppl):S83‐S86. - PubMed
    1. Kaul DK, Fabry ME, Nagel RL. Microvascular sites and characteristics of sickle cell adhesion to vascular endothelium in shear flow conditions: pathophysiological implications. Proc Natl Acad Sci USA. 1989;86(9):3356‐3360. - PMC - PubMed