TY - JOUR
T1 - New insights into the pathophysiology and development of novel therapies for sickle cell disease
AU - Moerdler, Scott
AU - Manwani, Deepa
N1 - Publisher Copyright:
© 2018 American Society of Hematology. All rights reserved.
PY - 2018/11/30
Y1 - 2018/11/30
N2 - Although the seminal event in sickle cell disease is the polymerization of abnormal hemoglobin, the downstream pathophysiology of vasoocclusion results fromheterotypic interactions between the altered, adhesive sickle cell red blood cells, neutrophils, endothelium, and platelets. Ischemia reperfusion injury, hemolysis, and oxidant damage all contribute to heightened inflammation and activation of the hemostatic system. These various pathways are the focus of emerging treatments with potential to ameliorate disease manifestations. This review summarizes the considerable progress in development of these agents despite challenges in selection of study end points and complex pathophysiology.
AB - Although the seminal event in sickle cell disease is the polymerization of abnormal hemoglobin, the downstream pathophysiology of vasoocclusion results fromheterotypic interactions between the altered, adhesive sickle cell red blood cells, neutrophils, endothelium, and platelets. Ischemia reperfusion injury, hemolysis, and oxidant damage all contribute to heightened inflammation and activation of the hemostatic system. These various pathways are the focus of emerging treatments with potential to ameliorate disease manifestations. This review summarizes the considerable progress in development of these agents despite challenges in selection of study end points and complex pathophysiology.
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U2 - 10.1182/asheducation-2018.1.493
DO - 10.1182/asheducation-2018.1.493
M3 - Review article
C2 - 30504350
AN - SCOPUS:85058748459
SN - 1520-4391
VL - 2018
SP - 493
EP - 506
JO - Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program
JF - Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program
IS - 1
ER -