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Thrombocytopenia is associated with severe retinopathy of prematurity

Journal article
Authors B. Cakir
R. Liegl
Gunnel Hellgren
Pia Lundgren
Y. Sun
S. Klevebro
Chatarina Löfqvist
Clara Mannheimer
S. Cho
A. Poblete
R. Duran
B. Hallberg
J. Canas
V. Lorenz
Z. J. Liu
M. C. Sola-Visner
L. E. H. Smith
Ann Hellström
Published in Jci Insight
Volume 3
Issue 19
ISSN 2379-3708
Publication year 2018
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience
Language en
Links dx.doi.org/10.1172/jci.insight.9944...
Keywords platelet alpha-granules, oxygen-induced retinopathy, pathological, angiogenesis, endothelial-cells, p-selectin, expression, proteins, release, mouse, transfusions
Subject categories Clinical Medicine

Abstract

Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in response to vessel loss. Platelets regulate angiogenesis and may influence ROP progression. In preterm infants, we assessed ROP and correlated with longitudinal postnatal platelet counts (n = 202). Any episode of thrombocytopenia (< 100 x 10(9)/l) at >= 30 weeks postmenstrual age (at onset of ROP) was independently associated with severe ROP, requiring treatment. Infants with severe ROP also had a lower weekly median platelet count compared with infants with less severe ROP. In a mouse oxygen-induced retinopathy model of ROP, platelet counts were lower at P17 (peak neovascularization) versus controls. Platelet transfusions at P15 and P16 suppressed neovascularization, and platelet depletion increased neovascularization. Platelet transfusion decreased retinal of vascular endothelial growth factor A (VEGFA) mRNA and protein expression; platelet depletion increased retinal VEGFA mRNA and protein expression. Resting platelets with intact granules reduced neovascularization, while thrombin-activated degranulated platelets did not. These data suggest that platelet releasate has a local antiangiogenic effect on endothelial cells to exert a downstream suppression of VEGFA in neural retina. Low platelet counts during the neovascularization phase in ROP is significantly associated with the development of severe ROP in preterm infants. In a murine model of retinopathy, platelet transfusion during the period of neovascularization suppressed retinopathy.

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