Thrombocytopenia is associated with severe retinopathy of prematurity
Bertan Cakir, … , Lois E.H. Smith, Ann Hellström
Bertan Cakir, … , Lois E.H. Smith, Ann Hellström
Published October 4, 2018
Citation Information: JCI Insight. 2018;3(19):e99448. https://doi.org/10.1172/jci.insight.99448.
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Research Article Angiogenesis Vascular biology

Thrombocytopenia is associated with severe retinopathy of prematurity

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 × 109/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.

Authors

Bertan Cakir, Raffael Liegl, Gunnel Hellgren, Pia Lundgren, Ye Sun, Susanna Klevebro, Chatarina Löfqvist, Clara Mannheimer, Steve Cho, Alexander Poblete, Rubi Duran, Boubou Hallberg, Jorge Canas, Viola Lorenz, Zhi-Jian Liu, Martha C. Sola-Visner, Lois E.H. Smith, Ann Hellström

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Figure 1

Platelet count and severity of retinopathy of prematurity.

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Platelet count and severity of retinopathy of prematurity. (A) Platelet ...
(A) Platelet counts of all infants screened for retinopathy of prematurity (ROP) per postmenstrual age week (PMA) (each dot represents the mean weekly platelet count of each individual; the black solid line represents the mean platelet count of all individuals) (n = 202). (B) Mean PMA platelet count (1 × 109/l) of all infants with severe ROP requiring laser treatment (n = 49; solid line) and with no or less severe ROP not requiring laser treatment (n = 153; dashed line). Mean weekly platelet counts per infant were lower in infants treated for severe ROP compared with infants with no or less severe disease, at almost all postnatal weeks. The difference in mean weekly platelet counts further increased at ≥30 weeks PMA in the proliferative ROP phase. All treated infants with any thrombocytopenia at ≥30 weeks PMA also had some thrombocytopenia in the initial vessel-loss phase of ROP (<30 weeks PMA). *P < 0.05, **P < 0.01, ***P < 0.001. Error bars represent 95% CI. Mann-Whitney U test was used for statistical analysis.