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.
View: Text | PDF
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

×

Figure 2

Platelet count in OIR and proof of concept.

Options: View larger image (or click on image) Download as PowerPoint
Platelet count in OIR and proof of concept. (A) Scheme of oxygen-induced...
(A) Scheme of oxygen-induced retinopathy (OIR): C57BL/6 mouse pups are exposed to 75% oxygen from P7–P12 to induce retinal vessel loss and are returned to room air at P12–P17. Below the scheme, 2 representative retinal whole-mount images, including magnification area, from normoxia and OIR P17 pups stained with lectin (see magnification below). P17 OIR pups have pathologic neovascularization compared with normoxia pups. (B) Platelet counts in mouse pups at P7, P12, and P17 with (red) (n = 10) or without (blue) (n = 6) OIR. Platelet count was reduced at P17 OIR (P = 0.0084). (C) Platelet counts were measured in whole blood after 0, 2, and 48 hours after anti-GPIbα antibody injection. A significant decrease in platelet count was seen at 2 and 48 hours after platelet depletion (P = 0.0029 and P < 0.0001). (D) Platelet transfusion proof of concept. WT neonatal mice were retro-orbitally transfused with 10 μl per gram of mouse of 5.0 × 106 platelets/μl. Total platelet counts were measured before transfusion (time 0), as well as 2 and 48 hours after transfusion. The platelet count increased by 42.3% after 2 hours (P = 0.0012). The initial increase was cleared by 58.6% after 48 hours but was still significantly increased compared with time 0 (P = 0.0093). Data represent mean ± SD. Two-tailed unpaired t test.