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Ulrich Schraermeyer, Sigrid Schultheiss, Sabine Hofmeister, Sylvie Julien; Bevacizumab Immune Complexes Activate Platelets And Cause Thrombosis In Choroidal Vessels Of Primate Eyes. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5271.
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To examine the effect of intravitreal bevacizumab on primate eyes with particular focus on the influence of vascular endothelial growth factor (VEGF) inhibition by full length antibodies on thrombocyte activation in choroidal vessels. Recently it has been shown that bevacizumab can induce platelet aggregation, degranulation and thrombosis through complex formation with VEGF and activation of the platelet FccRIIa receptor and that this provides a better explanation for the thrombotic events observed in vivo 1.
Four Cynomolgus monkeys received an intravitreal injection of 1.25 mg bevacizumab. The eyes were enucleated and prepared for light (left eyes) and electron microscopy (right eyes) on days one, four, seven, and 14. Control eyes remained untreated. Bevacizumab was localized by immunocytochemistry. Thrombocytes and fibrin were stained by histochemistry.
At the light microscopic level, platelets occluding choriocapillaris or deeper choroidal vessels were observed locally in eyes of all 4 animals. Bevacizumab filled the total sectioned lumen of individual choroidal blood vessels, which is indicative for stasis. At the electron microscopic level, thrombocytes within the choriocapillaris exhibited typical signs of activation such as pseudopodia, vacuoles and degranulation. Electron dense granules resembling serotonin granules released from thrombocytes were present in the blood stream. Densely packed thrombocytes and leukocytes regionally occluded the choriocapillaris lumen of treated eyes completely. In the vicinity of such sites photoreceptors were also damaged, judged by the presence of isolated inner segments in the subretinal space. None of these described features was found in controls.
Intravitreal bevacizumab causes thrombi formation in the choriocapillaris and deeper choroidal vessels of primate eyes very likely mediated by the Fc receptor.References 1. Meyer T, Robles-Carrillo L, Robson T, Langer F, Desai H, Davila M, Amaya M, Francis JL, Amirkhosravi A. Bevacizumab immune complexes activate platelets and induce thrombosis in FCGR2A transgenic mice. J Thromb Haemost. 2009;7:171-181.
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