Effect of intravitreal injection of aflibercept on blood coagulation parameters in patients with age-related macular degeneration

Abstract

Purpose: Treatment with intravitreal injections of anti-vascular endothelial growth factor agents has been associated with an increased risk of arterial thromboembolic events. The aim of the present pilot study was to assess the effect of a single intravitreal injection of aflibercept on coagulation. Methods: Treatment-naïve patients with age-related macular degeneration (n = 47), who were scheduled to undergo treatment with intravitreal injections of aflibercept, were enrolled. None of the included patients received any anticoagulation therapy or had a history of a recent arterial thromboembolic event. Blood samples were collected before the first intravitreal injection, and at 7 and 30 days after aflibercept administration. We evaluated coagulation parameters, such as platelet count and plasma fibrinogen and D-dimer levels; functional clotting parameters, such as prothrombin time, international normalized ratio, and activated partial thromboplastin time; and anticoagulant parameters, such as the levels of Proteins S and C. Results: The levels of all of the evaluated biomarkers were within the normal range at baseline and at both the time points throughout the study. No statistically significant changes were observed in any of the measured parameters at 1 week and 1 month after aflibercept administration. Conclusion: A single intravitreal injection of aflibercept in treatment-naïve patients with exudative age-related macular degeneration has no statistically significant effect on blood coagulation parameters for up to 1 month after aflibercept administration. Our results also provide an explorative statistical data, and further studies are required to evaluate any significant clinical effects of aflibercept on blood coagulation parameters. ClinicalTrials.gov ID: NCT03509623.

Evaluation of Blood Coagulation Parameters and ADMA, NO, IL-6, and IL-18 Serum Levels in Patients with Neovascular AMD before, during, and after the Initial Loading Phase of Intravitreal Aflibercept

“…To date, four studies assessing the influence of intravitreal injections of anti-VEGF agents on the coagulation parameters have been published [ 9 , 13 , 20 , 21 ]. In patients with proliferative diabetic retinopathy (PDR), the effect of IVB on prothrombin time was evaluated [ 13 ], while another study evaluated clotting time, serum fibrinogen level, and blood viscosity in patients with CNV treated with IVR [ 9 ].…”

“…In the third study, changes in APTT and PT were measured in patients with nAMD who received IVA [ 20 ]. Georgakopoulos et al assessed the effect of IVA on platelet count, PT, APTT, and fibrinogen, D-dimer, and protein C and S levels in the serum of patients with AMD [ 21 ]. Altinkaynak et al revealed a decrease in APTT and PT values both one month after the first IVA injection and one month after the second injection in patients with nAMD; however, in both measurement points the results were not statistically significant [ 20 ].…”

“…The results showed a reduction in prothrombin time in the PDR group within 2 weeks after IVB injection; however, the prothrombin time didnot exceed the normal limit in any of the measurements [ 13 ]. Georgakopoulos et al showed no statistically significant changes in the value of any of the parameters tested, one week after and one month after IVA administration [ 21 ]. Similarly, our results showed no significant changes in PT or APTT in patients following IVA.…”

“…It can be assumed that the prolongation of TT may result from a decrease in serum fibrinogen (hypofibrinogenemia) or its structural abnormalities resulting in an abnormal function (dysfibrinogenemia) [ 15 ]. Georgakopoulos et al revealed no significant changes in serum fibrinogen concentration at 7 and 30 days after a single IVA injection, and, thus, the influence of IVA on fibrinogen function should be considered [ 21 ]. Fibrinogen is a glycoprotein synthesized in the liver consisting of three heterodimers (αA, βB, γ) connected by disulfide bridges and has the ability to bind to the GPIIb/IIIa receptor located on the surface of platelets and megakaryocytes [ 26 ].…”

Changes of plasma nitric oxide, endothelin-1, and blood coagulation following intravitreal conbercept

“…We hypothesize that the causes may be multifaceted including specific drug related blood chemistry changes and patients’ health conditions. A few studies have looked into the blood coagulation parameters following intravitreal injection of bevacizumab 14 or aflibercept 9 , 10 or ranibizumab 12 . In contrast, so far there is no similar report following intravitreal conbercept.…”