Hemorheological mechanisms for increased thrombosis in subjects using gestodene

Abstract

There are several possible mechanisms by which combined oral contraceptives (COC) use increase venous thromboembolism (VTE) risk. Melodene ® is a monophasic COC containing the third-generation progestin Gestodene (GSD), which is associated with increased risk of VTE.Therefore, the aim of this study was to investigate the possible alterations in viscoelastic parameters of whole blood and plasma clots along with the biophysical characteristics of erythrocytes and specifically fibrin fibers in females using a COC containing GSD. GSD appeared to have a significant impact on the biophysical characteristics of fibrin fiber networks. When GSD is combined with ethinylestradiol the viscoelastic properties of whole blood clots tend to become more prothrombotic. The alterations to and aggregation of erythrocytes accompanied with spontaneous formation of a fibrin "blanket" provides a possible mechanism for the increased occurrence of "red" clots, which can lead to occlusions in the vascular system. Thus, the increased risk of VTE associated with these COCs can be attributed to these erythrocyte-andfibrin-rich-clots occluding venous vessels. However, our findings also propose that these changes to the biophysical properties of both erythrocytes and fibrin, specifically spontaneous expansion of deformed fibrin networks, can also occlude vessels in the microcirculation, which could have lasting, subclinical complications for female users. We recommend that a thorough risk assessment, with specific focus on coagulation and other factors affecting fibrin formation, be done for each female before prescribing a GSD-containing COC. Females that "qualify" then need to be monitored on a regular basis to lower the risk of thrombotic events. K E Y W O R D S erythrocytes, fibrin, gestodene, hypercoagulability, viscoelasticity

The use of combined oral contraceptives and their relationship with venous thromboembolism

“…In this sense, the duration of contraceptive use as well as the generation of progesterone and the dose of estrogen in the COC have a clear influence on the risk of developing thrombosis. The risk of developing VTE is higher during the first 6 to 12 months after starting treatment, increasing from the fourth month of administration, but it is worth noting that the use of the third generation of progestins has a greater effect than the first (GIALERAKI et al, 2018;SWANEPOEL et al, 2018).…”

“…There are alterations and an aggregation of erythrocytes, mainly by the combined DRSP/20EE® and DRSP/30EE®, accompanied by the spontaneous formation of a fibrin network that causes the occurrence of clots, which leads to occlusions in the vascular system. Therefore, the increased risk of VTE associated with these COCs can be explained by these clots rich in erythrocytes and fibrin that occlude the venous vessels (SWANEPOEL et al, 2018;EMMERSON et al, 2018).…”

Drug Utilization Study on Oral Contraceptives provided from Social Security, Buenos Aires-Argentina: Risk and cost analysis according to the type of combination used

“…Indeed, progestins may counteract the procoagulant effects of estrogen to varying degrees. Many studies 4,15,16 indicated that progestogens with a high androgenic potency, antagonize the risk of VTE associated with EE more than newer progestins [6][7][8] . For this reason, contraceptives containing EE associated with "nor" compound (levonorgestrel, norgestrel or norgestimate) record a threefold increase in the risk for a VTE event 2,17 , which rises to a sixfold increase when the contraceptive contains desogestrel, gestodene, drospirenone, or cyproterone acetate 2,6,7 .…”