Background: The use of combined oral contraceptives has been associated with an increased risk of thromboembolic disease. Current in vitro tests are focusing on one or some sets of multiple factors but are not really pharmacodynamic tests. In this study  we present thrombodynamics, which is an elegant in vitro analysis that resembles in vivo coagulation starting from a prothrombotic surface and  gives insight in the spatial dynamics of the formation of a fibrin clot and thrombin generation.

Aims: Investigate the effect of 6 month treatment of three different types combined oral contraceptives belonging to either the 2^nd generation or a 3rd generation COC (Ethinylestradiol 30 µg – Desogestrel 150 µg; or Ethinylestradiol 20 µg – Desogestrel 150 µg) in healthy woman on fibrin clot growth  and thrombin generation.

Methods: The coagulation state of blood plasma samples was quantitatively evaluated using a Thrombodynamics Analyzer System T-2 (Hemacore). This system records the fibrin clot light scattering changes in a time-lapse video microscopy mode and  records the fluorescence signal during cleavage of synthetic AMC-based substrate by thrombin. Next, numerical parameters are calculated describing the coagulation process.

Results: Data show that fibrin clot formation and thrombin generation are  increased after 6 months treatment of combined oral contraceptives. Figure 1 shows the size of the clot before and after 6 month treatment; Figure 2 shows the individual changes in thrombin formation in the clot.

Example of images of fibrin clot formed from inmmobilized tissue-factor into thin layer of plasma sample before (left) and after (right) 6 months 2nd (A) or 3rd generation (B) COC treatment.Figure 1

The stationary amplitude of thrombin within the clot before and after 6 months COC treatment of 10 subjects.Figure 2

Conclusions: The use of three types of COC (30EELNG, 30EEDSG and 20EEDSG) is involved in the increased risk of thromboembolic disease. Both the fibrin clot size and thrombin generation increased after 6 months treatment of COC. The read outs are consequences of multiple factors unlike reductionistic approaches of other tests. Furthermore, with thrombodynamics the ‘high hemostatic responders’ can be identified who may have the highest risk to develop thrombogenic effects while using COCs.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/a-new-pharmacodynamic-test-to-evaluate-effects-of-oral-contraceptives-on-coagulation/