Background: Inhibition of sugammadex in coagulation tests have been reported but mechanisms are not revealed.

Aims: Establish the profile of inhibition of sugammadex.

Methods: We used a new in vitro pharmacodynamic plasma clot growth model (Thrombodynamics) and documented thrombin generation in this model. Lysis was studied with a plasma clot lysis method and in the Rotem. Sugammadex was evaluated in the range 0-600 µg/ml and spiked in normal plasma.

Results: Sugammadex did not have effects on growth rate of plasma clots, neither in normal nor in factor IX deficient plasma, and not on the size of clots formed after 30-60 minutes. Delay in starting was minor. In the thrombodynamics, thrombin generation in the layer close to immobilised tissue factor, but also further away in the clot, was significantly reduced, up to 50% for 600 µg/ml sugammadex.
The consequence suspected, was a reduced clot stabilisation by thrombomodulin-thrombin-TAFI. This was indeed documented in the plasma clot lysis test including thrombomodulin, but not in lysis without added thrombomodulin.
In the Rotem, there was a small increase in lag time, but no change in maximal clot firmness. Clot firmness is dependent upon participation of factor XIII related crosslinking, which was apparently not affected by sugammadex.
This profile of an anticoagulant is not reported before, preventing benchmarking with clinical effects of other coagulation inhibitors.

Conclusions: During treatment with sugammadex, clots will be formed normally, with a small delay in formation. Mainly clot quality is affected, which will persist after clearance of sugammadex. Fibrinolysis can be increased when thrombomodulin is present. This profile may be expected in vasculature with significant thrombomodulin such as the brain circulation.
Thus, sugammadex effects may increase bleeding risk via fibrinolysis in tissues with high fibrinolytic status and with expression of thrombomodulin, such as in the brain. This suggests rational intervention and targeting with fibrinolysis inhibitors.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/profile-of-effect-of-sugammadex-on-coagulation-and-fibrinolysis/