Coagulation after transcatheter aortic valve replacement: Still a black box?

Pioneering roots of transcatheter aortic valve replacement (TAVR) date back to the early 1990s when Andersen and colleagues first presented their prototype of a transcatheter valve. Cribier achieved a clinical breakthrough by implanting a transcatheter aortic valve in a critically ill patient in 2002. Since then, TAVR has become a routine therapy for elderly patients with acquired aortic valve stenosis. For this procedure, sufficient periprocedural anticoagulation is mandatory. The implantation of potentially thrombogenic material into the cardiovascular system harbors the risk of thrombotic events, including stroke or bioprosthetic valve thrombosis, to name just a few.¹ Despite significant technical advances since the introduction of transfemoral TAVR, vascular bleeding complications still occur.² Finding the right balance between thrombosis and bleeding after the procedure is equally important. Thrombin, antithrombin, fibrinogen, and platelets play a vital role in the coagulation cascade. The course of these factors is essential to understand changes in coagulation after TAVR.

In the current issue of this journal, Katayama and colleagues have addressed this topic in a prospective single-center observational study.³ Almost half of the initial 539 patients were excluded to finally analyze a clean patient cohort, and the most frequent valve types (balloon-expandable and self-expandable) were used. Thrombin-antithrombin complex (TAT) and Fibrin degradation products (FDP) were used as surrogate parameters for changes in the coagulation system.

TAT is a coagulation marker and is evidence of increased thrombin formation or thrombosis. Conversely, FDP is a marker for fibrinolysis. Finally, the drop of platelets was observed over time.

Interestingly, a dynamic shift of coagulation status, such as a marked increase of the TAT, was observed in the very early phase after TAVR (first hour). Simultaneously—and with a high correlation to the TAT peak—a significant drop of platelets was seen. It is well known that platelet drop occurs after TAVI⁴; however, the mechanism is not clearly understood. Especially the higher TAT levels and more significant platelet drop in patients with balloon-expandable transcatheter valves require further investigation. In contrast to the dynamic changes of TAT, FDP levels increased more gradually and consistently in both valve types.

This study has provided insights into the coagulation system and platelets after TAVR; nevertheless, open questions remain. The authors hypothesize that the drop in platelet count may be due to mechanical destruction, overconsumption, or rapid shear stress. However, other studies have additionally shown a significant drop in hemoglobin levels during and in the early period after the procedure.⁴ However, this drop may also be caused by bleeding or hemodilution, as a significant amount of hyperosmolar contrast medium is used during the procedure. The role of this contrast medium and infusion fluid in the drop of platelets and hemoglobin has not been investigated to date.

The significance of protamine on the formation of TAT in TAVR patients needs to be clarified. Experimental studies have shown a reduction in thrombin generation by administering higher doses of protamine. Protamine markedly reduced tissue factor-initiated thrombin generation in human plasma. A recent randomized trial from Australia has proven the effect of protamine in terms of an increased rate of hemostasis effect and a decreased time to hemostasis.⁵ The effect of protamine in different dosages on the postoperative course of thrombin generation in TAVR patients is unclear.

Coagulation after transcatheter aortic valve replacement—still a black box in 2024? Maybe yes, but the good work from Katayama and colleagues has thrown light into this black box, and now it is a dark gray. More research in this field is necessary.

The authors declare no conflict of interest.