Challenges in anticoagulation management COVID-19 associated thrombosis and factor xa inhibitor therapy

Anticoagulants are widely used to prevent and treat blood clots. In recent years, direct oral anticoagulants (DOACs) have largely replaced traditional vitamin K antagonists because they are easier to use and have a more favourable safety profile. As the number of patients receiving anticoagulants continues to grow, new clinical challenges emerge regarding their safe and effective use.
This thesis addresses several of these challenges. The first part focuses on thrombosis in patients with COVID-19. Early in the pandemic, we demonstrated that hospitalised COVID-19 patients, particularly those admitted to the intensive care unit, had a high risk of venous thromboembolism despite standard thromboprophylaxis. We subsequently investigated the mechanism underlying this increased risk using vessel-on-chip technology, showing that plasma from severely ill COVID-19 patients can induce endothelial activation and microthrombosis. In addition, we evaluated anticoagulation strategies in COVID-19 patients and studied whether pre-existing antithrombotic therapy could improve clinical outcomes.
The second part focuses on direct factor Xa inhibitors, a commonly prescribed group of DOACs. We reviewed and evaluated strategies to reverse their anticoagulant effects in patients with major bleeding, including the use of andexanet alfa. Furthermore, we investigated the absorption and safety of DOACs in patient populations that are often underrepresented in clinical trials, such as patients with intestinal failure and patients who have undergone bariatric surgery.
Together, the findings of this thesis contribute to improve the understanding of anticoagulation management in complex clinical settings and support more personalized treatment decisions for patients at risk of thrombosis or bleeding.