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FACTOR XI, THE TARGET OF NEW CLASSES OF ANTICOAGULANTS – REALITY AND PERSPECTIVES

ANA-MARIA VLĂDĂREANU 1, ADRIAN ROȘCA 2*, ILEANA RALUCA NISTOR 3

1 “Carol Davila” University of Medicine and Pharmacy, Department of Haematology, Emergency University Hospital of Bucharest, Romania 169 Splaiul Independentei, 050098 Bucharest, Romania
2 “Carol Davila” University of Medicine and Pharmacy, Department of Functional Sciences, Division of Physiology, Bucharest, 8 Eroii Sanitari Ave., 050470 Bucharest, Romania
3 “Carol Davila” University of Medicine and Pharmacy, Department of Neurology, Emergency University Hospital of Bucharest, 169 Splaiul Independentei, 050098 Bucharest, Romania

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Factor XI is an important element in the classical intrinsic coagulation pathway and has a nuanced role in cellular coagulation. Its involvement in thrombogenesis is major, while it plays a minor role in haemostasis. Clinical trials in Haemophilia C have shown reduced venous/arterial thrombotic events and minimal to moderate bleeding. These data have led to the development of pharmacological FXI inhibitors, which either reduce the synthesis or the activity of FXI. Unlike classical anticoagulants - heparins, vitamin K antagonists, new direct oral anticoagulants - FXI inhibitors have the effect of decoupling haemostasis from thrombosis, thereby presenting a lower risk of bleeding. Multiple Phase II clinical studies using FXI inhibitors have shown antithrombotic (anticoagulant) efficacy similar to classical anticoagulants, but with a lower risk of bleeding. Overall, results are somewhat different in preventing stroke in atrial fibrillation, venous thromboembolism in orthopaedic interventions or cancer, and complications of end-stage renal disease with haemodialysis. There are several ongoing phase II and III clinical trials investigating the role of FXI inhibitors. These drugs are not thought to replace treatment with classical anticoagulants, but they appear to be an alternative in several specific pathological situations.