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

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 anticoagulantsheparins, 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. RezumatFactorul XI este un element important al cii clasice intrinseci a coagulrii si are un rol nuanat n coagularea celular.Implicarea sa n trombogenez este major, n timp ce n hemostaz prezint un rol minor.Studiile clinice investignd Hemofilia C au artat o reducere a evenimentelor trombotice venoase/arteriale i i prezena sngerrilor minime -moderate.Aceste date au condus la dezvoltarea unor inhibitori farmacologici ai FXI, care, fie reduc sinteza, fie activitatea FXI.Spre deosebire de anticoagulantele clasice -heparine, antagoniti ai vitaminei K, sau noile anticoagulante orale directe -inhibitorii FXI au un efect de decuplare a hemostazei de tromboz, prezentnd astfel un risc hemoragic mai mic.Mai multe studii clinice de faz II investignd inhibitorii FXI au evideniat o eficacitate antitrombotic (anticoagulant) similar cu cea a anticoagulantelor clasice, dar cu un risc mai sczut de sngerare.n general, rezultatele sunt oarecum diferite atunci cnd ne referim la prevenirea accidentului vascular cerebral n fibrilaia atrial, a trombembolismului venos n interveniile ortopedice sau in cancer i a complicaiilor bolii renale n stadiu terminal cu hemodializ.Sunt n desfurare mai multe studii clinice de faz II i III investignd rolul inhibitorilor FXI.Se crede c inhibitorii FXI(a) nu nlocuiesc tratamentul cu anticoagulantele clasice, dar par a reprezenta o alternativ n unele situaii patologice specifice.