POSSIBILITIES OF INHIBITING ANTICOAGULANT ACTIVITIES THAT INHIBIT XA-FACTOR

The article deals with the possibility of suppressing the effect of drugs inhibiting the activity of the Xa-Factor of the clotting blood system. Wide indications for oral anticoagulants are atrial fibrillation, venous thrombosis, thromboembolism, etc. - more and more patients are involved in this treatment, and the use of nonvitamin-K-associated (NOAC) anticoagulants is increasing. Although these drugs have a relatively good safety profile, their use may also lead to “large”, including life-threatening, bleeding. Current approaches to the treatment of such bleeding include, in addition to a wide range of non-specific hemostatic measures, the use of drugs that can selectively suppress the effects of NOAC. A specific antagonist, the andexanet-alfa, has been developed relatively recently for anticoagulants that suppress the activity of the coagulation Xa-factor (such as Apixaban and Rivaroxaban). This drug represents a molecule of catalytically inactive modified human recombinant Xa-factor, obtained from human Xa-factor by genetically engineered modification. Being inactive with respect to coagulation, the drug molecule has the ability to bind the molecules of Xa-factor inhibitors with a high degree of strength, neutralizing their action.In the recently completed ANNEXA-4 clinical trial, 352 patients (average age 77 years) were injected with Rivaroxaban (36%), Apixaban (55%), Edoxaban (3%) or Enoxaparin (6%), with life-threatening bleeding (intracranial - 64%, gastrointestinal - 26%). The study showed that the anti-Ha activity of NOAC decreased by more than 90% in the first minutes after the introduction of andexanet and remained reduced 12 hours after its infusion. In 82% of patients in the ANNEXA-4 study, the hemostatic effect of the andexanet was assessed as excellent or good, and it did not differ significantly depending on the sex, age of the patients, the dose of the andexanet and the place of bleeding. No significant procoagulant or immunogenic effect of the andexanet was found. Thus, in the case of life-threatening bleeding with Xa-factor inhibitory anticoagulants, the use of their specific andexanet-alfa antagonist is recommended by clinical guidelines and should be an integral part of the hemostatic therapy and may potentially extend the safety spectrum of these anticoagulants.