Thrombin-activated inhibitor of fibrinolysis and efficacy and safety of long-term warfarin treatment in patients with venous thromboembolic complications


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Aim. To study effects of thrombin-activated fibrinolysis inhibitor (TAFI) on efficacy and safety of long-term anti-coagulant treatment in patients with venous thromboembolic complications (VTEC). Material and methods. A total of 111 patients with a history of an episode of deep vein thrombosis (DVT) and/or pulmonary artery thromboembolism (PATE) entered the study. All the patients received unfractionated or low-molecular heparin for at least 5 days than switch on warfarin (target values of INR 2,0-3,0). Baseline blood levels of TAFI were measured. The patients were followed up for 18 months. Recurrent (DVT/TAFI and hemorrhagic complications (HC) were end points. Also, frequency of complete lysis of deep vein thrombi was assessed after 12 months of treatment.
Results. A TAFI level varied from 50 to 217% (median 106%, interquartile rage 90-133%). TAFI concentration positively correlated with fibrinogen and thromb size. The patients were divided into two groups depending on TAFI content: group 1 patients had low TAFI (under 25th percentile; < 90%); patients of group 2 had high TAFI (above 25th percentile; > 90%). Group 1 patients were characterized by less stable anticoagulation. This association did not depend on genetic characteristics which determine sensitivity to warfarin (CYP2C9 and VKORC1). Low TAFI was associated with reduced risk of DVT for 18 months and higher probability of complete lysis of the thrombi after 12 months of anticoagulant therapy compared to VTEC patients with high TAFI. No differences were found by TAFI level in patients with HC and without HC, but in HC patients low TAFI was associated with spontaneous hemorrhages and bleeding in therapeutic INR values.
Conclusion. The results of this pilot study evidence that a TAFI level can be one of the factors influencing efficacy and safety of long-term anticoagulant therapy in patients with VTEC on warfarin treatment.

About the authors

Natal'ya Mikhaylovna Vorob'eva

Email: natalyavorobjeva@mail.ru

Elizaveta Pavlovna Panchenko

Email: lizapanchenko@mail.ru

Anatoliy Borisovich Dobrovol'skiy

Email: abdobrovolsky@inbox.ru

Elena Vladimirovna Titaeva

Email: evlti@mail.ru

O V Ermolina

T V Balakhonova

Zukhra Bilyalovna Khasanova

Email: khasanova@mail.ru

Anton Yuvenal'evich Postnov

Email: anton-5@mail.ru

Aleksandr Ivanovich Kirienko

Email: phlebo-union@mtu-net.ru

N M Vorobyeva

Russian Research Cardiology Center, Moscow

Russian Research Cardiology Center, Moscow

E P Panchenko

Russian Research Cardiology Center, Moscow

Russian Research Cardiology Center, Moscow

A B Dobrovolsky

Russian Research Cardiology Center, Moscow

Russian Research Cardiology Center, Moscow

E V Titaeva

Russian Research Cardiology Center, Moscow

Russian Research Cardiology Center, Moscow

O V Ermolina

Russian Research Cardiology Center, Moscow

Russian Research Cardiology Center, Moscow

T V Balakhonova

Russian Research Cardiology Center, Moscow

Russian Research Cardiology Center, Moscow

Z B Khasanova

Russian Research Cardiology Center, Moscow

Russian Research Cardiology Center, Moscow

A Yu Postnov

Russian Research Cardiology Center, Moscow

Russian Research Cardiology Center, Moscow

A I Kirienko

N. I. Pirogov Russian State Moscow University, Moscow

N. I. Pirogov Russian State Moscow University, Moscow

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