Recurrences of thromboses and hemorrhagic complications in patients with antiphospholipid syndrome during therapy with warfarin plus aspirin
- Authors: Kondrat'eva L.V.1, Patrusheva N.L.2, Patrushev L.I.2, Aleksandrova E.N.1, Kovalenko T.F.2, Ostryakova E.V.1, Reshetnyak T.M.1, Kondratyeva LV3, Patrusheva NL4, Patrushev LI4, Aleksandrova EN3, Kovalenko TF4, Ostryakova EV3, Reshetnyak TM3
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Affiliations:
- Научно-исследовательский институт ревматологии РАМН
- Институт биоорганической химии им. акад. М. М. Шемякина и акад. Ю. А. Овчинникова РАН
- Research Institute of Rheumatology, Russian Academy of Medical Sciences
- Acad. M. M. Shemyakin & Acad. Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
- Issue: Vol 82, No 5 (2010)
- Pages: 33-39
- Section: Editorial
- URL: https://journals.rcsi.science/0040-3660/article/view/30582
- ID: 30582
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Full Text
Abstract
Subjects and methods. Eighty-two patients diagnosed as having the antiphospholipid syndrome were examoned. Group 1 patients (n = 49) received warfarin alone as an antithrombotic drug; Group 2 patients (n = 33) had a combination therapy with warfarin plus aspirin. The efficiency of therapy was evaluated from the number and rate of recurrences of thromboses and transient ischemic attacks (TIA) and its safety was assessed from the frequency and number of hemorrhages during the study. The genetic variants of cytochrome P450 CYP2C9 were determined in 52 of the 82 patients; mutations in the gene for vitamin K epoxide reductase complex 1 (VCORC1) were revealed in 22 patients.
Results. During the follow-up, antithrombotic therapy was ineffective in 18.4 and 36.6% of the Groups 1 and 2 patients, respectively (p = 0.07). The rate of poor outcomes (thromboses and TIA) was 7 and 14.8 cases per 100 person-years, respectively. The first six months of warfarin therapy proved to be most risky for thrombotic events to occur - this period was responsible for 37% of bleedings. Hemorrhagic complications of antithrombotic therapy developed in 46.9 and 60.6% of Groups 1 and 2 patients, respectively (p = 0.26). Major hemorrhages were observed more frequently in the combination (warfarin plus low-dose aspirin) therapy group than in the warfarin monotherapy group. Mutant cytochrome P450 gene variants (CYP2C9*2 and CYP2C9*3) were present in 38.5% of the patients; VCORC1 gene mutations were observed in 27.3%. The number of nasal and gingival hemorrhages was increased in patients with CYP2C9*3 and homozygous VCORC1 gene mutations.
Conclusion. Moderately intensive warfarin therapy (international normalized ratio 2.0-3.0) could generally reduce the frequency of recurrent thrombotic events by at least 2-fold as compared with that before warfarin administration. The efficiency of using warfarin alone or in combination with aspirin in APS was found to be similar; and its safety was higher during monotherapy therefore it is undesirable to combine warfarin with antiaggregants in real clinical practice. The determination of CYP2C9 and VCORC1 genotypes in patients with APS before warfarin use allows excessive hypocoagulation and related hemorrhages to be avoided.
About the authors
Lyubov' Valer'evna Kondrat'eva
Научно-исследовательский институт ревматологии РАМН
Email: lubamoiapocta@mail.ru
канд. мед. наук, науч. сотр., лаб. системных ревматических заболеваний с группой гемореологических нарушений отдела сосудистой патологии при ревматических заболеваниях НИИР РАМН, тел.: 8-499-614-34-29; Научно-исследовательский институт ревматологии РАМН
Natal'ya L'vovna Patrusheva
Институт биоорганической химии им. акад. М. М. Шемякина и акад. Ю. А. Овчинникова РАНинженер-исследователь, лаб. биотехнологии Института биоорганической химии им. академиков М. М. Шемякина и Ю. А. Овчинникова РАН; Институт биоорганической химии им. акад. М. М. Шемякина и акад. Ю. А. Овчинникова РАН
Lev Ivanovich Patrushev
Институт биоорганической химии им. акад. М. М. Шемякина и акад. Ю. А. Овчинникова РАН
Email: patrush@mail.ibch.ru
д-р биол. наук, доц., вед. науч. сотр., лаб. биотехнологии Института биоорганической химии им. академиков М. М. Шемякина и Ю. А. Овчинникова РАН, тел.: 8-495-429-86-10; Институт биоорганической химии им. акад. М. М. Шемякина и акад. Ю. А. Овчинникова РАН
Elena Nikolaevna Aleksandrova
Научно-исследовательский институт ревматологии РАМН
Email: aleksandrovaen@irramn.ru
д-р мед. наук, зав. лаб. иммунологии и молекулярной биологии ревматических заболеваний НИИР РАМН, тел.: 8-499-615-93-77; Научно-исследовательский институт ревматологии РАМН
Tat'yana Feliksovna Kovalenko
Институт биоорганической химии им. акад. М. М. Шемякина и акад. Ю. А. Овчинникова РАН
Email: tkov@mx.ibch.ru
мл. науч. сотр., лаб. биотехнологии Института биоорганической химии им. академиков М. М. Шемякина и Ю. А. Овчинникова РАН; Институт биоорганической химии им. акад. М. М. Шемякина и акад. Ю. А. Овчинникова РАН
Ekaterina Viktorovna Ostryakova
Научно-исследовательский институт ревматологии РАМН
Email: bonbon88@yandex.ru
аспирант НИИР РАМН, тел.: 8-499-615-10-90; Научно-исследовательский институт ревматологии РАМН
Tat'yana Magomedalievna Reshetnyak
Научно-исследовательский институт ревматологии РАМН
Email: t_reshetnyak@yahoo.com
д-р мед. наук, проф., вед. науч. сотр., лаб. системных ревматических заболеваний с группой гемореологических нарушений отдела сосудистой патологии при ревматических заболеваниях НИИР РАМН, тел.: 8-499-615-93-79; Научно-исследовательский институт ревматологии РАМН
L V Kondratyeva
Research Institute of Rheumatology, Russian Academy of Medical SciencesResearch Institute of Rheumatology, Russian Academy of Medical Sciences
N L Patrusheva
Acad. M. M. Shemyakin & Acad. Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesAcad. M. M. Shemyakin & Acad. Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
L I Patrushev
Acad. M. M. Shemyakin & Acad. Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesAcad. M. M. Shemyakin & Acad. Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
E N Aleksandrova
Research Institute of Rheumatology, Russian Academy of Medical SciencesResearch Institute of Rheumatology, Russian Academy of Medical Sciences
T F Kovalenko
Acad. M. M. Shemyakin & Acad. Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of SciencesAcad. M. M. Shemyakin & Acad. Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences
E V Ostryakova
Research Institute of Rheumatology, Russian Academy of Medical SciencesResearch Institute of Rheumatology, Russian Academy of Medical Sciences
T M Reshetnyak
Research Institute of Rheumatology, Russian Academy of Medical SciencesResearch Institute of Rheumatology, Russian Academy of Medical Sciences
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