rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2003-1358rsp-1222Research ArticleСтатьиArticlesВарфарин в комплексной терапии антифосфолипидного синдрома: предварительные результатыVarfarin in the complex treatment of antiphospholipid syndrome: preliminary resultsРешетнякТ. М.ReshetnyakT M-ShirokovaI EShirokovaI E-ShtivelbandI BShtivelbandI B-LisicinaT ALisicinaT A-AleksandrovaE AAleksandrovaE A-АлександроваЕлена НиколаевнаAleksandrovaE N-200315062003413№3 (2003)3741Copyright © Решетняк Т.М., Shirokova I.E., Shtivelband I.B., Lisicina T.A., Aleksandrova E.A., Александрова Е.Н., 20032003Решетняк Т.М., Shirokova I.E., Shtivelband I.B., Lisicina T.A., Aleksandrova E.A., Александрова Е.Н.Reshetnyak T.M., Shirokova I.E., Shtivelband I.B., Lisicina T.A., Aleksandrova E.A., Aleksandrova E.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/1222

Цель. Оценить эффективность и переносимость варфарина в профилактике и терапии тромботических осложнений у больных с АФС. Материал и методы. Варфарин в течение года получали 20 больных с АФС (5 - мужчин и 15 - женщин), из которых 8-е первичным АФС (ПАФС) и 12-е системной красной волчанкой (СКВ+АФС). Еше двое больных (1- с СКВ+АФС и 1 - с ПАФС) получали варфарин последние 4 года. Никто из 9 больных с ПАФС не получал глкжокортикоиды ( ГК). У больных с СКВ+ АФС доза ГК варьировала от 4 до 20 мг/сут и не повышалась за период наблюдения. Определялось протромбиновос время (ПВ) с тромбопластином ( производства "Ренам"), имевшим международный индекс чувствительности 1,2 и международное нормализационное отношение (МНО). В зависимости от схемы терапии больные АФС были разделены на три группы: первая включала 8 пациентов с МНО <2,0, вторая- 7 с МНО > 3,0 и третья 7 больных с МНО < 2,0, получавших дополнительно тромбо АСС 100 мг/сут., и вазонит от 600 до 1200 мг/ сут. Результаты. Рецидив тромбоза ( тромбофлебит голеней имел место у 2 больных при значениях МНО = 1,8. В других группах, независимо от выраженности антикоагулянтного эффекта варфарина, рецидивов не было. У 2 больных были "большие" кровотечения. Эпизоды "малых" геморрагий были выявлены у 7. У 2 больных на фоне лечения варфарином с МНО 1.8 и 2,4 отмечался приступ почечной колики. Заключение. Предварительные результаты свидетельствуют о необходимости включения в терапию варфарина больным с АФС и тромбозами. Однако не всегда показано достижение интенсивного антикоагулянтного эффекта.

Objective. To assess efficacy and tolerance of varfarin in prophylaxis and therapy of thrombotic complications in patients with antiphospholipid syndrome (APS). Methods. 20 pts with APS (5 male and 15 female) received varfarin during a year. 8 of them had primary APS (PAPS) and 12 -systemic lupus erythematosus with APS (SLE+APS). 2 other pts (I with SLE+APS and I with PAPS) received varfarin during the last 4 years. Nobody from 9 pts with PAPS received corticosteroids (CS). In SLE+APS pts CS dose varied from 4 to 20 mg/day and was not increased during follow up. During the study prothrombine time (PT) was examined with thromboplastin ( manufactured by Renam) having international sensitivity index 1,2 and international normalization relation (INR). Depending on treatment scheme APS pts were divided into 3 groups. Group 1 included 8 pts with INR<2,0, Group 2-7 with INR >3,0, group 3 - 7 pts with INR<2,0 receiving as additional treatment thrombo ASS 100 mg/day and vasonit from 600 to 1200 mg/day. Results. Two pts with INR = 1,8 had thrombosis recurrence (due to leg thrombophlebitis). There were no recurrences in other groups. 2 from 22 pts had "large" bleedings. "Small" bleedings episodes were noted in 7 from 22 pts. Largely that were subcutaneous bleedings (in 4 pts) no more than 5 cm of size. Two pts receiving varfarin with INR 1,8 and 2,4 had renal colic. Conclusion. Our preliminary results prove the necessity of inclusion of varfarin in the treatment of pts with APS and thrombosis but intensive anticoagulant effect is not always desired.

антифосфолипидный синдромварфаринantipliospholipid syndromeVarfarinReferences<div><p>Баркаган З.С., Мамот А.П. Диагностика и контролируемая терапия нарушений гемостаза. М, 2001,</p><p>Насонов ЕЛ. Алекберова З.С., Александрова Е.Н. и соавт. Антитела к кардиолипину: метод определения и клиническое значение. Клин.мед 1987, II, 100-104.</p><p>Исследование гемостаза (пособие для врачей-лаборан- тов по методам). Составители: Козлов АЛ., Берковский А.Л., Качалова Н.Д., Простакова Т.М. 14-23. М., 2003.</p><p>Altman R. Rouvier J,, Gurfinkel E. et al. Comparison of two levels of anticoagulant therapy in patients with substitute heart valves. J. Thorac. Cardiovasc. Surg., 1991, 101.427- 431.</p><p>Ames P.R., Ciampa A., Grandone E. et al. Conventional oral anticoagulation (INR2-3) effectively prevents rethrombosis in primary antiphospholipid syndrome. Lupus, 2002, 9, 624 (abstr).</p><p>Beyth R.J., Quinn L.M., Landfeld C.S. Prospective evalu- tion of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am. J. Med., 1998, 105, 91-99.</p><p>Exner Т., Rickard K.A., Kronenberg H. Studies on phospholipids in the action of a lupus anticoagulation inhibitor. Pathology. 1975, 7, 319-328.</p><p>Film S.D. McDonell М., Martin D. et al. Risk factors for complications of chronic anticoagulation: a multicemer study. Ann. Intern. Med. 1993, 118, 511-520.</p><p>Hylek E.M., Singer D.E. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann. Intern. Med. 1994,120,897-902.</p><p>Hull R., Hirsh J, Jay R, et al. Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis. N. Engl. J. Med., 1982, 307,1676 -1681.</p><p>Khamashta M.A., Cuadrado M.J. Mujic F. et al. The management of thrombosis in the antiphospholipid antibody syndrome. N.Engl. J. Med., 1995. 332(15). 993-997.</p><p>Kearon C., Gent М., Hirsh J. et al. A comparison of three month of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N.Engl.J.Med., 1999, 340, 901-907.</p><p>Landefeld C.S., Goldman L. Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy. Am. J. Med., 1989, 87,144 -152.</p><p>Magaglione М., Colaizzo D., Andrea G.D. et al. Genetic modulation of oral anticoagulation with warfarin. Thromb. Haemost., 2000, 84, 775-778,</p><p>Ridker P.M., Goldhaber S.Z., Dunielson E, et al. Longterm, low-intensity warfarin for the preventation of recurrent venous thromboembolism. The New Engl. J. Med., 2003, 348,15.</p><p>Ruiz-irastorza G., Khamashta M.A., Hunt B.J. et al. Bleeding and recurrent thrombosis in definite antiphospholipid syndrome: analysis of a series of 66 patients treated with oral anticoagulation to a target international normalized ratio of 3,5. Arch. Intern. Med., 2002, 162(10), 11641169.</p><p>Saour J.N. Sieck J.O. Mamo L.A.R. et al. Trial of different intensities of anticoagulation in patients with prosthetic heart valves. N. Engl. J. Med., 1990. 322, 28 -432.</p><p>Steward D.J., Haining R.L., Henne K.R. et al. Genetic association between sensivity to warfarin and expression of CYPC9*3. Pharmacogenetics. 1997. 7, 361-367.</p><p>Tan E.M. Cohen A.S. Fries J.S. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arth. Rheum., 1982, 25, 1271-77.</p><p>Turpie A.G.G., Gunstensen J., Hirsh J. et al. Randomized comparison of two intensities of oral anticoagulant therapy after tissue heart valve replacement. Lancet, 1988, 1,12421245.</p><p>Walker J.t Mendelson H., McClure A.Smith M.D. Warfarin and azatioprine: clically significant drug interaction (letter). J.Rheumatol., 2002, 29. 398-399.</p><p>Wells P.S., Holbrook A.M., Crowthcr N.R., Hirsh J. Interaction of warfarin with dmgs and food. Ann.Intern.Med., 1994, 121. 676-683.</p><p>Wilson W.A., Gharavi A.E., Koike T. et al.International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome. Arthr. Rheum., 1999, 42, 1309-1311.</p></div><br /><div><p>Баркаган З.С., Мамот А.П. Диагностика и контролируемая терапия нарушений гемостаза. М, 2001,</p><p>Насонов ЕЛ. Алекберова З.С., Александрова Е.Н. и соавт. Антитела к кардиолипину: метод определения и клиническое значение. Клин.мед 1987, II, 100-104.</p><p>Исследование гемостаза (пособие для врачей-лаборан- тов по методам). Составители: Козлов АЛ., Берковский А.Л., Качалова Н.Д., Простакова Т.М. 14-23. М., 2003.</p><p>Altman R. Rouvier J,, Gurfinkel E. et al. Comparison of two levels of anticoagulant therapy in patients with substitute heart valves. J. Thorac. Cardiovasc. Surg., 1991, 101.427- 431.</p><p>Ames P.R., Ciampa A., Grandone E. et al. Conventional oral anticoagulation (INR2-3) effectively prevents rethrombosis in primary antiphospholipid syndrome. Lupus, 2002, 9, 624 (abstr).</p><p>Beyth R.J., Quinn L.M., Landfeld C.S. Prospective evalu- tion of an index for predicting the risk of major bleeding in outpatients treated with warfarin. Am. J. Med., 1998, 105, 91-99.</p><p>Exner Т., Rickard K.A., Kronenberg H. Studies on phospholipids in the action of a lupus anticoagulation inhibitor. Pathology. 1975, 7, 319-328.</p><p>Film S.D. McDonell М., Martin D. et al. Risk factors for complications of chronic anticoagulation: a multicemer study. Ann. Intern. Med. 1993, 118, 511-520.</p><p>Hylek E.M., Singer D.E. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann. Intern. Med. 1994,120,897-902.</p><p>Hull R., Hirsh J, Jay R, et al. Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis. N. Engl. J. Med., 1982, 307,1676 -1681.</p><p>Khamashta M.A., Cuadrado M.J. Mujic F. et al. The management of thrombosis in the antiphospholipid antibody syndrome. N.Engl. J. Med., 1995. 332(15). 993-997.</p><p>Kearon C., Gent М., Hirsh J. et al. A comparison of three month of anticoagulation with extended anticoagulation for a first episode of idiopathic venous thromboembolism. N.Engl.J.Med., 1999, 340, 901-907.</p><p>Landefeld C.S., Goldman L. Major bleeding in outpatients treated with warfarin: incidence and prediction by factors known at the start of outpatient therapy. Am. J. Med., 1989, 87,144 -152.</p><p>Magaglione М., Colaizzo D., Andrea G.D. et al. Genetic modulation of oral anticoagulation with warfarin. Thromb. Haemost., 2000, 84, 775-778,</p><p>Ridker P.M., Goldhaber S.Z., Dunielson E, et al. Longterm, low-intensity warfarin for the preventation of recurrent venous thromboembolism. The New Engl. J. Med., 2003, 348,15.</p><p>Ruiz-irastorza G., Khamashta M.A., Hunt B.J. et al. Bleeding and recurrent thrombosis in definite antiphospholipid syndrome: analysis of a series of 66 patients treated with oral anticoagulation to a target international normalized ratio of 3,5. Arch. Intern. Med., 2002, 162(10), 11641169.</p><p>Saour J.N. Sieck J.O. Mamo L.A.R. et al. Trial of different intensities of anticoagulation in patients with prosthetic heart valves. N. Engl. J. Med., 1990. 322, 28 -432.</p><p>Steward D.J., Haining R.L., Henne K.R. et al. Genetic association between sensivity to warfarin and expression of CYPC9*3. Pharmacogenetics. 1997. 7, 361-367.</p><p>Tan E.M. Cohen A.S. Fries J.S. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arth. Rheum., 1982, 25, 1271-77.</p><p>Turpie A.G.G., Gunstensen J., Hirsh J. et al. Randomized comparison of two intensities of oral anticoagulant therapy after tissue heart valve replacement. Lancet, 1988, 1,12421245.</p><p>Walker J.t Mendelson H., McClure A.Smith M.D. Warfarin and azatioprine: clically significant drug interaction (letter). J.Rheumatol., 2002, 29. 398-399.</p><p>Wells P.S., Holbrook A.M., Crowthcr N.R., Hirsh J. Interaction of warfarin with dmgs and food. Ann.Intern.Med., 1994, 121. 676-683.</p><p>Wilson W.A., Gharavi A.E., Koike T. et al.International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome. Arthr. Rheum., 1999, 42, 1309-1311.</p></div><br />

The authors declare that there are no conflicts of interest present.