tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2014-3-147-154tumors-84Research ArticleОБЗОРЫ И АНАЛИТИКАREVIEWS AND ANALYSISГИПОФИБРИНОЛИЗ КАК ОСНОВНОЙ ФАКТОР РИСКА ТРОМБОЭМБОЛИЧЕСКИХ ОСЛОЖНЕНИЙ У ОНКОЛОГИЧЕСКИХ ПАЦИЕНТОВHypofibrinolysis as a major factor risk of thromboembolic events in cancer patientsПетроваО. Ю.PetrovaO. Yu.

Контактная информация: Петрова Ольга Юрьевна, ГБУЗ СО «СООД», olgapetrova@mail.ru, +79193768288

olgapetrova@mail.ruСухановВ. А.SukhanovV. A.

уханов Владимир Александрович, ГБУЗ СО «СОКБ  № 1», valex.s@mail.ru, +79221490722

valex.s@mail.ruЛевитД. А.LevitD. A.

Левит  Дмитрий  Александрович, ГБУЗ СО «СОКБ  № 1», lal@okb1.ru, +79222022212

lal@okb1.ruСвердловский областной онкологический диспансерг, ЕкатеринбургRussian FederationСвердловская областная клиническая больница №1Russian Federation20142105201503147154Copyright © Петрова О.Ю., Суханов В.А., Левит Д.А., 20152015Петрова О.Ю., Суханов В.А., Левит Д.А.Petrova O.Y., Sukhanov V.A., Levit D.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.malignanttumors.org/jour/article/view/84Введение

Введение: Частота венозных тромбоэмболических  осложнений (ВТЭО) у онкологических пациентов (ОП) увеличивается на 10% во время химиотерапии (ХТ). Сочетание системной гиперкоагуляции крови и гипофибринолиза являются наиболее опасными рисками ВТЭО.

Целью данного исследования было оценить параметры тромбоэластографии  (ТЭГ) (гиперкоагуляция и гипофибринолиз) для оценки антитромботического эффекта низкомолекулярного гепарина (НМГ).

Методы

Методы: Мы изучали 78 ОП (женщины – 47, средний возраст – 56 лет) с высоким  риском  ВТЭО по шкале Khorana до ХТ (≥3 балла). Исследования крови делали до и через 3–4 часа  после  инъекции  НМГ (дальтепарин  натрий 5000 МЕ в сутки). Изучали следующие ТЭГ параметры  (TEG 5000,  США): R – время начала реакции (наша модификация, патент РФ № 2015515, норма=660–970 с), фибринолиз (наша модификация,  патент РФ № 2358657, норма=60–120%).  Чтобы оценить комплексно взаимодействие этих двух параметров, мы решили ввести бальную оценку. Мы присвоили:  1 балл когда параметр R был менее 500 сек и 1 балл при фибринолизе  менее 40%. В случае укорочения этих показателей  ниже означенных значений начинали терапию НМГ.

Результаты

Результаты:  До назначения НМГ в 38% ОП имели умеренную/выраженную гиперкоагуляцию крови (средний балл=0,5),  и в 80% – умеренное/выраженное угнетение фибринолиза (средний балл = 0,95): общий балл (ОБ) составил 1,45. Следовательно, угнетение фибринолиза является ведущим фактором риска ВТЭО у ОП. На пике действия НМГ ОБ снизился на 64% (р <0,01).  У 10% больных с ОБ = 1,0 мы увеличили дозу  НМГ до 5000  МЕ х 2 раза в день. В результате,  контроль параметров ТЭГ показал сокращение ОБ на 14% от первоначального. Таким образом,  дополнительная медикаментозная  коррекция системы гемостаза и фибринолиза  снижает ОБ на 78% от первоначального.

Выводы

Выводы:  Гипофибринолиз является одним из основных рисков ВТЭО. Комбинированная  оценка гиперкоагуляции  крови и гипофибринолиза  позволит  лучше оценить  риск развития  ВТЭО у ОП. Предлагаемые параметры ТЭГ являются наиболее подходящими для оценки антитромботического эффекта НМГ.

Introduction

Introduction: The frequency of venous thromboembolic complications (VTEC) in cancer patients increased by 10% during chemotherapy. The combination of systemic hypercoagulation and hypofibrinolysis are the most dangerous risk factors of VTEC.

Aim of this study was to evaluate the parameters of thromboelastography (hypercoagulation and hypofibrinolisis) to assess the impact of the use of low molecular weight heparin.

Methods

Methods: We studied 78 cancer patients (women - 47, average age - 56 years) before chemotherapy with a high risk of VTEC according to Khorana scale (≥3 points). Blood tests were taken before and 3-4 hours after injection of LMWH (dalteparin sodium 5000 IU per day). The following parameters of thromboelastography were studied (TEG 5000, USA): R - the start of the reaction (our modification, RF patent №2015515, normal values = 660-970), fibrinolysis (our modification, RF patent №2358657, normal values = 60-120%). To evaluate the complex interaction of these two parameters, we decided to introduce a point scoring: 1 point when the parameter R was less than 500 seconds and 1 point when fibrinolysis was lower 40%. In case of reduction of these parameters above the a/n values we began therapy with LMWH.

Results

Results: Before the use of LMWH 38% of cancer patients had moderate/expressed hypercoagulation (mean score = 0.5), and 80% - moderate/expressed inhibition of fibrinolysis (average score = 0.95); total score was 1.45. Therefore, inhibition of fibrinolysis is a leading risk factor for VTEC in cancer patients. At the peak of the action of LMWH total score decreased by 64% (p <0.01). In 10% of patients with total score = 1.0, we increased dose up to 5000 IU LMWH x 2 times per day. As a result, the control of tromboelastography parameters showed a reduction of total score by 14% of the initial value. Thus, additional drug correction of the hemostatic system and fibrinolysis reduced total score by 78% of the initial value.

Conclusion

Conclusion: Hypofibrinolysis is a major risk factor of VTEC development. Combined evaluation of hypercoagulation and hypofibrinolysis allows a better assessment of the risk of VTEC in cancer patients. The proposed parameters of thromboelastography are the most appropriate for the evaluation of LMWH antithrombotic effect.

онкологиявенозная тромбоэмболияхимиотерапиятромбоэластографиянизкомолекулярный гепаринoncologyvenous thromboembolismchemotherapythromboelastographylow molecular weight heparinReferencesBoillaud J. B. De la obliteration des veines et de son influence sur la formation des hidropisies partielles: consideration sur la hydropisies passive et general // Arch. Gen. Med. – 1823 – Vol. 1 – P. 188–204.Boillaud J. B. De la obliteration des veines et de son influence sur la formation des hidropisies partielles: consideration sur la hydropisies passive et general // Arch. Gen. Med. – 1823 – Vol. 1 – P. 188–204.Trousseau A. Phlegmasia Alba Dolens // In.: Balliere J. B. Ed. Clinique Medicale de 1’Hotel Dieu de Paris, 2nd edition. Paris, Balliere.– 1865.– Vol. 3: – P 654–712.Trousseau A. Phlegmasia Alba Dolens // In.: Balliere J. B. Ed. Clinique Medicale de 1’Hotel Dieu de Paris, 2nd edition. Paris, Balliere.– 1865.– Vol. 3: – P 654–712.Billroth T. Lectures on surgical pathology and therapeutics: a handbook for students and practitioners. // 8th ed. London: The New Sydenham Society – 1878. – P. 1877–8.Billroth T. Lectures on surgical pathology and therapeutics: a handbook for students and practitioners. // 8th ed. London: The New Sydenham Society – 1878. – P. 1877–8.Баркаган З. С. Патогенез и терапия нарушений гемостаза у онкологических больных // Поддерживающая терапия у онкологических больных. Европейская школа по онкологии / Под ред. Личиницер М. – М.: Арго, 1996. – С. 217–224.Баркаган З. С. Патогенез и терапия нарушений гемостаза у онкологических больных // Поддерживающая терапия у онкологических больных. Европейская школа по онкологии / Под ред. Личиницер М. – М.: Арго, 1996. – С. 217–224.Фокин А. А., Важенин А. В. Венозный тромбоэмболический синдром у онкологических больных: диагностическое значение и меры профилактики // Третья конференция ассоциации флебологов России: Материалы. Ростов-на-Дону, 2001.– С. 186.Фокин А. А., Важенин А. В. Венозный тромбоэмболический синдром у онкологических больных: диагностическое значение и меры профилактики // Третья конференция ассоциации флебологов России: Материалы. Ростов-на-Дону, 2001.– С. 186.Monreal M., Fernandez-Llamazares J., Perandreu J. et al. Occult cancer in patients with venous thromboembolism: which patients, which cancers // Thromb. Haemost. – 1997. – Vol. 78 (5). – P. 1316–1318.Monreal M., Fernandez-Llamazares J., Perandreu J. et al. Occult cancer in patients with venous thromboembolism: which patients, which cancers // Thromb. Haemost. – 1997. – Vol. 78 (5). – P. 1316–1318.Heit J. A., O’Fallon W.M., Petterson T. M. et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study // Arch. Intern. Med. – 2002. – Vol. 162 (11). – P. 1245–1248.Heit J. A., O’Fallon W.M., Petterson T. M. et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study // Arch. Intern. Med. – 2002. – Vol. 162 (11). – P. 1245–1248.Khorana A. A. Venous thromboembolism and prognosis in cancer // Thromb. Res. – 2010. – Vol. 125 (6). – P. 490–493.Khorana A. A. Venous thromboembolism and prognosis in cancer // Thromb. Res. – 2010. – Vol. 125 (6). – P. 490–493.Баркаган З. С. Патогенез и терапия нарушений гемостаза у онкологических больных // Поддерживающая терапия у онкологических больных. Европейская школа по онкологии / Под ред. Личиницер М. – М.: Арго, 1996. – С. 217–224.Баркаган З. С. Патогенез и терапия нарушений гемостаза у онкологических больных // Поддерживающая терапия у онкологических больных. Европейская школа по онкологии / Под ред. Личиницер М. – М.: Арго, 1996. – С. 217–224.Nadir Y., Hoffman R., Brenner B: Drug-related thrombosis in hematologic malignancies // Rev. Clin. Exp. Hematol. – 2004. – Vol. 8 (1). – E. 4.Nadir Y., Hoffman R., Brenner B: Drug-related thrombosis in hematologic malignancies // Rev. Clin. Exp. Hematol. – 2004. – Vol. 8 (1). – E. 4.Silverstein M. D., Heit J. A., Mohr D. N. et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study // Arch. Intern. Med. – 1998. – Vol. 158. – P. 585–593.Silverstein M. D., Heit J. A., Mohr D. N. et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study // Arch. Intern. Med. – 1998. – Vol. 158. – P. 585–593.Moor RA, Adel N, Riedel E, et al. High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: a large retrospective analysis // J. Clin. Oncol. – 2011. Vol. 29. – P. 3466–73.Moor RA, Adel N, Riedel E, et al. High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: a large retrospective analysis // J. Clin. Oncol. – 2011. Vol. 29. – P. 3466–73.Heit J. A., Silverstein M. D., Mohr D. N. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study // Arch. Intern. Med. – 2000. Vol. 160. – P. 809–815.Heit J. A., Silverstein M. D., Mohr D. N. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study // Arch. Intern. Med. – 2000. Vol. 160. – P. 809–815.Levine M. N., Gent M., Hirsh J. et al. The thrombogenic effect of anticancer drug therapy in women with stage II breast cancer // N. Engl. J. Med. – 1988. – Vol. 318. – P. 404–407.Levine M. N., Gent M., Hirsh J. et al. The thrombogenic effect of anticancer drug therapy in women with stage II breast cancer // N. Engl. J. Med. – 1988. – Vol. 318. – P. 404–407.Saphner T., Tormey D. C., Gray R. Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer // J. Clin. Oncol. – 1991. – Vol. 9. – P. 286–294.Saphner T., Tormey D. C., Gray R. Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer // J. Clin. Oncol. – 1991. – Vol. 9. – P. 286–294.Khorana A. A., Dalal M., Connolly G. C. et al. Incidence and Predictors of Venous Thromboembolism (VTE) Among Ambulatory High-Risk Cancer Patients Undergoing Chemotherapy in the United States // http://onlinelibrary. wiley.com/doi/10.1002/cncr.27772/pdf.Khorana A. A., Dalal M., Connolly G. C. et al. Incidence and Predictors of Venous Thromboembolism (VTE) Among Ambulatory High-Risk Cancer Patients Undergoing Chemotherapy in the United States // http://onlinelibrary. wiley.com/doi/10.1002/cncr.27772/pdf.Swystun L. L. Modulation of hemostatic pathways by breast cancer chemotherapy agents // A Thesis for the Degree Doctor of Philosophy. McMaster University. August, 2011.Swystun L. L. Modulation of hemostatic pathways by breast cancer chemotherapy agents // A Thesis for the Degree Doctor of Philosophy. McMaster University. August, 2011.Khorana A. A., Francis C. W., Culakova E. et al. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy // J. Thromb. Haemost. – 2007. – Vol. 5 (3). – P. 632–634.Khorana A. A., Francis C. W., Culakova E. et al. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy // J. Thromb. Haemost. – 2007. – Vol. 5 (3). – P. 632–634.S rensen H. T., Mellemkj r L., Olsen J. H. et al. Prognosis of cancers associated with venous thromboembolism // N. Engl. J. M. – 2000. Vol. 343 (25). – P. 1846–1850.S rensen H. T., Mellemkj r L., Olsen J. H. et al. Prognosis of cancers associated with venous thromboembolism // N. Engl. J. M. – 2000. Vol. 343 (25). – P. 1846–1850.NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Cancer-Associated Venous Thromboembolic Disease. Version 1.201.NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Cancer-Associated Venous Thromboembolic Disease. Version 1.201.McKarney L. Advances in the Treatment of Metastatic Colorectal Cancer // NE Oncology Issue – 2006 // http://www.newevidence.com/oncology/entries/ Advances_in_the_Treatment_of_Metastatic/McKarney L. Advances in the Treatment of Metastatic Colorectal Cancer // NE Oncology Issue – 2006 // http://www.newevidence.com/oncology/entries/ Advances_in_the_Treatment_of_Metastatic/Fitch K. and Pyenson B. Cancer Patients Receiving Chemotherapy: Opportunities for Better Management // http://publications.milliman.com/research/health-rr/pdfs/ cancer-patients-receiving-chemotherapy.pdf.Fitch K. and Pyenson B. Cancer Patients Receiving Chemotherapy: Opportunities for Better Management // http://publications.milliman.com/research/health-rr/pdfs/ cancer-patients-receiving-chemotherapy.pdf.Khorana A. A., Conolly G. C. Assessing risk of venous thromboembolism in the patients with cancer // J. Clin. Oncol. – 2009. – Vol. 27 (29). – P. 4839–4847.Khorana A. A., Conolly G. C. Assessing risk of venous thromboembolism in the patients with cancer // J. Clin. Oncol. – 2009. – Vol. 27 (29). – P. 4839–4847.Khorana A. A., Francis C. W., Culacova E. et al. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients // Cancer. – 2007. Vol. – 110. P. 2339–2346.Khorana A. A., Francis C. W., Culacova E. et al. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients // Cancer. – 2007. Vol. – 110. P. 2339–2346.Khorana A. A., Kuderer N. M., Culacova E. et al. Development and validation of a predictive model for chemotherapy-associated thrombosis // Blood. – 2008. – Vol. 111. – P. 4902–4907.Khorana A. A., Kuderer N. M., Culacova E. et al. Development and validation of a predictive model for chemotherapy-associated thrombosis // Blood. – 2008. – Vol. 111. – P. 4902–4907.Heit J. A., Mohr D. N., Silverstein M. D. et al. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study // Arch. Intern. Med. – 2000. – Vol. 160. – P 761–768.Heit J. A., Mohr D. N., Silverstein M. D. et al. Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study // Arch. Intern. Med. – 2000. – Vol. 160. – P 761–768.Kr ger K., Weiland D., Ose C. et al. Risk factors for venous thromboembolic events in cancer patients // Ann. Oncol. – 2006. – Vol. 17. – P.297–303.Kr ger K., Weiland D., Ose C. et al. Risk factors for venous thromboembolic events in cancer patients // Ann. Oncol. – 2006. – Vol. 17. – P.297–303.Mandala M, Clerici M, Corradino I, et al. Incidence, risk factors and clinical implications of venous thromboembolism in cancer patients treated within the context of phase I studies: the «SENDO experience» // Ann. Oncol. – 2012. Vol. 23. P. 1416–1421.Mandala M, Clerici M, Corradino I, et al. Incidence, risk factors and clinical implications of venous thromboembolism in cancer patients treated within the context of phase I studies: the «SENDO experience» // Ann. Oncol. – 2012. Vol. 23. P. 1416–1421.Tateo S., Mereu L., Salamano S. et al. Ovarian cancer and venous thromboembolic risk // Ginecol. Oncol. – 2005. Vol. 99. – P. 119–25.Tateo S., Mereu L., Salamano S. et al. Ovarian cancer and venous thromboembolic risk // Ginecol. Oncol. – 2005. Vol. 99. – P. 119–25.Chew H. K., Wun T., Harvey D., et al. Incidence of venous thromboembolism and its effect on survival among patients with common cancers // Arch. Intern. Med. – 2006. Vol. 166 (4). – P. 458–64.Chew H. K., Wun T., Harvey D., et al. Incidence of venous thromboembolism and its effect on survival among patients with common cancers // Arch. Intern. Med. – 2006. Vol. 166 (4). – P. 458–64.Khorana A. A., Francis C. W., Culacova E. et al. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy // J. Thromb. Haemost. – 2007. – Vol. 5. – P. 632–4.Khorana A. A., Francis C. W., Culacova E. et al. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy // J. Thromb. Haemost. – 2007. – Vol. 5. – P. 632–4.Wun T., White R. H. Epidemiology of cancer-related venous thromboembolism // Best. Pr. Res. Clin. Haematol. – 2009. Vol. 22. – P. 9–23.Wun T., White R. H. Epidemiology of cancer-related venous thromboembolism // Best. Pr. Res. Clin. Haematol. – 2009. Vol. 22. – P. 9–23.Blom J., Doggen C. Malignancies, prothrombotic mutation, and the risk of venous thrombosis // JAMA. – 2005. – Vol. 293. – P.715–722.Blom J., Doggen C. Malignancies, prothrombotic mutation, and the risk of venous thrombosis // JAMA. – 2005. – Vol. 293. – P.715–722.Ahlbrecht J., Dickmann B., Ay C. et al. Tumor grade is associated with venous thromboembolism in patients with cancer: results the Vienna Cancer and Thrombosis Study // J. Clin. Oncol. – 2012. Vol. 30. – P. 3870–5.Ahlbrecht J., Dickmann B., Ay C. et al. Tumor grade is associated with venous thromboembolism in patients with cancer: results the Vienna Cancer and Thrombosis Study // J. Clin. Oncol. – 2012. Vol. 30. – P. 3870–5.Dickmann B., Ahlbrecht J., Ay C. et al. Regional lymph node metastases are strong risk factor for venous thromboembolism: results from the Vienna Cancer and Thrombosis Study // Haematologica.– 2013. Vol. 98. P. 1309–1314.Dickmann B., Ahlbrecht J., Ay C. et al. Regional lymph node metastases are strong risk factor for venous thromboembolism: results from the Vienna Cancer and Thrombosis Study // Haematologica.– 2013. Vol. 98. P. 1309–1314.Surgical wound healing complications in metastatic colorectal cancer patients with bevacizumab // J. Surg. Oncol. – 2005. – Vol. 91. – P. 173–180.Surgical wound healing complications in metastatic colorectal cancer patients with bevacizumab // J. Surg. Oncol. – 2005. – Vol. 91. – P. 173–180.Choueri T. K., Schutz F. A., Je Y. et al. Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials // J. Clin. Oncol. – 2010. – Vol. 28. – P. 2280–2285.Choueri T. K., Schutz F. A., Je Y. et al. Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials // J. Clin. Oncol. – 2010. – Vol. 28. – P. 2280–2285.Cavo M., Zamagni E, Cellini C. et al. Deep-vein thrombosis in patients with multiple myeloma receiving first-line thalidomide-dexamethasone therapy // Blood. – 2002. – Vol. 100. – P. 2272–2273.Cavo M., Zamagni E, Cellini C. et al. Deep-vein thrombosis in patients with multiple myeloma receiving first-line thalidomide-dexamethasone therapy // Blood. – 2002. – Vol. 100. – P. 2272–2273.Petrelli F., Cabiddu M., Borgonovo K. et al. Risk of venous and arterial thromboembolic events associated with anti-EGFR agents: a meta-analysis of randomized clinical trials // Ann. Oncol. – 2012. Vol. 23. – P.1672–1679.Petrelli F., Cabiddu M., Borgonovo K. et al. Risk of venous and arterial thromboembolic events associated with anti-EGFR agents: a meta-analysis of randomized clinical trials // Ann. Oncol. – 2012. Vol. 23. – P.1672–1679.Pabinger I., Thaler J., Ay C. Biomarkers for prediction of venous thromboembolism in cancer // Blood. – 2013. – Vol. 122. – P. 2011–2018.Pabinger I., Thaler J., Ay C. Biomarkers for prediction of venous thromboembolism in cancer // Blood. – 2013. – Vol. 122. – P. 2011–2018.Khorana A. A., McCrae K. R. Risk stratification strategies for cancer-associated thrombosis: an update // Thromb. Res. – 2014. – Vol. 133 (S2). – P 35–38.Khorana A. A., McCrae K. R. Risk stratification strategies for cancer-associated thrombosis: an update // Thromb. Res. – 2014. – Vol. 133 (S2). – P 35–38.Lyman G. H., Khorana A. A., Kuderer N. M. et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update // J. Clin. Oncol. – 2013. – Vol. 31. P. 2189–2204.Lyman G. H., Khorana A. A., Kuderer N. M. et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update // J. Clin. Oncol. – 2013. – Vol. 31. P. 2189–2204.RUSSCO. Практические рекомендации по профилактике и лечению тромбоэмболических осложнений у онкологических больных // Практические рекомендации.– Версия 2013.– С.372–376.RUSSCO. Практические рекомендации по профилактике и лечению тромбоэмболических осложнений у онкологических больных // Практические рекомендации.– Версия 2013.– С.372–376.Ay C., Dunkler D., Marosi C. et al. Prediction of venous thromboembolism in cancer patients // Blood. – 2010.– Vol. 116.– P. 5377–5382.Ay C., Dunkler D., Marosi C. et al. Prediction of venous thromboembolism in cancer patients // Blood. – 2010.– Vol. 116.– P. 5377–5382.K nigsbr gge O., Pabinger I., Ay C. Risk factors for venous thromboembolism in cancer: novel findings from the Vienna Cancer and Thrombosis Study (CATS) // Thromb. Res. – 2014. – Vol. 133 (S2). – P. 39–43.K nigsbr gge O., Pabinger I., Ay C. Risk factors for venous thromboembolism in cancer: novel findings from the Vienna Cancer and Thrombosis Study (CATS) // Thromb. Res. – 2014. – Vol. 133 (S2). – P. 39–43.Verso M., Agnelli G., Barni S. et al. A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the Protecht score // Intern. Emerg. Med. – 2012. – Vol. 7. – P. 291–292.Verso M., Agnelli G., Barni S. et al. A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the Protecht score // Intern. Emerg. Med. – 2012. – Vol. 7. – P. 291–292.translate.academic.rutranslate.academic.ruШилова Ю. Н., Шилова А. Н., Кармадонова Н. А. и др. Изменение показателей коагуляционного гемостаза у онкологических больных // Сибирский онкологический журнал. – 2013. – Приложение 1.Шилова Ю. Н., Шилова А. Н., Кармадонова Н. А. и др. Изменение показателей коагуляционного гемостаза у онкологических больных // Сибирский онкологический журнал. – 2013. – Приложение 1.Sun N. C., McAfee W.M., Hum G. J. Hemostatic abnormalities in malignancy, a prospective study of one hundred eight patients. Part I. Coagulation studies // Am. J. Clin. Pathol. – 1979. – Vol. 7. – P. 10–6.Sun N. C., McAfee W.M., Hum G. J. Hemostatic abnormalities in malignancy, a prospective study of one hundred eight patients. Part I. Coagulation studies // Am. J. Clin. Pathol. – 1979. – Vol. 7. – P. 10–6.Nand S, Fisher SG, Salgia R, Fisher RI. Hemostatic abnormalities in untreated cancer: incidence and correlation with thrombotic and hemorrhagic complications // J. Clin. Oncol. – 1987. – Vol. 5. – P. 1998–2003.Nand S, Fisher SG, Salgia R, Fisher RI. Hemostatic abnormalities in untreated cancer: incidence and correlation with thrombotic and hemorrhagic complications // J. Clin. Oncol. – 1987. – Vol. 5. – P. 1998–2003.Buccheri G., Ferrigno D., Ginardi C. et al. Haemostatic abnormalities in lung cancer: prognostic implications // Eur. J. Cancer. – 1997. – Vol. 33. – P. 50–55.Buccheri G., Ferrigno D., Ginardi C. et al. Haemostatic abnormalities in lung cancer: prognostic implications // Eur. J. Cancer. – 1997. – Vol. 33. – P. 50–55.Johnson M.J, Walker I. D., Sproule M. W. et al. Abnormal coagulation and deep venous thrombosis in patients with advanced cancer // Clin. Lab. Haematol. – 1999. – Vol. 21. – P. 51–54.Johnson M.J, Walker I. D., Sproule M. W. et al. Abnormal coagulation and deep venous thrombosis in patients with advanced cancer // Clin. Lab. Haematol. – 1999. – Vol. 21. – P. 51–54.Sallah S., Wan J. Y., Nguyen N. P. et al. Disseminated intravascular coagulation in solid tumors: clinical and pathologic study // Thromb. Haemost. – 2001. – Vol. 86. – P. 828–233.Sallah S., Wan J. Y., Nguyen N. P. et al. Disseminated intravascular coagulation in solid tumors: clinical and pathologic study // Thromb. Haemost. – 2001. – Vol. 86. – P. 828–233.Sallah S, Husain A, Sigounas V et al. Plasma coagulation markers in patients with solid tumors and venous thromboembolic disease receiving oral anticoagulation therapy // Clin. Cancer. Res. – 2004. – Vol. 10. – P. 7238–7243.Sallah S, Husain A, Sigounas V et al. Plasma coagulation markers in patients with solid tumors and venous thromboembolic disease receiving oral anticoagulation therapy // Clin. Cancer. Res. – 2004. – Vol. 10. – P. 7238–7243.Miller G. J., Bauer K. A., Howarth D. J. et al. Increased incidence of neoplasia of the digestive tract in men with persistent activation of the coagulant pathway // J. Thromb. Haemost. – 2004. – Vol 2. – P. 2107–2114.Miller G. J., Bauer K. A., Howarth D. J. et al. Increased incidence of neoplasia of the digestive tract in men with persistent activation of the coagulant pathway // J. Thromb. Haemost. – 2004. – Vol 2. – P. 2107–2114.Суханов В. А. и др. Принципы мониторинга системы гемостаза и медикаментозной коррекции свертывания крови у реанимационных больных // Интенсивная терапия. – 2009. – 3 (17) – C. 176–178.Суханов В. А. и др. Принципы мониторинга системы гемостаза и медикаментозной коррекции свертывания крови у реанимационных больных // Интенсивная терапия. – 2009. – 3 (17) – C. 176–178.Haas C. E. Monitoring Anticoagulation Therapy in the Critically Ill // The Society of Critical Care Medicine (SCCM). – April 2008.Haas C. E. Monitoring Anticoagulation Therapy in the Critically Ill // The Society of Critical Care Medicine (SCCM). – April 2008.Суханов В. А., Петрова О.Ю, Левит А. Л. Значение клинической гемостазиологии в интенсивной терапии // Интенсивная терапия и анестезия. – 2014. – № .1 (6). – С. 43–46.Суханов В. А., Петрова О.Ю, Левит А. Л. Значение клинической гемостазиологии в интенсивной терапии // Интенсивная терапия и анестезия. – 2014. – № .1 (6). – С. 43–46.Moore H. B., Moore E. E., Gonzalez E. et al. Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: The spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy // J. Trauma Acute Care. Surg. – 2014. – Vol. 21. – Epub ahead of print.Moore H. B., Moore E. E., Gonzalez E. et al. Hyperfibrinolysis, physiologic fibrinolysis, and fibrinolysis shutdown: The spectrum of postinjury fibrinolysis and relevance to antifibrinolytic therapy // J. Trauma Acute Care. Surg. – 2014. – Vol. 21. – Epub ahead of print.Sukhanov V. A., Petrova O. Y. Application of thromboelastography parameters for the prediction of venous thromboembolism in cancer patients receiving chemotherapy // Thromb. Res.– 2014.– Vol. 133 (S2).– S 203.Sukhanov V. A., Petrova O. Y. Application of thromboelastography parameters for the prediction of venous thromboembolism in cancer patients receiving chemotherapy // Thromb. Res.– 2014.– Vol. 133 (S2).– S 203.Rickles F. R., Falanga A. Activation of clotting factors in cancer // Cancer Treat. Res. – 2009. – Vol. 148. – P. 31–41.Rickles F. R., Falanga A. Activation of clotting factors in cancer // Cancer Treat. Res. – 2009. – Vol. 148. – P. 31–41.Falanga A., Russo L. Epidemiology, risk and outcomes of venous thromboembolism in cancer // Hamostaseologie. – 2012. – Vol. 32. – P. 115–125.Falanga A., Russo L. Epidemiology, risk and outcomes of venous thromboembolism in cancer // Hamostaseologie. – 2012. – Vol. 32. – P. 115–125.Falanga A., Tartari C.J,. Marchetti M.. Microparticles in tumor progression // Thromb. Res. – 2012. – Vol. 129 (Suppl. 1). – S132–6.Falanga A., Tartari C.J,. Marchetti M.. Microparticles in tumor progression // Thromb. Res. – 2012. – Vol. 129 (Suppl. 1). – S132–6.Наместников Ю. А. Диагностика гиперкоагуляции с помощью теста генерации тромбина // Автореферат диссертации на соискание ученой степени кандидата медицинских наук. – Санкт-Петербург. Февраль 2012 г.Наместников Ю. А. Диагностика гиперкоагуляции с помощью теста генерации тромбина // Автореферат диссертации на соискание ученой степени кандидата медицинских наук. – Санкт-Петербург. Февраль 2012 г.Guyatt G. H., Akl E. A., Crowther M. et al. Executive Summary: Antithrombotic Therapy and Prevention of Thrombosis. – 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines // Chest. – 2012. – 141. – 7S-47S.Guyatt G. H., Akl E. A., Crowther M. et al. Executive Summary: Antithrombotic Therapy and Prevention of Thrombosis. – 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines // Chest. – 2012. – 141. – 7S-47S.Kinasewitz G. Coagulopathy of the critically ill // XXIV ISTH Congress. Amsterdam, June 29 – July 4, 2013.Kinasewitz G. Coagulopathy of the critically ill // XXIV ISTH Congress. Amsterdam, June 29 – July 4, 2013.Johansson P. I., S rensen A.M et al. Disseminated intravascular coagulation or acute coagulopathy of trauma shock early after trauma? An observational study // Critical Care. – 2011. – Vol. 15. – R272 http://ccforum.com/content/15/6/R272.Johansson P. I., S rensen A.M et al. Disseminated intravascular coagulation or acute coagulopathy of trauma shock early after trauma? An observational study // Critical Care. – 2011. – Vol. 15. – R272 http://ccforum.com/content/15/6/R272.Marchal G., Leroux M. E., Samama M. – Atlas de Thrombodynamographie: Editeur SPEI. Paris, 1960.Marchal G., Leroux M. E., Samama M. – Atlas de Thrombodynamographie: Editeur SPEI. Paris, 1960.Spalding GJ, Hartrumpf M, Sierig T, et al. Cost reduction of perioperative coagulation management in cardiac surgery: value of bedside thrombelastography (ROTEM) // Eur J Cardiothorac Surg. – 2007. – Vol. 31. – P. 1052–1057.Spalding GJ, Hartrumpf M, Sierig T, et al. Cost reduction of perioperative coagulation management in cardiac surgery: value of bedside thrombelastography (ROTEM) // Eur J Cardiothorac Surg. – 2007. – Vol. 31. – P. 1052–1057.Bowbrick V. A., Mikhailidis D. P., Stansby G. Value of Thromboelastography in the Assessment of Platelet Function // Clin. Appl. Thromb. Hemos. – 2003.– Vol. 2. – P. 137–142.Bowbrick V. A., Mikhailidis D. P., Stansby G. Value of Thromboelastography in the Assessment of Platelet Function // Clin. Appl. Thromb. Hemos. – 2003.– Vol. 2. – P. 137–142.Hartet H. Blutgerinnungstdien mit der Thromboelastograhie, einem neun Untersuchingsverfahen // Klin Wochenscr. – 1948. – Vol. 26. – P. 577–583.Hartet H. Blutgerinnungstdien mit der Thromboelastograhie, einem neun Untersuchingsverfahen // Klin Wochenscr. – 1948. – Vol. 26. – P. 577–583.Hunt and B.J., Lyons G. Thromboelastography should be available in every labour ward // Int. J. Obst. Anesth.– 2005. Vol. 14.– P. 324–327.Hunt and B.J., Lyons G. Thromboelastography should be available in every labour ward // Int. J. Obst. Anesth.– 2005. Vol. 14.– P. 324–327.Salooja N., Perry D. J. Thrombelastography // Blood. Coagul. Fibrinolysis – 2001. – Vol. 12. – P. 327–337.Salooja N., Perry D. J. Thrombelastography // Blood. Coagul. Fibrinolysis – 2001. – Vol. 12. – P. 327–337.Kang Y. G. et al. Intraoperative changes in blood coagulation and thromboelastographic monitoring in liver transplantation // Anesth. Analg. – 1985. – Vol. 64. – P. 888–896.Kang Y. G. et al. Intraoperative changes in blood coagulation and thromboelastographic monitoring in liver transplantation // Anesth. Analg. – 1985. – Vol. 64. – P. 888–896.Wohlauer M. V., Moore E. E., Harr J. et al. A standardized technique for performing thromoelastography in rodents // SHOCK. – 2011. – Vol. 36 (5). – P. 524–526.Wohlauer M. V., Moore E. E., Harr J. et al. A standardized technique for performing thromoelastography in rodents // SHOCK. – 2011. – Vol. 36 (5). – P. 524–526.Kozek-Langenecker SA, Afshari A, Albaladejo P, et al. Management of severe operative bleeding: Guidelines from the European Society of Anesthesiology // EJA.– 2013.– Vol. 30 (6).– P.270–382.Kozek-Langenecker SA, Afshari A, Albaladejo P, et al. Management of severe operative bleeding: Guidelines from the European Society of Anesthesiology // EJA.– 2013.– Vol. 30 (6).– P.270–382.Schlimp C. J. Chances and problems of whole blood testing and other options to estimate functional fibrinogen and coagulopathy in practice // 22nd International Congress on Fibrinolysis and Proteolysis. Marseille, France. 6–9 July 2014. Book of abstracts. – IS13.Schlimp C. J. Chances and problems of whole blood testing and other options to estimate functional fibrinogen and coagulopathy in practice // 22nd International Congress on Fibrinolysis and Proteolysis. Marseille, France. 6–9 July 2014. Book of abstracts. – IS13.Samama S. M. Perioperative management of massive bleeding // 22nd International Congress on Fibrinolysis and Proteolysis. Marseille, France. 6–9 July 2014. Book of abstracts. – IS14.Samama S. M. Perioperative management of massive bleeding // 22nd International Congress on Fibrinolysis and Proteolysis. Marseille, France. 6–9 July 2014. Book of abstracts. – IS14.Sukhanov V., Petrova O.. Fibrinolysis and osmolar GAP in critically ill patients. // 22nd International Congress on Fibrinolysis and Proteolysis. Marseille, France. 6–9 July 2014. Book of abstracts. – P. 13.Sukhanov V., Petrova O.. Fibrinolysis and osmolar GAP in critically ill patients. // 22nd International Congress on Fibrinolysis and Proteolysis. Marseille, France. 6–9 July 2014. Book of abstracts. – P. 13.Gorlinger K., Dirkmann D., Solomon C. et al. Fast interpretation of thromboelastometry in non-cardiac surgery: reliability in patients with hypo-, normo-, and hypercoagulability // Br. J. Anaesth. – 2012. P. 1–9. doi:10.1093/bja/aes374 / http://bja.oxfordjournals.org/content/early/2012/10/30/bja. aes374.full.pdf+html /.Gorlinger K., Dirkmann D., Solomon C. et al. Fast interpretation of thromboelastometry in non-cardiac surgery: reliability in patients with hypo-, normo-, and hypercoagulability // Br. J. Anaesth. – 2012. P. 1–9. doi:10.1093/bja/aes374 / http://bja.oxfordjournals.org/content/early/2012/10/30/bja. aes374.full.pdf+html /.Tanakaa K. A., Badera S. O., Gorlingerb K. Novel approaches in management of perioperative coagulopathy // Curr. Opin. Anesthesiol. – 2014. – Vol. 27. – P. 1–9.Tanakaa K. A., Badera S. O., Gorlingerb K. Novel approaches in management of perioperative coagulopathy // Curr. Opin. Anesthesiol. – 2014. – Vol. 27. – P. 1–9.Weber C. F., Gorlinger K., Meininger D. et al. Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients. // Anesthesiology. – 2012. – Vol. 117. – P. 531–547.Weber C. F., Gorlinger K., Meininger D. et al. Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients. // Anesthesiology. – 2012. – Vol. 117. – P. 531–547.Lee J. W., Yoo Y. C., Park H. K. et al. Fresh frozen plasma in pump priming for congenital heart surgery: evaluation of effects on postoperative coagulation profiles using a fibrinogen assay and rotational thromboelastometry // Yonsei. Med. J. – 2013. Vol. 54. – P. 752–762.Lee J. W., Yoo Y. C., Park H. K. et al. Fresh frozen plasma in pump priming for congenital heart surgery: evaluation of effects on postoperative coagulation profiles using a fibrinogen assay and rotational thromboelastometry // Yonsei. Med. J. – 2013. Vol. 54. – P. 752–762.Dekker S. E., Viersen V. A., Duvekot A. et al. Lysis onset time as diagnostic rotational thromboelastometry parameter for fast detection of hyperfibrinolysis // Anesthesiology. – 2014. – Vol. 121 (1). – P. 89–97. doi: 10.1097/ALN.0000000000000229.Dekker S. E., Viersen V. A., Duvekot A. et al. Lysis onset time as diagnostic rotational thromboelastometry parameter for fast detection of hyperfibrinolysis // Anesthesiology. – 2014. – Vol. 121 (1). – P. 89–97. doi: 10.1097/ALN.0000000000000229.Ronald A. and Dunning J. Can the use of thromboelastography predict and decrease bleeding and blood and blood product requirements in adult patients undergoing cardiac surgery? // Interact. CardioVasc. Thorac. Surg. – 2005. Vol.4. – P.456–463; originally published online Jul 11, 2005. DOI: 10.1510/ icvts.2005.115154.Ronald A. and Dunning J. Can the use of thromboelastography predict and decrease bleeding and blood and blood product requirements in adult patients undergoing cardiac surgery? // Interact. CardioVasc. Thorac. Surg. – 2005. Vol.4. – P.456–463; originally published online Jul 11, 2005. DOI: 10.1510/ icvts.2005.115154.Gabrielli A. et al. Civetta, Taylor, and Kirby‘s Manual of Critical Care. – 2012 by LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER business.Gabrielli A. et al. Civetta, Taylor, and Kirby‘s Manual of Critical Care. – 2012 by LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER business.Суханов В. А. и Коряков И. О. Способ определения гиперкоагуляции крови // Лабораторное дело.– 1985. – N 12.– с. 722–724.Суханов В. А. и Коряков И. О. Способ определения гиперкоагуляции крови // Лабораторное дело.– 1985. – N 12.– с. 722–724.Spiezia L., Campello E., Rossetto V. et al. Hypofibrinolysis in patients with venous thromboembolism and cancer // Tromb. Res. – 2010. – Vol. 125. – P166–191.Spiezia L., Campello E., Rossetto V. et al. Hypofibrinolysis in patients with venous thromboembolism and cancer // Tromb. Res. – 2010. – Vol. 125. – P166–191.Перлик Э. Метод фибриновых пластинок по Аструпу и т. д. Антикоагулянты. – Медицина, Ленинградское отделение, 1965. – с.341–349.Перлик Э. Метод фибриновых пластинок по Аструпу и т. д. Антикоагулянты. – Медицина, Ленинградское отделение, 1965. – с.341–349.Перлик Э. Эуглобулиновый метод. Антикоагулянты. – Медицина, Ленинградское отделение, 1965. – с.341.Перлик Э. Эуглобулиновый метод. Антикоагулянты. – Медицина, Ленинградское отделение, 1965. – с.341.Spalding G. J. et al. Cost reduction of perioperative coagulation management in cardiac surgery: value of «bedside» thrombelastography (ROTEM) // Eur. J. Cardiothorac. Surg. – 2007. – Vol. 31. P. 1052–1057.Spalding G. J. et al. Cost reduction of perioperative coagulation management in cardiac surgery: value of «bedside» thrombelastography (ROTEM) // Eur. J. Cardiothorac. Surg. – 2007. – Vol. 31. P. 1052–1057.Kolde H. J. Haemostasis. Physiology, Pathology, Diagnostics. – Pentapharm Ltd., Basel/Switzerland, 2ndedition. – 2004. – P. 120–126.Kolde H. J. Haemostasis. Physiology, Pathology, Diagnostics. – Pentapharm Ltd., Basel/Switzerland, 2ndedition. – 2004. – P. 120–126.Sukhanov V. A., Bauman N. N., Levit A. L. Hyperfibrinolysis: its express diagnosis and role in the development of haemorrhagic syndrome after cardiopulmonary bypass // Cor. Vasa. – 1988. Vol. 30 (6). – P. 442–446.Sukhanov V. A., Bauman N. N., Levit A. L. Hyperfibrinolysis: its express diagnosis and role in the development of haemorrhagic syndrome after cardiopulmonary bypass // Cor. Vasa. – 1988. Vol. 30 (6). – P. 442–446.Sukhanov V. A. and Petrova O. Y. Application of thromboelastography parameters for the prediction of venous thromboembolism in cancer patient receiving chemotherapy // Thromb. Res.– 2014.– Vol. 133 (S.2).– PS 203.Sukhanov V. A. and Petrova O. Y. Application of thromboelastography parameters for the prediction of venous thromboembolism in cancer patient receiving chemotherapy // Thromb. Res.– 2014.– Vol. 133 (S.2).– PS 203.George D. J., Agnelli G., Fisher W. et al. Venous Thromboembolism Prevention with Semuloparin in Cancer Patients Initiating Chemotherapy: Benefit-Risk Assessment by VTE Risk in SAVE-ONCO // Blood. – 2011. – ASH Annual Meeting Program and Proceedings.George D. J., Agnelli G., Fisher W. et al. Venous Thromboembolism Prevention with Semuloparin in Cancer Patients Initiating Chemotherapy: Benefit-Risk Assessment by VTE Risk in SAVE-ONCO // Blood. – 2011. – ASH Annual Meeting Program and Proceedings.Streiff M. B., et al // NCCN Clinical Practice Guidelines on Venous Thromboembolic Disease. http://www.nccn. org/professionals/physician_gls/pdf/vte.pdf; 2013.Streiff M. B., et al // NCCN Clinical Practice Guidelines on Venous Thromboembolic Disease. http://www.nccn. org/professionals/physician_gls/pdf/vte.pdf; 2013.Mandala M., Falanga A., Roila F. Management of venous thromboembolism in cancer patients: ESMP Clinical Practice Guidelines // Ann. Oncol. – 2011. – Vol. 22. – Suppl 6: vi85–92.Mandala M., Falanga A., Roila F. Management of venous thromboembolism in cancer patients: ESMP Clinical Practice Guidelines // Ann. Oncol. – 2011. – Vol. 22. – Suppl 6: vi85–92.Пат. 2015515 Российская Федерация. Способ определения гиперкоагуляции крови / Суханов В. А., Коряков И. О., Амон Е. П.; заявитель Диагностический центр, патентообладатель Суханов В. А. заявл. 10.09.1991; опубл. 30.06.1994.Пат. 2015515 Российская Федерация. Способ определения гиперкоагуляции крови / Суханов В. А., Коряков И. О., Амон Е. П.; заявитель Диагностический центр, патентообладатель Суханов В. А. заявл. 10.09.1991; опубл. 30.06.1994.Пат. 2015515 Российская Федерация. Способ прогнозирования и диагностики гиперфибринолиза / Суханов В. А.; заявитель и патентообладатель Суханов В. А. заявл. 27.08.2007; опубл. 20.06.2009.Пат. 2015515 Российская Федерация. Способ прогнозирования и диагностики гиперфибринолиза / Суханов В. А.; заявитель и патентообладатель Суханов В. А. заявл. 27.08.2007; опубл. 20.06.2009.

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