Trousseau’s syndrome: The forgotten past or actual present?

Vorobyev A.V., Makatsaria A.D., Brenner B.

Department of Obstetrics and Gynecology, Faculty of Medical Prevention, I.M. Sechenov First Moscow State Medical University, Moscow 109004, Zemlyanoi Val str. 62, bld. 1, Russia
Objective. To carry out a systematic analysis of the data available in the current literature on the modern view on Trousseau’s syndrome
Material and methods. The review included the data of foreign and Russian articles published in the past 10 years and found in e-Library and PubMed on this topic.
Results. This paper provides a pathogenetic explanation for the increased thrombotic potential in cancer patients, which underlies tumor growth and metastasis. In addition to direct thrombotic events, the paper also describes hemorrhagic complications resulting from systemic coagulopathy, including disseminated intravascular coagulation, hemolytic thrombotic microangiopathy, and excessive fibrinolysis.
Conclusion. At present, any manifestation of thrombohemorrhagic complications in patients with malignant tumors can be classified as a paraneoplastic syndrome (Trousseau’s syndrome). In addition to Virchow’s classic triad, hyperproduction of tissue factor (TF), the main initiator of the extrinsic coagulation pathway, underlies the pathophysiology of Trousseau’s syndrome. At the same time, the substantial release of microparticles from TF-bearing tumor cells is critical not only for clot formation, but also for the progression of tumor growth.


Trousseau’s syndrome
malignant neoplasms of female genital organs and breast
thrombotic events
hemostatic system
tumor metastasis
disseminated intravascular coagulation syndrome
pathogenesis of thrombotic events
cancer patients
prevention of thrombosis
hemostatic disorders

Supplementary Materials

  1. Table 1. Markers of the hemostasis system activation
  2. Table 2. The role of hemostasis system in the process of growth and progression of malignant neoplasm
  3. Figure 1. Modification of the Virchow’s triad
  4. Figure 2. Common pathogenesis of tumor growth and thrombotic complications


1. Trousseau A. Phlegmasia alba dolens. Clinique Medicale de l’Hotel-Dieu de Paris. 1865; 3: 654-712.

2. Chaturvedi S., Sidana S., Elson R., Khorana A.A., McCrae K.R. Symptomatic and incidental venous thromboembolic disease are both associated with mortality in patients with prostate cancer. PLoS One. 2014; 9: e94048.

3. Dammacco F., Vacca A., Procaccio P., Ria R., Marech I., Racanelli V. Cancer-related coagulopathy (Trousseau’s syndrome): review of the literature and experience of a single center of internal medicine. Clin. Exp. Med. 2013; 13(2): 85-97.

4. Langer F., Bokemeyer C. Crosstalk between cancer and haemostasis. Implications for cancer biologyand cancer-associated thrombosis with focus on tissue factor. Hamostaseologie. 2012; 32: 95-104.

5. Varki A. Trousseaus syndrome: multiple definitions and multiple mechanisms. Blood. 2007; 110(6): 1723-9.

6. Воробьев А.В. Состояние тромбоцитарного звена гемостаза у онкогинекологических больных. В кн.: Материалы VI Российского форума «Мать и дитя». Москва, октябрь 2004 г. М.; 2004: 318-9. [Vorobiev A.V. The state of platelet hemostasis in oncogynecologic patients. In: Materials of the VI Russian Forum “Mother and Child”. Moscow, October 2004; 2004: 318-9. (in Russian)]

7. Цыб А.Ф., Сушкевич Г.Н., Балуда М.В., Воробьев А.В., Чабров А.М. Принципы профилактики тромботических осложнений у онкологических больных (солидные образования). Пособие для врачей. Обнинск; 2008. 42с. [Tsyb A.F., Sushkevich G.N., Baluda M.V., Vorobyev A.V., Chabrov A.M. Principles of thrombotic complications prevention in cancer patients (solid formations). A manual for doctors. Obninsk; 2008. 42p. (in Russian)]

8. Khorana AA. Risk assessment for cancer-associated thrombosis: what is the best approach? Thromb. Res. 2012; 129(Suppl. 1): S10-5.

9. Макацария А.Д., Воробьев А.В., Бицадзе В.О. Злокачественные новообразования, тромбофилия, тромбозы. Монография. М.: Триада-Х; 2008. 650с. [Makatsariya A.D., Vorobyev A.V., Bitsadze V.O. Malignant neoplasms, thrombophilia, thromboses. Monograph. Moscow: Triada-X; 2008. 650p. (in Russian)]

10. Российские клинические рекомендации по диагностике, лечению и профилактике венозных тромбоэмболических осложнений. Ассоциация флебологов России, Всероссийское общество хирургов. М.: Медиа Сфера; 2010. [Russian clinical guidelines for the diagnosis, treatment and prevention of venous thromboembolic complications. Association of phlebologists of Russia, All-Russian Society of Surgeons. Moscow: Media Sphere; 2010. (in Russian)]

11. Hernández C., Orbe J., Roncal C., Alvarez-Hernandez M., Martinez de Lizarrondo S., Alves M.T. et al. Tissue factor expressed by microparticles is associated with mortality but not with thrombosis in cancer patients. Thromb. Haemost. 2013; 110(3): 598-608.

12. Hyman D.M., Soff G.A., Kampel L.J. Disseminated intravascular coagulation with excessive fibrinolysis in prostate cancer: a case series and review of the literature. Oncology. 2011; 81(2): 119-25.

13. Van Doormaal F.F., Terpstra W., Van Der Griend R., Prins M.H., Nijziel M.R., Van De Ree M.A. et al. Is extensive screening for cancer in idiopathic venous thromboembolism warranted? J. Thromb. Haemost. 2011; 9(1): 79-84.

14. Vorobiev A.V., Makatsaria A.D., Chabrov A.M. Thrombophilia markers in cancer patients during chemotherapy and radiation therapy. Pathophysiol. Haemost. Thromb. 2006; 35(1-2): A20.

15. Kitchens C.S. The contact system. Arch. Pathol. Lab. Med. 2002; 126(11):1382-6.

16. Bharthuar A., Khorana A.A., Hutson A., Wang J.G., Key N.S., Mackman N., Iyer R.V. Circulating microparticle tissue factor, thromboembolism and survival in pancreaticobiliary cancers. Thromb. Res. 2013; 132(2): 180-4.

17. Davila M., Robles-Carrillo L., Unruh D., Huo Q., Gardiner C., Sargent I.L. et al. Microparticle association and heterogeneity of tumor-derived tissue factor in plasma: is it important for coagulation activation? J. Thromb. Haemost. 2014; 12(2): 186-96.

18. Demers M., Wagner D.D. NETosis: a new factor in tumor progression and cancer-associated thrombosis. Semin. Thromb. Hemost. 2014; 40(3):277-83.

19. Thaler J., Ay C., Mackman N., Metz-Schimmerl S., Stift J., Kaider A. et al. Microparticle-associated tissue factor activity in patients with pancreatic cancer: correlation with clinicopathological features. Eur. J. Clin. Invest. 2013; 43(3): 277-85.

20. Geddings J.E., Mackman N. Tumor-derived tissue factor-positive microparticles and venous thrombosis in cancer patients. Blood. 2013; 122(11):1873-80.

21. Kocatürk B., Versteeg H.H. Tissue factor isoforms in cancer and coagulation: may the best isoform win. Thromb. Res. 2012; 129(Suppl. 1): S69-75.

22. Mackman N. New insights into the mechanisms of venous thrombosis. J. Clin. Invest. 2012; 122(7): 2331-6.

23. Rak J., Yu J.L., Luyendyk J., Mackman N. Oncogenes, Trousseau syndrome, and cancer-related changes in the coagulome of mice and humans. Cancer Res. 2006; 66(22): 10643-6.

24. Claussen C., Rausch A.V., Spath B. et al. Clinical significance of hemostatic activation markers in women with suspected ovarian cancer. Oncol. Res. Treat. 2014; 37: V669.

25. Fuchs T.A., Brill A., Wagner D.D. Neutrophil extracellular trap (NET) impact on deep vein thrombosis. Arterioscler. Thromb. Vasc. Biol. 2012; 32(8):1777-83.

26. Thaler J., Preusser M., Ay C., Kaider A., Marosi C., Zielinski C. et al. Intratumoral tissue factor expression and risk of venous thromboembolism in brain tumor patients. Thromb. Res. 2013; 131(2): 162-5.

27. Lo L., Valentine H., Harrison J., Hayes S., Welch I., Pritchard S. et al. Tissue factor expression in the metaplasia-adenoma-carcinoma sequence of gastric cancer in a European population. Br. J. Cancer. 2012; 107(7): 1125-30.

Received 18.04.2017

Accepted 28.04.2017

About the Authors

Vorobyov Alexander Viktorovich, Candidate of Medical Sciences, Associate Professor of the Department of Obstetrics and Gynecology of the Faculty
of Medical Prevention, I.M. Sechenov First Moscow State Medical University.
109004, Russia, Moscow, Zemlyanoi Val str. 62, bld. 1. Tel.: +79031056365. E-mail:
Makatsariya Alexander Davidovich, Corresponding Member of the Russian Academy of Sciences, Professor, Doctor of Medical Sciences,
Head of the Department of Obstetrics and Gynecology of the Faculty of Medical Prevention, I.M. Sechenov First Moscow State Medical University.
109004, Russia, Moscow, Zemlyanoi Val str. 62, bld. 1. Tel.: +79037280897. E-mail:
Brenner Benjamin, Professor, Director, Institute of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa,
Israel. E-mail:

For citations: Vorobyev A.V., Makatsaria A.D., Brenner B. Trousseau’s syndrome: The forgotten past or actual present? Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; (2): 27-34. (in Russian)

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