Since Trousseau’s time numerous studies have addressed the relationship between cancer and venous thromboembolism (VTE) providing firm evidence of the increased risk of subsequent clinically overt malignancy during the follow-up of patients with idiopathic VTE. These malignancies are not limited to certain subtypes, but involve virtually all body systems. This knowledge has led to a long-standing debate on the need to screen for occult malignancies patients with idiopathic VTE with no clinical evidence of cancer at the time of the index thrombotic event. In fact the high incidence of newly discovered cancers does not automatically imply that screening is indicated in these patients since it is unknown whether a substantial proportion of cancers can be diagnosed, whether the diagnosed cancers are treatable and what the impact on cancer-related mortality is. Proper clinical trials are being conducted to find an answer to these questions.

1.
Trousseau A: Phlegmasia alba dolens; in Clinique médicale de l’Hôtel-Dieu de Paris, ed 2. Paris, Baillière, 1865, vol 3, pp 659–712.
2.
Sproul EE: Carcinoma and venous thrombosis: The frequency of association of carcinoma in the body or tail of the pancreas with multiple venous thrombosis. Am J Cancer 1938;34:566–585.
3.
Ambrus JL, Ambrus CM, Mink IB, Pickern JW: Causes of death in cancer patients. J Med 1975;6:61–64.
4.
Kakkar VV, Howe CT, Nicolaides AN, Renney JTG, Clarke MB: Deep vein thrombosis of the leg. Is there a high-risk group? Am J Surg 1970;120:527–530.
5.
Hills NH, Pflugg JJ, Jeyasingh K, Boardman L, Calnam JS: Prevention of deep vein thrombosis by intermittent pneumatic compression of the calf. Br Med J 1972;1:131–135.
6.
Walsh JJ, Bonnar J, Wright FW: A study of pulmonary embolism and deep vein thrombosis after major gynaecological surgery using labelled fibrinogen phlebography and lung scanning. J Obstet Gynaecol Br Commonw 1974;81:311–316.
7.
Rosenberg IL, Evans M, Pollock AV: Prophylaxis of postoperative leg vein thrombosis by low dose subcutaneous heparin or peroperative calf muscle stimulation: A controlled clinical trial. Br Med J 1975;i:649–651.
8.
Sue-Ling HM, Johnston D, McMahon MV, Philips PR, Davies JA: Preoperative identification of patients at high risk of deep vein thrombosis after elective major abdominal surgery. Lancet 1986;i:1173–1176.
9.
Allan A, William JT, Bolton JP, LeQuesne LP: The use of graduated compression stockings in the prevention of postoperative deep vein thrombosis. Br J Surg 1983;70:172–174.
10.
Gore JM, Appelbaum JS, Greene HL, Dexter L, Dalen JE: Occult cancer in patients with acute pulmonary embolism. Ann Intern Med 1982;96:556–560.
11.
Aderka D, Brown A, Zelikovski A, Pinkhas J: Idiopathic deep vein thrombosis in an apparently healthy patient as a premonitory sign of occult cancer. Cancer 1986;57:1846–1849.
12.
Griffin MR, Stanson AS, Brown ML, et al: Deep venous thrombosis and pulmonary embolism. Risk of subsequent malignant neoplasms. Arch Intern Med 1987;147:1907–1911.
13.
Goldberg RJ, Seneff M, Gore JM, et al: Occult malignant neoplasms in patients with deep venous thrombosis. Arch Intern Med 1987;147:251–253.
14.
Monreal M, Salvador R, Soriano V, Sabria M: Cancer and deep venous thrombosis. Arch Intern Med 1988;148:485.
15.
Monreal M, Lafoz E, Casals A, et al: Occult cancer in patients with deep venous thrombosis. A systematic approach. Cancer 1991;67:541–545.
16.
Prandoni P, Lensing AWA, Buller H, Cogo A, Prins MH, Cattelan AM, et al: Deep vein thrombosis and the incidence of subsequent symptomatic cancer. N Engl J Med 1992;327:1128–1133.
17.
Ahmed Z, Mohyuddin Z: Deep vein thrombosis as a predictor of cancer. Angiology 1996;47:261–265.
18.
Bastounis EA, Karayannakis AJ, Makri GG, Alexiou D, Papalambros EL: The incidence of occult cancer in patients with deep vein thrombosis: A prospective study. J Intern Med 1996;239:153–156.
19.
Ranft J, Heidrick H: Frequency of malignant diseases in deep vein thrombosis of lower extremity. Int Angiol 1991;10:66–68.
20.
Nordstrom M, Lindblad B, Anderson H, Bergquist D, Kjellstrom T: Deep venous thrombosis and occult malignancy: An epidemiological study. BMJ 1994;308:891–894.
21.
Cornuz J, Pearson SD, Creager MA, Cook FF, Goldman L: Importance of findings of the initial evaluation for cancer in patients with symptomatic idiopathic deep venous thrombosis. Ann Intern Med 1996;125:785–793.
22.
Monreal M, Casals A, Boix J, et al: Occult cancer in patients with acute pulmonary embolism. A prospective study. Chest 1993;103:816–819.
23.
Monreal M, Fernandez-Liamazares J, Perandreu J, et al: Occult cancer in patients with venous thromboembolism: Which patients, which cancers. Thromb Haemost 1997;78:1316–1318.
24.
Hettiarachchi RJK, Lok J, Prins MH, et al: Undiagnosed malignancy in patients with deep-vein thrombosis. Incidence, risk indicators and diagnosis. Cancer 1998;83:100–105.
25.
Achkar A, Laaban JP, Horellou MH, et al: Prospective screening for occult cancer in patients with venous thromboembolism. Thromb Haemost 1997;(suppl):OC-1564.
26.
Rance A, Emmerich J, Guedj C, Fiessinger JN, et al: Occult cancer in patients with bilateral deep vein thrombosis. Lancet 1997;350:1448–1449.
27.
Rajan R, Levine M, Gent M, et al: The occurrence of subsequent malignancy in patients presenting with deep vein thrombosis: Results from a historical cohort study. Thromb Haemost 1998;79:19–22.
28.
Sorensen H, Mellemakjaer L, Steffensen FH, Olsen JH, Nielsen GL: The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism. N Engl J Med 1998;338:1169–1173.
29.
Baron JA, Gridley G, Weiderpass E, Nyren O, Linet M: Venous thromboembolism and cancer. Lancet 1998;351:1077–1080.
30.
Edwards RL, Morgan DL, Rickles FR: Animal tumor procoagulants: Registry of the Subcommittee on Haemostasis and Malignancy of the Scientific and Standardization Committee, International Society of Thrombosis and Haemostasis. Thromb Haemost 1990;63:133–138.
31.
Kubota T, Andoh K, Sekakata H, Tanaka H, Kobayashi N: Tissue factor released from leukemic cells. Thromb Haemost 1991;65:59–63.
32.
Francis JL: Haemostasis and cancer. Med Lab Sci 1989;46:331–346.
33.
Falanga A, Alessio MG, Donati MB, Barbui T: A new procoagulant in acute leukemia. Blood 1988;71:870–875.
34.
Gordon SG, Benson B: Analysis of serum cancer procoagulant activity and its possible use as a tumor marker. Thromb Res 1989;56:431–440.
35.
Lando PA, Edgington TS: An innate host response to the neoplastic cell: Syngeneic rat tumor cells can elicit a rapid de novo lymphoid procoagulant response. J Immunol 1985;135:3587–3595.
36.
Miyauchi S, Moroyama T, Kyoizumi S, et al: Malignant tumor cell lines produce interleukin-1-like factor. In Vitro Cell Dev Biol 1988;24:753–758.
37.
Noguchi M, Sakai T, Kisiel W: Identification and partial purification of a novel tumor-derived protein that induces tissue factor on cultured human endothelial cells. Biochem Biophys Res Commun 1989;160:222–227.
38.
Piccioli A, Prandoni P, Ewenstein BM, Goldhaber SZ: Cancer and venous thromboembolism. Am Heart J 1996;132:850–855.
39.
Dvorak HF: Abnormalities of hemostasis in malignant disease; in Colman EW, Hirsh J, Marder VJ, Salzman EW (eds): Haemostasis and Thrombosis: Basic Principles and Clinical Practice. Philadelphia, Lippincott, 1993, pp 1238–1254.
40.
Salzman EX, Hirsh J: The epidemiology, pathogenesis, and natural history of venous thrombosis; in Colman EW, Hirsh J, Marder VJ, Salzman EW (eds): Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Philadelphia, Lippincott, 1993, pp 1275–1296.
41.
Prandoni P, Piccioli A, Girolami A: Cancer and venous thromboembolism: An overview. Haematologica 1999;84:437–445.
42.
Prandoni P, Lensing AWA, Piccioli A, Bagatella P, Girolami A: Ultrasonography of contralateral veins in patients with unilateral deep-vein thrombosis. Lancet 1998;352:786.
43.
Piccioli A, Lensing AWA, Prandoni P: Screening for occult malignancy in patients with idiopathic venous thromboembolism (SOMIT). Study design. Thromb Haemost 1997(suppl):PS-489.
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