Thromb Haemost 2002; 87(04): 575-579
DOI: 10.1055/s-0037-1613051
Review Article
Schattauer GmbH

Venous Thrombosis in Patients with Solid Tumors: Determination of Frequency and Characteristics

Sabah Sallah
1   Division of Hematology/Oncology, University of Tennessee Health Science Center, Memphis, Tennessee
,
Jim Y. Wan
2   Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
,
Nam P. Nguyen
3   Department of Radiation Oncology, Southwestern University, Dallas, Texas
› Author Affiliations
Further Information

Publication History

Received 02 August 2001

Accepted after resubmission 08 January 2002

Publication Date:
08 December 2017 (online)

Summary

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are well recognized complications of cancer. However, our current knowledge of this association is derived from studies conducted more than a decade ago. In light of the changes in medical practice and the improvement in cancer care in recent years, a re-evaluation of the relationship between malignancy and venous thrombosis is in order. Of a total of 1041 patients with solid tumors admitted to 3 major medical centers, there were 81 (7.8%) diagnosed with DVT/PE. Patients were more likely to develop DVT/PE during chemotherapy (p = .0001). Advanced malignancies (p = .001), renal carcinoma (p = .005), pancreatic (p = .001), gastric (p = .014) and brain tumors (p = .001) were independent variables strongly associated with the occurrence of venous thrombosis. The occurrence of thrombotic events in the population tested in this study did not adversely affect survival (p = .082).

The study identifies subset of patients with cancer at high risk for venous thrombosis. Early prophylaxis with anticoagulants in these patients may be warranted. Most importantly, further clinical trials are desperately awaited to detect possible new trends in the frequency and types of thrombotic events and to better define prevention strategies in cancer patients at risk for thrombosis.

The association between venous thromboembolic disease (VTD) and malignant neoplastic disorders is well known and has been the subject of several reports for more than a century (1–8). There is a general agreement among investigators that thrombotic complications in patients with cancer occur at a rather high frequency, and that other circumstantial factors such as surgery or chemotherapy potentiates this risk (9,10). However, several important considerations pertaining to cancer and thrombosis continue to be shrouded in controversy. For example, there are inexplicable differences in the proportion of patients with cancer diagnosed with deep venous thrombosis (DVT) or pulmonary embolism (PE) reported in the literature (2, 4, 5, 11). In the absence of large well-controlled studies, one may only postulate on the reasons that contributed to these differences. The inclusion of different types of VTD such as superficial, venous, arterial or vascular access device-induced thrombosis may have led to overestimation of the incidence of these events in patients with underlying malignancy. Another possible explanation for this discrepancy relates to the use of a variety of diagnostic and methodological criteria ranging from observation and clinical suspicion to more invasive procedures resulting in considerable differences in the rate of reported clotting events (12). Along the same line of discussion, one may argue whether VTD is a random event or constitutes a complication that occurs more commonly in patients with distinct characteristics and certain tumor types. To further investigate the association between malignancy and thrombosis, we evaluated 1041 patients with solid tumors for the risk of DVT/PE. The main objectives of the study were to determine the frequency of DVT/PE based on validated diagnostic criteria and to identify patients with cancer at high risk for developing these thrombotic episodes. Also, we evaluated the impact of VTD on the survival of these patients.

 
  • References

  • 1 Trousseau A. Phlegmasia alba dolens. In: Clinique Medicale de L’Hotel-Dieu de Paris. London: New Sydenham Society; 1865
  • 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: 566-85.
  • 3 Miller SP, Sanchez AJ, Stefanski T, Zuckerman L. Coagulation disorders in cancer: clinical and laboratory studies. Cancer 1976; 20: 1452-65.
  • 4 Donati MB, Poggi A. Malignancy and haemostasis. Br J Haematol 1983; 44: 173-182.
  • 5 Piccioli A, Prandoni P, Ewenstein BM, Goldhaber SZ. Cancer and venous thromboembolism. Am Heart J 1996; 132: 850-5.
  • 6 Johnson MJ, Walker ID, Sproule MW, Conkie J. Abnormal coagulation and deep venous thrombosis in patients with advanced cancer. Clin Lab Haematol 1999; 21: 51-4.
  • 7 Francis JL, Biggerstaff J, Amirkkosravia A. Hemostasis and malignancy. Semin Thromb Hemost 1998; 24: 93-109.
  • 8 Monreal M, Salvador R, Soriano V, Sabrina M. Cancer and deep venous thrombosis. Arch Intern Med 1988; 148: 485.
  • 9 Goodnough LT, Saito H, Manni A, Jones PK, Pearson OH. Increased incidence of thromboembolism in stage IV breast cancer patients treated with a five-drug chemotherapy regimen: a study of 159 patients. Cancer 1984; 54: 1264-8.
  • 10 Levine MN, Cent M, Hirsh J, Arnold A, Goodyear MD, Hryniuk W. et al. The thrombogenic effect of anticancer drug therapy in women with stage II breast cancer. N Engl J Med 1988; 318: 404-7.
  • 11 Naschitz JE, Yeshurun D, Lev LM. Thromboembolism in cancer: changing trends. Cancer 1993; 71: 1384-90.
  • 12 Scates SM. Diagnosis and treatment of cancer-related thrombosis. Semin Thromb Hemost 1992; 18: 373-9.
  • 13 Sallah S, Wan JY, Nguyen NP, Hanrahan LR, Sigounas G. Disseminated intravascular coagulation in solid tumors: clinical and pathologic study. Thromb Haemost 2001; 86: 828-33.
  • 14 Sallah S, Wan JY. Inhibitors against factor VIII in patients with cancer: analysis of 41 patients. Cancer 2001; 91: 1067-74.
  • 15 Coleman RW, Rubin RN. Disseminated intravascular coagulation due to malignancy. Semin Oncol 1990; 17: 172-86.
  • 16 Donati MB. Cancer and Thrombosis: from phlegmasia alba dolens to transgenic mice. Thromb Haemost 1995; 74: 278-81.
  • 17 Luzzato G, Schafer AL. The prethrombotic state in cancer. Semin Oncol 1990; 17: 147-59.
  • 18 Durica SS. Venous thromboembolism in cancer patients. Curr Opin Hematol 1997; 04: 306-11.
  • 19 White RH, Zhou H, Romano PS. Length of hospital stay for treatment of deep venous thrombosis and the incidence of recurrent thromboembolism. Arch Intern Med 1998; 158: 1005-10.
  • 20 Wagner JR, Merino MJ, Pass HI, Linehan WM, Walther MM. Pulmonary infarcts can mimic pulmonary metastasis from renal cancer. J Urol 1997; 138: 1688-90.
  • 21 Friedell ML, Sujka SK, Welch JL, Simmons GT. Massive pulmonary embolus after surgery for renal carcinoma extending into inferior vena cava. Am Surg 1997; 63: 516-8.
  • 22 Babu SC, Mianoni T, Shah PM, Goyal A, Choudhury M, Eshghi M, Moggi RA, Sarabu MR, Lafaro RJ. Malignant renal tumor with extension to the inferior vena cava. Am J Surg 1998; 176: 137-9.
  • 23 Falanga A, Gordon GA. Isolation and characterization of cancer procoagulant: a cysteine proteinase from malignant tissue. Biochemistry 1985; 24: 5558-67.
  • 24 Kuzel T, Esparaz B, Green D, Kies M. Thrombogenicity of intrvenous 5-fluorouracil alone or in combination with cisplatin. Cancer 1990; 65: 885-9.
  • 25 Hotton RM, Khorsand M, Hank JA, Albertini M, Kim KM, Wilding G, Salamat MS, Larson MS, Larson M, Sondel P, Schiller JH. A phase Ib/II trial of granulocyte –macrophage-colony stimulating factor and interleukin-2 for renal cell carcinoma patients with pulmonary metastasis: a case of fatal central nervous system thrombosis. Cancer 2000; 88: 1892-901.
  • 26 Di Carlo V, Angelli G, Prandoni P, Coccheri S, Gensini GF, Gianese F, Mannucci MP. Dermatan sulphate for the prevention of postoperative venous thromboembolism in patients with cancer. DOS (Dermantan sulphate in Oncologic Surgery) study group. Thromb Haemost 1999; 82: 30-4.
  • 27 Somrenburg SK, Hettiarachchi RJK, Vink R, Buller HR. The effects of unfractionated heparin on survival in patients with malignancy: a systematic review. Thromb Haemost 1999; 82: 1600-4.
  • 28 Hettiarachchi RJK, Smorensburg SM, Ginsberg J, Levine M, Prins MH, Buller HR. Do heparins do more than just treat thrombosis? The influence of heparins on cancer spread. Thromb Haemost 1999; 82: 947-52.