Download PDF
Semin Thromb Hemost 2014; 40(03): 319-324
DOI: 10.1055/s-0034-1370770
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Risk Assessment for Thrombosis in Cancer

Marcelo Gomes
1   Section of Vascular Medicine, Sydell and Arnold Miller Family Heart & Vascular Institute, Cleveland Clinic Foundation, Cleveland, Ohio
,
Alok A. Khorana
2   Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, Ohio
› Author Affiliations
Further Information

Publication History

Publication Date:
05 March 2014 (online)

    Permissions and Reprints

Abstract

Patients with active malignancy are well-known to be at higher risk for venous thromboembolism (VTE). However, the risk of VTE varies considerably between patients and in the same patient over the natural history of their malignancy. Multiple clinical risk factors including primary site of cancer, use of systemic therapy including novel targeted agents, surgery, and hospitalization are known to increase the risk of VTE. Multiple candidate biomarkers including tissue factor, D-dimer, and soluble P-selectin have been identified. However, risk cannot be reliably predicted based on single risk factors or biomarkers. A risk assessment score has been validated in multiple populations and can identify patients at high risk for cancer-associated VTE. This review discusses the risk factors, predictive biomarkers, and new guidelines, which recommend risk assessment of VTE for all cancer patients. Potential applications of risk assessment, including targeted thromboprophylaxis, are also identified in this review.

Keywords

venous thromboembolism - risk score - risk factors - cancer
 

  • References

  • 1 Horsted F, West J, Grainge MJ. Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med 2012; 9 (7) e1001275
    CrossrefPubMedGoogle Scholar
  • 2 Moore 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; 29 (25) 3466-3473
    CrossrefPubMedGoogle Scholar
  • 3 Maraveyas A, Waters J, Roy R , et al. Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer. Eur J Cancer 2012; 48 (9) 1283-1292
    CrossrefPubMedGoogle Scholar
  • 4 Lyman GH, Khorana AA, Kuderer NM , et al; American Society of Clinical Oncology Clinical Practice. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013; 31 (17) 2189-2204
    CrossrefPubMedGoogle Scholar
  • 5 Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer 2007; 110 (10) 2339-2346
    CrossrefPubMedGoogle Scholar
  • 6 Samama MM. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study. Arch Intern Med 2000; 160 (22) 3415-3420
    CrossrefPubMedGoogle Scholar
  • 7 Königsbrügge O, Lötsch F, Reitter EM , et al. Presence of varicose veins in cancer patients increases the risk for occurrence of venous thromboembolism. J Thromb Haemost 2013; 11 (11) 1993-2000
    CrossrefPubMedGoogle Scholar
  • 8 Khorana AA, Connolly GC. Assessing risk of venous thromboembolism in the patient with cancer. J Clin Oncol 2009; 27 (29) 4839-4847
    CrossrefPubMedGoogle Scholar
  • 9 Wun T, White RH. Venous thromboembolism in patients with acute leukemia, lymphoma, and multiple myeloma. Thromb Res 2010; 125 (Suppl. 02) S96-S102
    CrossrefPubMedGoogle Scholar
  • 10 Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005; 293 (6) 715-722
    CrossrefPubMedGoogle Scholar
  • 11 Blom JW, Osanto S, Rosendaal FR. The risk of a venous thrombotic event in lung cancer patients: higher risk for adenocarcinoma than squamous cell carcinoma. J Thromb Haemost 2004; 2 (10) 1760-1765
    CrossrefPubMedGoogle Scholar
  • 12 Chew HK, Davies AM, Wun T, Harvey D, Zhou H, White RH. The incidence of venous thromboembolism among patients with primary lung cancer. J Thromb Haemost 2008; 6 (4) 601-608
    CrossrefPubMedGoogle Scholar
  • 13 Ahlbrecht J, Dickmann B, Ay C , et al. Tumor grade is associated with venous thromboembolism in patients with cancer: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol 2012; 30 (31) 3870-3875
    CrossrefPubMedGoogle Scholar
  • 14 Dickmann B, Ahlbrecht J, Ay C , et al. Regional lymph node metastases are a strong risk factor for venous thromboembolism: results from the Vienna Cancer and Thrombosis Study. Haematologica 2013; 98 (8) 1309-1314
    CrossrefPubMedGoogle Scholar
  • 15 Marras LC, Geerts WH, Perry JR. The risk of venous thromboembolism is increased throughout the course of malignant glioma: an evidence-based review. Cancer 2000; 89 (3) 640-646
    CrossrefPubMedGoogle Scholar
  • 16 Lee AY, Levine MN, Butler G , et al. Incidence, risk factors, and outcomes of catheter-related thrombosis in adult patients with cancer. J Clin Oncol 2006; 24 (9) 1404-1408
    CrossrefPubMedGoogle Scholar
  • 17 Chopra V, Anand S, Hickner A , et al. Risk of venous thromboembolism associated with peripherally inserted central catheters: a systematic review and meta-analysis. Lancet 2013; 382 (9889) 311-325
    CrossrefPubMedGoogle Scholar
  • 18 Elting LS, Escalante CP, Cooksley C , et al. Outcomes and cost of deep venous thrombosis among patients with cancer. Arch Intern Med 2004; 164 (15) 1653-1661
    CrossrefPubMedGoogle Scholar
  • 19 Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton III LJ. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160 (6) 809-815
    CrossrefPubMedGoogle Scholar
  • 20 Starling N, Rao S, Cunningham D , et al. Thromboembolism in patients with advanced gastroesophageal cancer treated with anthracycline, platinum, and fluoropyrimidine combination chemotherapy: a report from the UK National Cancer Research Institute Upper Gastrointestinal Clinical Studies Group. J Clin Oncol 2009; 27 (23) 3786-3793
    CrossrefPubMedGoogle Scholar
  • 21 Kabbinavar F, Hurwitz HI, Fehrenbacher L , et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003; 21 (1) 60-65
    CrossrefPubMedGoogle Scholar
  • 22 Nalluri SR, Chu D, Keresztes R, Zhu X, Wu S. Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 2008; 300 (19) 2277-2285
    CrossrefPubMedGoogle Scholar
  • 23 Hurwitz HI, Saltz LB, Van Cutsem E , et al. Venous thromboembolic events with chemotherapy plus bevacizumab: a pooled analysis of patients in randomized phase II and III studies. J Clin Oncol 2011; 29 (13) 1757-1764
    CrossrefPubMedGoogle Scholar
  • 24 Bennett CL, Schumock GT, Desai AA , et al. Thalidomide-associated deep vein thrombosis and pulmonary embolism. Am J Med 2002; 113 (7) 603-606
    CrossrefPubMedGoogle Scholar
  • 25 Cavo M, Zamagni E, Cellini C , et al. Deep-vein thrombosis in patients with multiple myeloma receiving first-line thalidomide-dexamethasone therapy. Blood 2002; 100 (6) 2272-2273
    CrossrefPubMedGoogle Scholar
  • 26 Petrelli F, Borgonovo K, Cabiddu M, Ghilardi M, Barni S. Risk of anti-EGFR monoclonal antibody-related hypomagnesemia: systematic review and pooled analysis of randomized studies. Expert Opin Drug Saf 2012; 11 (Suppl. 01) S9-S19
    CrossrefPubMedGoogle Scholar
  • 27 Trujillo-Santos J, Di Micco P, Iannuzzo M , et al; RIETE Investigators. Elevated white blood cell count and outcome in cancer patients with venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost 2008; 100 (5) 905-911
    PubMedGoogle Scholar
  • 28 Trujillo-Santos J, Nieto JA, Tiberio G , et al; RIETE Registry. Predicting recurrences or major bleeding in cancer patients with venous thromboembolism. Findings from the RIETE Registry. Thromb Haemost 2008; 100 (3) 435-439
    PubMedGoogle Scholar
  • 29 Louzada ML, Majeed H, Dao V, Wells PS. Risk of recurrent venous thromboembolism according to malignancy characteristics in patients with cancer-associated thrombosis: a systematic review of observational and intervention studies. Blood Coagul Fibrinolysis 2011; 22 (2) 86-91
    CrossrefPubMedGoogle Scholar
  • 30 Hutten BA, Prins MH, Gent M, Ginsberg J, Tijssen JG, Büller HR. Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J Clin Oncol 2000; 18 (17) 3078-3083
    CrossrefPubMedGoogle Scholar
  • 31 Louzada ML, Carrier M, Lazo-Langner A , et al. Development of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism. Circulation 2012; 126 (4) 448-454
    CrossrefPubMedGoogle Scholar
  • 32 Pabinger I, Thaler J, Ay C. Biomarkers for prediction of venous thromboembolism in cancer. Blood 2013; 122 (12) 2011-2018
    CrossrefPubMedGoogle Scholar
  • 33 Bharthuar A, Khorana AA, Hutson A , et al. Circulating microparticle tissue factor, thromboembolism and survival in pancreaticobiliary cancers. Thromb Res 2013; 132 (2) 180-184
    CrossrefPubMedGoogle Scholar
  • 34 Thaler J, Ay C, Mackman N , et al. Microparticle-associated tissue factor activity, venous thromboembolism and mortality in pancreatic, gastric, colorectal and brain cancer patients. J Thromb Haemost 2012; 10 (7) 1363-1370
    CrossrefPubMedGoogle Scholar
  • 35 Agnelli G, Gussoni G, Bianchini C , et al; PROTECHT Investigators. Nadroparin for the prevention of thromboembolic events in ambulatory patients with metastatic or locally advanced solid cancer receiving chemotherapy: a randomised, placebo-controlled, double-blind study. Lancet Oncol 2009; 10 (10) 943-949
    CrossrefPubMedGoogle Scholar
  • 36 Agnelli G, George DJ, Kakkar AK , et al; SAVE-ONCO Investigators. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Engl J Med 2012; 366 (7) 601-609
    CrossrefPubMedGoogle Scholar
  • 37 Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111 (10) 4902-4907
    CrossrefPubMedGoogle Scholar
  • 38 Ay C, Dunkler D, Marosi C , et al. Prediction of venous thromboembolism in cancer patients. Blood 2010; 116 (24) 5377-5382
    CrossrefPubMedGoogle Scholar
  • 39 Khorana AA. Cancer and coagulation. Am J Hematol 2012; 87 (Suppl. 01) S82-S87
    CrossrefPubMedGoogle Scholar
  • 40 Streiff MB, Bockenstedt PL, Cataland SR , et al. Venous thromboembolic disease. J Natl Compr Canc Netw 2013; 11: 1402-1429
    CrossrefPubMedGoogle Scholar
  • 41 Mandalà M, Falanga A, Roila F ; ESMO Guidelines Working Group. Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol 2011; 22 (Suppl. 06) vi85-vi92
    CrossrefPubMedGoogle Scholar
  • 42 Palumbo A, Rajkumar SV, Dimopoulos MA , et al; International Myeloma Working Group. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia 2008; 22 (2) 414-423
    CrossrefPubMedGoogle Scholar
  • 43 Sousou T, Khorana AA. Cancer patients and awareness of venous thromboembolism. Cancer Invest 2010; 28 (1) 44-45
    CrossrefPubMedGoogle Scholar
  • 44 Verso M, Agnelli G, Barni S, Gasparini G, LaBianca R. A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the Protecht score. Intern Emerg Med 2012; 7 (3) 291-292
    PubMedGoogle Scholar
  • 45 George D, Agnelli G, Fisher W , et al. Venous thromboembolism (VTE) prevention with semuloparin in cancer patients initiating chemotherapy: benefit-risk assessment by VTE risk in SAVE-ONCO. Blood (ASH Annual Meeting Program and Proceedings) 2011; 118 : Abstract 206
    PubMedGoogle Scholar
  • 46 Stender MT, Frøkjaer JB, Larsen TB, Lundbye-Christensen S, Thorlacius-Ussing O. Preoperative plasma D-dimer is a predictor of postoperative deep venous thrombosis in colorectal cancer patients: a clinical, prospective cohort study with one-year follow-up. Dis Colon Rectum 2009; 52 (3) 446-451
    CrossrefPubMedGoogle Scholar
  • 47 Ay C, Vormittag R, Dunkler D , et al. D-dimer and prothrombin fragment 1 + 2 predict venous thromboembolism in patients with cancer: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol 2009; 27 (25) 4124-4129
    CrossrefPubMedGoogle Scholar
  • 48 Ay C, Dunkler D, Simanek R , et al. Prediction of venous thromboembolism in patients with cancer by measuring thrombin generation: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol 2011; 29 (15) 2099-2103
    CrossrefPubMedGoogle Scholar
  • 49 Khorana AA, Ahrendt SA, Ryan CK , et al. Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer. Clin Cancer Res 2007; 13 (10) 2870-2875
    CrossrefPubMedGoogle Scholar
  • 50 Khorana AA, Francis CW, Menzies KE , et al. Plasma tissue factor may be predictive of venous thromboembolism in pancreatic cancer. J Thromb Haemost 2008; 6 (11) 1983-1985
    CrossrefPubMedGoogle Scholar
  • 51 Zwicker JI, Liebman HA, Neuberg D , et al. Tumor-derived tissue factor-bearing microparticles are associated with venous thromboembolic events in malignancy. Clin Cancer Res 2009; 15 (22) 6830-6840
    CrossrefPubMedGoogle Scholar
  • 52 Ay C, Simanek R, Vormittag R , et al. High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). Blood 2008; 112 (7) 2703-2708
    CrossrefPubMedGoogle Scholar
  • 53 Vormittag R, Simanek R, Ay C , et al. High factor VIII levels independently predict venous thromboembolism in cancer patients: the cancer and thrombosis study. Arterioscler Thromb Vasc Biol 2009; 29 (12) 2176-2181
    CrossrefPubMedGoogle Scholar