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
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
05. März 2014 (online)

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.

 
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 8 Khorana AA, Connolly GC. Assessing risk of venous thromboembolism in the patient with cancer. J Clin Oncol 2009; 27 (29) 4839-4847
  • 9 Wun T, White RH. Venous thromboembolism in patients with acute leukemia, lymphoma, and multiple myeloma. Thromb Res 2010; 125 (Suppl. 02) S96-S102
  • 10 Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005; 293 (6) 715-722
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 32 Pabinger I, Thaler J, Ay C. Biomarkers for prediction of venous thromboembolism in cancer. Blood 2013; 122 (12) 2011-2018
  • 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
  • 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
  • 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
  • 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
  • 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
  • 38 Ay C, Dunkler D, Marosi C , et al. Prediction of venous thromboembolism in cancer patients. Blood 2010; 116 (24) 5377-5382
  • 39 Khorana AA. Cancer and coagulation. Am J Hematol 2012; 87 (Suppl. 01) S82-S87
  • 40 Streiff MB, Bockenstedt PL, Cataland SR , et al. Venous thromboembolic disease. J Natl Compr Canc Netw 2013; 11: 1402-1429
  • 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
  • 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
  • 43 Sousou T, Khorana AA. Cancer patients and awareness of venous thromboembolism. Cancer Invest 2010; 28 (1) 44-45
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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