Thromb Haemost 2017; 117(06): 1192-1198
DOI: 10.1160/TH16-11-0840
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

Predictors of active cancer thromboembolic outcomes

RIETE experience of the Khorana score in cancer-associated thrombosis
Alfonso J. Tafur
1   NorthShore University Health Systems, Evanston, Illinois, USA
,
Joseph A. Caprini
1   NorthShore University Health Systems, Evanston, Illinois, USA
,
Lauren Cote
1   NorthShore University Health Systems, Evanston, Illinois, USA
,
Javier Trujillo-Santos
2   Department of Internal Medicine, Hospital General Universitario Santa Lucia, Murcia, Spain
,
Jorge Del Toro
3   Department of Internal Medicine, Hospital General Universitario Gregorio Maranon, Madrid, Spain
,
Fernando Garcia-Bragado
4   Department of Internal Medicine, Hospital Universitari de Girona Dr Josep Trueta, Gerona, Spain
,
Carles Tolosa
5   Department of Internal Medicine, Corporación Sanitaria Parc Tauli, Barcelona, Spain
,
Giovanni Barillari
6   Department of Internal Medicine, Ospedale S.Maria della Misericordia, Udine, Italy
,
Adriana Visona
7   Department of Vascular Medicine, Ospedale Castelfranco Veneto, Castelfranco Veneto, Italy
,
Manuel Monreal
8   Department of Internal Medicine, Hospital de Badalona Germans Trias i Pujol, Universidad Católica de Murcia, Spain
,
the RIETE Investigators › Author Affiliations
Further Information

Publication History

Received: 07 November 2016

Accepted after major revision: 23 February 2017

Publication Date:
28 November 2017 (online)

Summary

Even though the Khorana risk score (KRS) has been validated to predict against the development of VTE among patients with cancer, it has a low positive predictive value. It is also unknown whether the score predicts outcomes in patients with cancer with established VTE. We selected a cohort of patients with active cancer from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry to assess the prognostic value of the KRS at inception in predicting the likelihood of VTE recurrences, major bleeding and mortality during the course of anticoagulant therapy. We analysed 7948 consecutive patients with cancer-associated VTE. Of these, 2253 (28 %) scored 0 points, 4550 (57 %) 1–2 points and 1145 (14 %) scored ≥3 points. During the course of anticoagulation, amongst patient with low, moderate and high risk KRS, the rate of VTE recurrences was of 6.21 (95 %CI: 4.99–7.63), 11.2 (95 %CI: 9.91–12.7) and 19.4 (95 %CI: 15.4–24.1) events per 100 patient-years; the rate of major bleeding of 5.24 (95 %CI: 4.13–6.56), 10.3 (95 %CI: 9.02–11.7) and 19.4 (95 %CI: 15.4–24.1) bleeds per 100 patient-years and the mortality rate of 25.3 (95 %CI: 22.8–28.0), 58.5 (95 %CI: 55.5–61.7) and 120 (95 %CI: 110–131) deaths per 100 patient-years, respectively. The C-statistic was 0.53 (0.50–0.56) for recurrent VTE, 0.56 (95 %CI: 0.54–0.59) for major bleeding and 0.54 (95 %CI: 0.52–0.56) for death. In conclusion, most VTEs occur in patients with low or moderate risk scores. The KRS did not accurately predict VTE recurrence, major bleeding, or mortality among patients with cancer-associated thrombosis.

* A full list of the RIETE Investigators appears in the Appendix.


 
  • References

  • 1 Posch F, Riedl J, Reitter EM. et al. Hypercoagulabilty, venous thromboembolism, and death in patients with cancer. A Multi-State Model. Thromb Haemost 2016; 115: 817-826.
  • 2 Timp JF, Braekkan SK, Versteeg HH. et al. Epidemiology of cancer-associated venous thrombosis. Blood 2013; 122: 1712-1723.
  • 3 Phan M, John S, Casanegra AI. et al. Primary venous thromboembolism prophylaxis in patients with solid tumours: a meta-analysis. J Thromb Thrombolysis 2014; 38: 241-249.
  • 4 Connors JM. Prophylaxis against venous thromboembolism in ambulatory patients with cancer. N Eng J Med 2014; 370: 2515-2519.
  • 5 Khorana AA, Kuderer NM, Culakova E. et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; 111: 4902-4907.
  • 6 Khorana AA, Carrier M, Garcia DA. et al. Guidance for the prevention and treatment of cancer-associated venous thromboembolism. J Thromb Thrombolysis 2016; 41: 81-91.
  • 7 Lyman GH, Bohlke K, Khorana AA. et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: american society of clinical oncology clinical practice guideline update 2014. J Clin Oncol 2015; 33: 654-656.
  • 8 Mansfield A, Tafur AJ, Wang CE. et al. Predictors of Active Cancer thromboembolic Outcomes: Validation of the Khorana Score among Patients with Lung Cancer. J Thromb Haemost. 2016 Epub ahead of print.
  • 9 Macbeth F, Noble S, Evans J. et al. Randomized Phase III Trial of Standard Therapy Plus Low Molecular Weight Heparin in Patients With Lung Cancer: FRAGMATIC Trial. J Clin Oncol 2016; 34: 488-494.
  • 10 Kuderer NM, Culakova E, Lyman GH. et al. A Validated Risk Score for Venous Thromboembolism Is Predictive of Cancer Progression and Mortality. Oncologist 2016; 21: 861-867.
  • 11 Francis CW, Kessler CM, Goldhaber SZ. et al. Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12 months: the DALTECAN Study. J Thromb Haemost 2015; 13: 1028-1035.
  • 12 Maestre A, Trujillo-Santos J, Visona A. et al. D-dimer levels and 90-day outcome in patients with acute pulmonary embolism with or without cancer. Thromb Res 2014; 133: 384-389.
  • 13 Spiezia L, Campello E, Trujillo-Santos J. et al. The impact of disseminated intravascular coagulation on the outcome of cancer patients with venous thromboembolism. Blood Coagul Fibrinolysis 2015; 26: 709-711.
  • 14 Farge D, Trujillo-Santos J, Debourdeau P. et al. Fatal Events in Cancer Patients Receiving Anticoagulant Therapy for Venous Thromboembolism. Medicine 2015; 94: e1235.
  • 15 Remy-Jardin M, Remy J, Wattinne L. et al. Central pulmonary thromboembolism: diagnosis with spiral volumetric CT with the single-breath-hold technique--comparison with pulmonary angiography. Radiology 1992; 185: 381-387.
  • 16 Prandoni P, Cogo A, Bernardi E. et al. A simple ultrasound approach for detection of recurrent proximal-vein thrombosis. Circulation 1993; 88: 1730-1735.
  • 17 Agnelli G, George DJ, Kakkar AK. et al. Semuloparin for thromboprophylaxis in patients receiving chemotherapy for cancer. N Eng J Med 2012; 366: 601-609.
  • 18 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. 2011 118. abstr206 2011.
  • 19 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: 448-454.
  • 20 Lee AY, Kamphuisen PW, Meyer G. et al. Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. J Am Med Assoc 2015; 314: 677-686.
  • 21 Khorana A, Bauersachs R, Kamphuisen P. et al. Clinical predictors of recurrent venous thromboembolism (VTE) in cancer patients from a randomized trial of long-term tinzaparin versus warfarin for treatment: The CATCH study. J Clin Oncol. 2015 33. (Suppl): abstr 9621.
  • 22 Napolitano M, Saccullo G, Malato A. et al. Optimal duration of low molecular weight heparin for the treatment of cancer-related deep vein thrombosis: the Cancer-DACUS Study. J Clin Oncol 2014; 32: 3607-3612.
  • 23 Tafur AJ, McBane R, Wysokinski WE. et al. Predictors of major bleeding in peri-procedural anticoagulation management. J Thromb Haemost 2012; 10: 261-267.
  • 24 Tafur AJ, Wysokinski WE, McBane RD. et al. Cancer effect on periprocedural thromboembolism and bleeding in anticoagulated patients. Ann Oncol 2012; 23: 1998-2005.
  • 25 Prandoni P, Lensing AW, Piccioli A. et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100: 3484-3488.
  • 26 Klok FA, Niemann C, Dellas C. et al. Performance of five different bleeding-prediction scores in patients with acute pulmonary embolism. J Thromb Thrombolysis 2016; 41: 312-320.
  • 27 Sohal DP, Shrotriya S, Glass KT. et al. Predicting early mortality in resectable pancreatic adenocarcinoma: A cohort study. Cancer 2015; 121: 1779-1784.