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Venous Thromboembolism in the Cancer Patient

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Cancer patients are at an increased risk of venous thromboembolism. There have been several guidelines published on the topic from the American College of Chest Physicians (ACCP), the American Society of Clinical Oncology (ASCO), and the National Comprehensive Cancer Network (NCCN). Although they agree on some issues regarding prophylaxis and treatment there are several areas that vary. This presentation covers the varying recommendations and the areas of consensus (yellow boxes) among the guidelines while using a patient case to guide their interpretation.

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Venous Thromboembolism in the Cancer Patient

  1. 1. Venous Thromboembolism in the Cancer Patient Marti Larriva PharmD Candidate 2014 December 5, 2013
  2. 2. Outline  Goals  Patient Case  Background  Guidelines  Conclusion of Patient Case
  3. 3. Goals  Understand risk of VTE associated with cancer  Take away where the consensus lies among guidelines  Identify gray areas regarding prophylaxis and treatment of VTE in cancer patients
  4. 4. Patient Case  Ms. M is a 43 y/o female with cervical cancer diagnosed 2 years ago  Undergone 4 lines of chemotherapy with progressive disease and painful lymphadenopathy  TIL harvest surgery – L groin mass 2 months ago  Admitted for TIL therapy:  Chemo -> T-cells -> IL-2 -> Supportive Care  PMH: Diabetes, HTN, PE (1 year ago)  Allergies: Aspirin Relevant Labs BMI 47.5 kg/m2 WBC 5.29 x 109/L Hgb 10.3 g/dL Platelets 306 x 109/L
  5. 5. Background VTE Cancer population Risk Factors Guidelines
  6. 6. Venous Thromboembolism
  7. 7. Armand Trousseau, 1860 Trousseau’s sign of malignancy
  8. 8. What is the difference? Cancer Patients Non-Cancer Patients Ambulatory Ambulatory 8-19% 1.4%
  9. 9. Pathophysiology
  10. 10. Patient Related • Increased Age • Obesity • Co-morbidities • Performance Status Treatment Related • Chemotherapy, antiangiogenesis agents, hormonal therapy • Radiation therapy • Surgery • Indwelling venous access Risk Factors Cancer Related • Primary Site • Stage • Histology • Time since diagnosis Biomarkers • Platelets > 350 x 109/L • Leukocyte count > 11x 109/L • Hgb < 10 g/dL
  11. 11. Treatment Options Heparin, LMWH, Fondapari nux Warfarin
  12. 12. Guidelines ACCP 2012, ASCO 2013, NCCN 2013
  13. 13. Inpatient VTE Prophylaxis ACCP ASCO NCCN *Note: These recommendations are all in the absence of contraindications to anticoagulation.
  14. 14. Nonsurgical VTE Risk Padua Prediction Score Risk Factor Points Active Cancer 3 Previous VTE (excluding SVT) 3 Reduced mobility* 2 Already known thrombophilic condition 1 Recent (≤ 1 mo.) trauma/surgery 1 Elderly age (≥ 70y) 1 Heart and/or respiratory failure 1 Acute MI or ischemic stroke 1 Obesity (BMI ≥ 30) 1 Ongoing hormonal treatment 1 *Anticipated bed rest with bathroom privileges for at least 3 days
  15. 15. Surgical VTE Risk Roger  Operation type  Thoracic area highest risk  Cancer  Disseminated cancer  Chemo within 30 days Caprini  Recent Stroke (<1 mo.)  History of VTE  Age  Malignancy  BMI
  16. 16. Outpatient VTE Prophylaxis ACCP ASCO NCCN *Note: These recommendations are all in the absence of contraindications to anticoagulation.
  17. 17. Multiple Myeloma Low Risk High Risk Thalidomide or Lenalidomide therapy Thalidomide or Lenalidomide therapy in combination with:  High dose dexamethasone  Doxorubicin  Multiagent chemo PLUS 0-1 risk factor for VTE Thalidomide or Lenalidomide therapy PLUS ≥ 2 risk factors for VTE Aspirin 81-325 mg once daily LMWH OR Full dose warfarin (INR 2-3)
  18. 18. Khorana Score Patient Characteristic Risk Score Site of Primary Cancer  Very High Risk (stomach, pancreas)  High Risk (lung, lymphoma, gynecologic, bladder, testicular) 2 1 Prechemotherapy platelet count ≥ 350 x 109/L 1 Hgb < 10 g/dL 1 Prechemotherapy leukocyte count ≥ 11 x 109/L 1 BMI 35 kg/m2 1 Total Score 0 1-2 3 or higher Risk of Symptomatic VTE Low (0.8-3%) Intermediate (1.8-8.4%) High (7.1-41%)
  19. 19. DVT/PE ACCP ASCO NCCN *Note: These recommendations are all in the absence of contraindications to anticoagulation.
  20. 20. Cochrane Collaboration: LMWH vs. Warfarin Analysis 1.6. Comparison 1 LMW H versus VKA, O utcome 6 Recurrent venous thromboembolism. Review: Anticoagulation for the long-term treatment of venous thromboembolism in patients with cancer Comparison: 1 LMWH versus VKA Outcome: 6 Recurrent venous thromboembolism S tudy or subgroup LMWH VKA n/N n/N 4/61 3/30 6.2 % 0.66 [ 0.16, 2.74 ] Hull 2006 7/100 16/100 17.8 % 0.44 [ 0.19, 1.02 ] Lee 2003 27/336 53/336 66.2 % 0.51 [ 0.33, 0.79 ] Meyer 2002 2/71 3/75 4.1 % 0.70 [ 0.12, 4.09 ] Romera 2009 2/36 7/33 5.7 % 0.26 [ 0.06, 1.17 ] Total (95% CI) 604 574 100.0 % 0.49 [ 0.34, 0.70 ] Deitcher 2006 Risk Ratio MH,Random,95% CI Weight Total events: 42 (LMWH), 82 (VKA) Heterogeneity: Tau2 = 0.0; Chi2 = 1.09, df = 4 (P = 0.90); I2 =0.0% Test for overall effect: Z = 3.91 (P = 0.000094) Test for subgroup differences: Not applicable 0.1 0.2 0.5 Favours LMW H 1 2 5 Favours VKA 10 Risk Ratio MH,Random,95% CI
  21. 21. Conclusions Consensus summary Gray areas Future Research
  22. 22. Consensus Summary  Inpatient prophylaxis should consist of prophylactic doses of LMWH, UFH, or Fondaparinux  Outpatient prophylaxis should be done:  In multiple myeloma patients undergoing therapy with thalidomide or lenalidomide  As an extension of inpatient surgical prophylaxis for high risk abdominal or pelvic surgeries  Treatment of DVT/PE should be done using LMWH rather than Warfarin
  23. 23. Gray Areas  Who should receive prophylaxis as an inpatient?  Should outpatients at high risk for VTE receive prophylaxis based upon the Khorana score?  What is the appropriate length of therapy for VTE/PE in the cancer patient?  What factors impact extension of therapy beyond 36 months?
  24. 24. Future Directions for Research  Determine which cancer patients benefit most from thromboprophylaxis:  Risk stratification tools  Specific cancer types  Identify better biomarkers  Determine ideal duration of anticoagulation:  Prophylaxis - Risk related to time from diagnosis  Treatment - Need for extended therapy
  25. 25. Patient Case  Ms. M is a 43 y/o female with cervical cancer diagnosed 2 years ago  Undergone 4 lines of chemotherapy with progressive disease and painful lymphadenopathy  TIL harvest surgery – L groin mass 2 months ago  Admitted for TIL therapy:  Chemo -> T-cells -> IL-2 -> Supportive Care  PMH: Diabetes, HTN, PE (1 year ago)  Allergies: Aspirin Relevant Labs BMI 47.5 kg/m2 WBC 5.29 x 109/L Hgb 10.3 g/dL Platelets 306 x 109/L
  26. 26. Patient Case  Ms. M has a Padua score of 7 indicating she is at high risk for VTE  According to ACCP and NCCN she should receive prophylaxis as an inpatient:  Enoxaparin 40mg SQ Qday  UFH 5,000 units SQ Q8H  Fondaparinux 2.5 mg SQ Qday  Upon discharge, should she continue prophylaxis?  Intermediate Khorana Risk
  27. 27. References 1. Akl EA, Labedi N, Barba M et al. Anticoagulation for the long-term treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst Rev. 2011;(6):CD006650. doi(6):CD006650. 2. Gould MK, Garcia DA, Wren SM et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e227S-77S. 3. Kahn SR, Lim W, Dunn AS et al. Prevention of VTE in nonsurgical patients: Antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e195S-226S. 4. Khorana AA. Cancer-associated thrombosis: Updates and controversies. Hematology Am Soc Hematol Educ Program. 2012;2012:626-30. 5. Lyman GH, Khorana AA, Kuderer NM et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: American society of clinical oncology clinical practice guideline update. J Clin Oncol. 2013;31(17):2189-204. 6. Palumbo A, Rajkumar SV, Dimopoulos MA et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22(2):414-23. 7. Semchuk WM, Sperlich C. Prevention and treatment of venous thromboembolism in patients with cancer. Can Pharm J (Ott). 2012;145(1):24,29.e1. 8. Streiff MB, Bockenstedt PL, Cataland SR et al. Venous thromboembolic disease. J Natl Compr Canc Netw. 2013;11(11):1402-29.
  28. 28. Questions?

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