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Diagnosis and Risk Stratification

Diagnosis and Risk Stratification. Supplement to Module 4. Overview. Diagnosis of venous thromboembolism Diagnosis of pulmonary embolism Caution regarding use of D-dimer testing in patients with cancer Risk factors for venous thromboembolism in patients with cancer

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Diagnosis and Risk Stratification

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  1. Diagnosis and Risk Stratification Supplement to Module 4

  2. Overview • Diagnosis of venous thromboembolism • Diagnosis of pulmonary embolism • Caution regarding use of D-dimer testing in patients with cancer • Risk factors for venous thromboembolism in patients with cancer • A predictive model for chemotherapy-induced thrombosis

  3. Clinical Manifestations of DVT • DVT cannot be diagnosed based on signs and symptoms alone • Objective testing must be carried out to confirm the diagnosis of DVT 1. Tapson VF et al. Am J Respir Crit Care Med. 1999;160:1043-1066. 2. Haeger K. Angiology. 1969;20:219-223.

  4. Calculating Pretest Probability of DVT Wells PS. J Thromb Thrombolysis. 2006;21:31-40.

  5. Diagnostic Algorithm for DVT (1) Wells PS. J Thromb Thrombolysis. 2006;21:31-40.

  6. Diagnostic Algorithm for DVT (2) Wells PS. J Thromb Thrombolysis. 2006;21:31-40.

  7. Diagnostic Algorithm for DVT (3) Wells PS. J Thromb Thrombolysis. 2006;21:31-40.

  8. Overview • Diagnosis of venous thromboembolism • Diagnosis of pulmonary embolism • Caution regarding use of D-dimer testing in patients with cancer • Risk factors for venous thromboembolism in patients with cancer • A predictive model for chemotherapy-induced thrombosis

  9. Diagnosing PE • PE symptoms are nonspecific and dependent on the size of the emboli1 • Cancer symptoms may obscure the signs and symptoms of PE2 • Objective testing is required to confirm a diagnosis of PE3 1. Schmitt BP et al. J Gen Intern Med. 1986;1:386-393. 2. O'Connell CL et al. J Clin Oncol. 2006;24:4928-4932. 3. Wells PS. J Thromb Thrombolysis. 2006;21:31-40.

  10. Diagnostic Algorithm for PE (1) Wells PS. J Thromb Thrombolysis. 2006;21:31-40.

  11. Diagnostic Algorithm for PE (2) Wells PS. J Thromb Thrombolysis. 2006;21:31-40.

  12. Diagnostic Algorithm for PE (3) Wells PS. J Thromb Thrombolysis. 2006;21:31-40.

  13. Overview • Diagnosis of venous thromboembolism • Diagnosis of pulmonary embolism • Caution regarding use of D-dimer testing in patients with cancer • Risk factors for venous thromboembolism in patients with cancer • A predictive model for chemotherapy-induced thrombosis

  14. D-Dimer Utility in Patients With Cancer • A recent study examined the usefulness of a clinical prediction rule and D-dimer testing to exclude DVT in cancer patients • Low or unlikely pretest probability categories with a negative D-dimer result had very high negative predictive values • May be used to safely rule out DVT in patients with cancer • D-dimer levels are frequently elevated in patients with cancer, even in the absence of DVT • As a result, only 6% of cancer patients in this study had low pretest probability and a negative D-dimer result • Thus, 94% of patients with cancer required further testing to rule out or confirm a diagnosis of DVT even after performing pretest probability testing and D-dimer testing • These data suggest that proceeding directly to other diagnostic studies may be warranted in the majority of patients with cancer Carrier M et al. Thromb Res. 2008.

  15. Overview • Diagnosis of venous thromboembolism • Diagnosis of pulmonary embolism • Caution regarding use of D-dimer testing in patients with cancer • Risk factors for venous thromboembolism in patients with cancer • A predictive model for chemotherapy-induced thrombosis

  16. Increasing age Hospitalization Recent surgery Cancer-specific Advanced stage of cancer Time from diagnosis of cancer (risk elevated during initial period after diagnosis) Site of cancer Cancer therapy Chemotherapy Hormonal therapy Antiangiogenesis agents Erythropoietin Comorbid conditions Infection Obesity Renal disease Pulmonary disease Other risk factors Central venous catheters Prothrombotic mutations Vena caval filters Established Risk Factors for Cancer-Associated VTE Rao MV et al. In: Khorana AA, Francis CW, eds: Cancer-associated thrombosis: New findings in translational science, prevention, and treatment. Informa Healthcare USA. 2008.

  17. Demographic Risk Factors for VTE • Age • Risk for VTE increases with age • In hospitalized cancer patients, rate of VTE was 6.18% among patients aged ≥65 years, compared with 5.1% in younger patients1 • Gender • No significant relationship between gender and VTE in cancer patients2 • Race • No strong evidence for racial disparities in incidence of VTE in cancer patients2 1. Khorana AA et al. J Clin Oncol. 2006;24:484-490. 2. Stein PD et al. Am J Med. 2006;119:60-68.

  18. Incidence of VTE Among Patients Undergoing Cancer Surgery Agnelli G et al. Ann Surg. 2006;243:89-95.

  19. Time Distribution of VTE Among Patients Undergoing Cancer Surgery • Risk for VTE remains even >30 days after cancer surgery • Extended thromboprophylaxis may be warranted in patients with cancer Agnelli G et al. Ann Surg. 2006;243:89-95.

  20. Prognostic Risk Factors for VTE in Cancer Surgery Patients Agnelli G et al. Ann Surg. 2006;243:89-95.

  21. Impact of Cancer Therapy on Risk for VTE Rao MV et al. In: Khorana AA, Francis CW, eds: Cancer-associated thrombosis: New findings in translational science, prevention, and treatment. Informa Healthcare USA. 2008.

  22. Risk for VTE in Patients Receiving Hormonal Therapy Rao MV et al. In: Khorana AA, Francis CW, eds: Cancer-associated thrombosis: New findings in translational science, prevention, and treatment. Informa Healthcare USA. 2008.

  23. Risk for VTE in Patients Receiving Anti-Angiogenic Therapy • As a single agent, the rate of VTE among patients who receive thalidomide is <2% • When combined with dexamethasone or other chemotherapeutic agents, the rate of VTE ranges from 12% to 26%1-4 • Lenalidomide with daily prophylactic aspirin is associated with a lower incidence of VTE even in combination with dexamethasone (3% in 1 study)5 • Early trials reported very high incidences of VTE with bevacizumab in combination with chemotherapy6 • More recent trials suggest that bevacizumab can be incorporated into 5-fluorouracil-containing chemotherapeutic regimens without significantly increasing the risk for VTE7 1. Barlogie B et al. Blood. 2001;98:492-494.2. Rajkumar SV et al. J Clin Oncol. 2006;24:431-436.3. Cavo M et al. Blood. 2002;100:2272-2273.4. Zangari M et al. Blood. 2001;98:1614-1615.5. Rajkumar SV et al. Blood. 2005;106:4050-4053. 6. Shah MA et al. J Clin Oncol. 2005;23:2574-2576.7. Hurwitz H et al. N Engl J Med. 2004;350:2335-2342.

  24. Risk for VTE in Patients Receiving Erythropoietin-Stimulating Agents Bohlius J et al. J Natl Cancer Inst. 2006;98:708-714.

  25. Overview • Diagnosis of venous thromboembolism • Diagnosis of pulmonary embolism • Caution regarding use of D-dimer testing in patients with cancer • Risk factors for venous thromboembolism in patients with cancer • A predictive model for chemotherapy-induced thrombosis

  26. A Predictive Model for Chemotherapy-Associated VTE Khorana AA et al. Blood. 2008;111:4902-4907.

  27. A Predictive Model for Chemotherapy-Associated VTE Khorana AA et al. Blood. 2008;111:4902-4907.

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