1. Review IM R3 박미나

2. Dyspnea in cancer patients Hypercoagulable state associated with malignancy Diagnosis of venous thromboembolism Treatment of venous thromboembolism Overview

3. Dyspnea in cancer patients

4. Lung cancer/metastases Pleural effusion Congestive heart failure Psychological distress Anemia Pneumonia Muscle weakness Chronic obstructive pulmonary disease Pulmonary embolism

6. Lung cancer/metastases Pleural effusion Congestive heart failure Psychological distress Anemia Pneumonia Muscle weakness Chronic obstructive pulmonary disease Pulmonary embolism transfusion anticoagulant antibiotics Improve the subjective symptom local control(bronchial stent) chemotherapy pleurodesis

7. Hypercoagulable state associated with malignancy

8. and Malignancy Venous thromboembolism

9. Malignancy and VTE Clinical thromboembolism occurs in as many as 11 % of cancer patients 2nd leading cause of death in patients with malignancy Evidence of thorombosis in 30% of patients who died of pancreas cancer Gastrointestinal tract, ovary, prostate, lung cancer

10. Tissue factor Procoagulant activity of cancer cells Cytokine Monocyte Endothelial cells Cormobid factor : surgery, immobilization, venous obstruction, catheter Chemotherapeutic agents: L-asparaginase, tamoxifen Pathogenesis of hypercoagulable state

11. Clinical manifestation of thrombosis in cancer patients Idiopathic DVT and other venous thrombosis - chemotherapy, hormonal therapy, surgery, immobilization, catheter Disseminated intravascular coagulation (DIC) - hematologic malignancy, metastatic cancer Arterial thrombosis – endocarditis Thrombotic microangiopathy Migratory superficial thrombophlebitis

12. Does VTE in patients with cancer adversely affect outcome?

14. Probability of death within 183 days of initial hospital admission in patients with cancer with or without concurrent VTE

15. and Malignancy Venous thromboembolism

16. NEJM:351.2004

17. Old age 17% Malignancy 15.3% History of thromboembolism Surgery Immobilization Of all patients presenting with acute VTE 15-20% are known to have cancer 2-5% are diagnosed with concurrent cancer on initial examination 5-10% are diagnosed with cancer during follow up Risk for venous thromboembolism

18. DVT and incidence of subsequent symptomatic cancer NEJM:327,1992 250 patients (secondary DVT:105, idiopatic DVT:153), 2yr cancer : secondary DVT-> 0 of 105 pts (1.7%) idiopatic DVT-> 5 of 145 pts (3.3%) overt cancer developed during F/U : secondary DVT-> 2 of 105 pts (1.9%) idiopatic DVT->11 of 145 pts (7.6%) 35 idiopatic DVT, recurrent thromboembolism overt cancer->6 of the 35 (17.1 %) idiopathic venous thrombosis, recurrent thromboembolism -> subsequent development of clinically overt cancer

19. Search for occult malignancy in patients with deep venous thrombosis. Swiss Med Wkly :133, 2003 Prevalence and incidence of cancer were higher in IDVT patients compared to those with SDVT. Combining patient history, clinical examination, simple laboratory tests, and a routine chest x-ray is an appropriate strategy to detect underlying cancer in patients with IDVT. Routine abdominal ultrasound can safely be omitted. Extensive screening for occult malignant disease in idiopathic venous thromboembolism Journal of Thrombosis and Haemostasis 2, 2004 Although early detection of occult cancers may be associated with improved treatment possibilities, it is uncertain whether this improves the prognosis.

20. Use of screening Absence of prospective study demonstrating improved survival with aggressive diagnostic testing Recurrent thrombosis and abnormal clinical findings =>the most likely indicators of underlying malignancy Chest radiograph, CT of chest and abdomen, stool occult blood, CEA, PSA, ά-FP

21. Diagnosis of venous thromboembolism

22. Symptoms and sign of venous thromboembolism Dyspnea, chest pain, tachypnea, hemoptysis, wheezing, palpitation, anxiety Leg swelling, leg pain, reddish blue discoloration, Homan’s sign

24. Evaluation of DVT in malignancy Disease status evaluation of malignancy Color doppler ultrasonography of lower extremity Drug history taking- oral pill, tamoxifen CBC/DC, DIC lab, D-dimer Chest X-ray, ECG If needed, lung perfusion scan

25. Dx of deep vein thrombosis Suspected DVT Ultrasound Management options Tx for DVT D-dimer DVT excluded One week Ultrasound Tx for DVT DVT excluded Consider clinical probability Mod/high Low - + +- + -

26. Dx of pulmonary thromboembolism Suspected PE Lung scan Ultrasound PE excluded Management options Consider clinical probability Mod/highLow Treat for PE Pulmonary angiogram Consider clinical probability D-dimer Serial ultrasound Treat for PEPE excluded Serial US or pulmonary angio Treat for PE Non high probability NL High probability Low/mod High + + + - - -

27. Treatment of venous thromboembolism

28. Thrombolytics massive PE with cardiovascular collapse, low risk of bleeding streptokinase, urokinase, recombinant tPA Anticoagulants unfractionated heparin low molecular weight heparin oral anticoaculat IVC filter

29. Anticoagulant Unfractionated heparin - continuous infusion after a loading dose Heparin 5000u(~100u/kg) ->infusion 1000-2000u/hr - monitoring : aPTT (4hrly) 2.5-3.5 Low-Molecular-Weight Heparin - effective, safe, out patients therapy - less bleeding, less nonspecific binding, less thrombocytopenia, less osteoporosis - S.C, once or twice Oral anticoagulant (warfarin or another coumarin) - INR 2.0-3.0 - heparin can be discontinued after 5 days

30. Inferior vena cava filter Pts with contraindications to anticoagulation Recurrent venous thrombosis despite intensive anticoagulation

31. Absolute contraindications Active bleeding Severe bleeding diathesis or platelet count ≤20,000/mm 3 Neurosurgery, ocular surgery, or intracranial bleeding (within the past 10 days) Contraindications to Anticoagulant Tx

32. Relative contraindications Mild-to-moderate bleeding diathesis, thrombocytopenia Brain metastases Recent major trauma Major abdominal surgery (within past 2 days) Gastrointestinal or genitourinary bleeding (within past 14 days) Endocarditis Severe hypertension