Review IM R 3 박미나 Overview

Review IM R 3 박미나

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

Dyspnea in cancer patients

Dyspnea in cancer patients • Lung cancer/metastases • • Pleural effusion Congestive heart failure Psychological distress Anemia Pneumonia Muscle weakness Chronic obstructive pulmonary disease Pulmonary embolism

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

Hypercoagulable state associated with malignancy

Malignancy and Venous thromboembolism

Malignancy and VTE • Clinical thromboembolism occurs in as many as 11 % of cancer patients • 2 nd 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

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

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

Does VTE in patients with cancer adversely affect outcome?

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

Venous thromboembolism and Malignancy

NEJM: 351. 2004

Risk for venous thromboembolism • • • 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

DVT and incidence of subsequent symptomatic cancer NEJM: 327, 1992 • 250 patients (secondary DVT: 105, idiopatic DVT: 153), 2 yr • 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

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

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

Diagnosis of venous thromboembolism

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

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

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

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

Treatment of venous thromboembolism

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

Anticoagulant • Unfractionated heparin - continuous infusion after a loading dose Heparin 5000 u(~100 u/kg) ->infusion 1000 -2000 u/hr - monitoring : a. PTT (4 hrly) 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

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

Contraindications to Anticoagulant Tx 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)

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