Proper Diagnosis of Venous Thromboembolism (VTE)

Proper Diagnosis of Venous Thromboembolism (VTE) Whal Lee, M.D. Seoul National University Hospital Department of Radiology 2 nd EFORT Asia Symposium, 3 rd November 2010, Taipei

DVT - Risk Factors Previous DVT or family history of DVT Immobility: such as bed rest or sitting for long periods of time Recent surgery Above the age of 40 Hormone therapy or oral contraceptives Pregnancy or post-partum Previous or current cancer Limb trauma and/or orthopaedic procedures Coagulation abnormalities Obesity

Incidence of DVT After Op Hip fracture: 40% to 70% Total hip replacement: 40% to 70% Total knee replacement: 40% to 70% Urologic surgery: 15% to 20% General and gynecologic surgery: 15% to 20% Neurosurgery: 15% to 20% Medical patients: < 15% Hyers TM: Hull RD: Weg JG. Antithrombotic therapy for venous thromboembolic disease. Chest. 1986;89(suppl2):26S-35S

DVT - Symptoms No symptom In up to 25% of all hospitalized patients: there may be some form of DVT Discoloration of the legs Calf or leg pain or tenderness Swelling of the leg or lower limb Warm skin Surface veins become more visible Leg fatigue Pulmonary embolism

Pulmonary Embolism - Symptoms Dyspnea High heart rate Sweating Chest pain Hemoptysis Syncope Frequently nonspecific Mimic many other cardiopulmonary events Acute RV failure

Pulmonary Embolism 1% patients of DVT die from PE Major cause of PE is DVT If properly diagnosed and treated, the mortality of PE could be markedly decreased

Pulmonary Embolism: Dx Previous Clinical assessment Screening: Perfusion-ventilation scan Definitive diagnosis: Pulmonary angiography

Pulmonary Embolism: Dx Current Clinical assessment Screening: D-dimer Definitive diagnosis: CT

D-dimer Cross-linked fibrin degradation product

D-dimer Indications Suspicion of DVT Suspicion of PE Suspicion of DIC Normal reference range 0-300 ng/ml

D-dimer 93-95% sensitivity and 50% specificity in the diagnosis of thrombotic disease False positive Liver disease High rheumatoid factor Inflammation Malignancy Trauma Pregnancy Recent surgery Advanced age False negative Sample is taken too early after thrombus formation Testing is delayed for several days Presence of anti-coagulation - it prevents thrombus extension Wells PS: Anderson DR: Rodger M: et al. (2003). "Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis". N. Engl. J. Med. 349 (13): 1227 35

Application of D-dimer Pre-test probability Post-test probability D-dimer in PE and DVT D-dimer 93-95% sensitivity and 50% specificity in the diagnosis of thrombotic disease High negative predictive value

Example - Assumption Clinical assessment Low risk group Prevalence 10% Moderate risk group Prevalence 50% High risk group Prevalence 90% Screening test assumption 90% sensitivity 50% specificity

Low Risk Group (Assumption) Pre-test probability : 10% 10 90 Test (+) Test (-) 9 45 1 45 17% 2% Post-test probability 90% sensitivity 50% specificity

Moderate Risk Group (Assumption) Pre-test probability : 50% 50 50 Test (+) Test (-) 45 25 5 25 64% 16% Post-test probability 90% sensitivity 50% specificity

High Risk Group (Assumption) Pre-test probability : 90% 90 10 Test (+) Test (-) 81 5 9 5 94% 64% Post-test probability 90% sensitivity 50% specificity

Wells Score or Criteria for DVT 1. Active cancer (treatment within last 6 months or palliative) -- 1 point 2. Calf swelling >3 cm compared to other calf (measured 10 cm below tibial tuberosity) -- 1 point 3. Collateral superficial veins (non-varicose) -- 1 point 4. Pitting edema (confined to symptomatic leg) -- 1 point 5. Swelling of entire leg -- 1 point 6. Localized pain along distribution of deep venous system -- 1 point 7. Paralysis: paresis: or recent cast immobilization of lower extremities -- 1 point 8. Recently bedridden > 3 days, or major surgery requiring regional or general anaesthetic in past 4 weeks -- 1 point 9. Alternative diagnosis at least as likely -- Subtract 2 points Interpretation: Score of 2 or higher - deep vein thrombosis is likely. Consider imaging the leg veins. Score of less than 2 - deep vein thrombosis is unlikely. Consider blood test such as d-dimer test to further rule out deep vein thrombosis Wells PS: Owen C: Doucette S: Fergusson D: Tran H (2006). "Does this patient have deep vein thrombosis?". JAMA 295 (2): 199 207

Diagnostic Flow Chart - DVT Clinical probability score Low Moderate High D-dimer test Negative Positive Additional testing for DVT or PE Negative Positive Start anticoagulant therapy No DVT or PE Start anticoagulant therapy Additional testing for DVT or PE

Clinical Probability Assessment PE The Wells score (12.5 points) Clinically suspected DVT Alternative diagnosis is less likely than PE Tachycardia Immobilization/surgery in previous four weeks History of DVT or PE Hemoptysis Malignancy (treatment for within 6 months: palliative) - 3.0 points - 3.0 points - 1.5 points - 1.5 points - 1.5 points - 1.0 points - 1.0 points Traditional interpretation Score >6.0 - High (probability 59%) Score 2.0 to 6.0 - Moderate (probability 29%) Score <2.0 - Low (probability 15%) Alternate interpretation Score >4 Score 4 or less - PE likely. Consider diagnostic imaging - PE unlikely. Consider D-dimer to rule out PE

Diagnostic Flow Chart PE Flowchart shows use of quantitative rapid D-dimer ELISA in combination with clinical assessment

PIOPED II Study N Engl J Med 2006;354:2317-27 Prospective multicenter trial enrolling 824 patients Objective: To assess the sensitivity and specificity of multidetector CT angiography in suspected PE Composite reference standard DSA US + Scintigraphy Pretest probability determined using Wells score CT: 4-detector mainly: 16-detector partly

Low Probability & D-dimer (+)

Moderate Probability & D-dimer (+)

High Probability

Imaging Diagnosis of PE CT (MDCT Pulmonary CT angiography) DSA (Digital subtraction angiography) Perfusion-ventilation scan MRI Ultrasound for leg vein CT venography Echocardiography (D-dimer)

Iodine Contrast Perfusion With Dual Source CT

Pulmonary Embolism: Perfusion Defect

Subsegmental Pulmonary Embolism: Perfusion Defect

Deep Vein Thrombosis Ascending venography Filling defect in vein USG Non-compressible echogenic thrombi CT venography MRI

DVT: Role of Imaging Accurate diagnosis Extent of thrombosis Causes Anatomic variations Acute vs. Chronic Treatment planning Catheter-directed Thrombolysis

Ileofemoropopliteal Thrombosis

Normal Deep Vein - USG

Deep Vein Thrombosis

Ultrasound Accurate for thigh DVT Up to 100% Limitations for pelvic and calf DVT No radiation nor contrast media

DVT: CT Venography

May-Thurner

CT Venography: Accuracy Auth Jounal Year Mode N Accuracy Loud AJR 2000 sequential 71 100% Chan Radiology 2000 spiral 116 100% Garg AJR 2000 spiral 70 100/97% Duwe AJR 2000 spiral 74 93% Loud Radiology 2001 spiral 308 97/100% 23% DVT of these had iliac vein and/or IVC involvement

MRI for DVT No flow effect in Spin-echo Gradient-recalled echo Filling defect Gadolinium-enhanced MRV Especially for imaging the pelvic veins in pregnant woman

Post-Thrombotic Syndrome DVT if treated with anti-coagulation alone Clot remains in the leg Vein damage from thrombus-resolving process Symptom Abnormal pooling of blood in the leg Chronic leg pain Fatigue Swelling Severe skin ulcers As many as 60-70 percent of people Within two months of developing DVT

Chronic Venous Disease (CVD) Definition Abnormal functioning of the venous system caused by venous valvular incompetence: may affect the superficial or deep venous system or both

Summary Assessing clinical probability is the first step in diagnosis of DVT or PE D-dimer is good screening tool for DVT or PE with high NPV High false positives in post-op patients! Imaging modalities are comparable to each other for diagnosis of DVT A negative MDCT is safe for ruling out PE at least in non-high clinical probability patients

Thank You!

General Management Co-Chair & Speaker: Dr. Bharat Suman MODY Current appointment: Director and Chief Joint Replacement Surgeon Welcare Hospital, Baroda, India Other appointments: Executive Committee Member, Asia Pacific Arthroplasty Society (APAS) Faculty, SBKS University and Centre for Continuing/Adult Education & Community Services, M.S. University, Baroda, India Specialty / Interests: - Arthroplasty - Arthroscopy

Management of VTE Bharat Mody Director and Chief Joint Replacement Surgeon Welcare Hospital Baroda, India