Venous Thromboembolism: Deep Venous Thrombosis and Pulmonary Embolism 2006 Capital Conference Andrews Air Force Base CDR Kenneth S. Yew MC, USN Uniformed Services University Edited by Paul Saleeb
Objectives • Recognize common presentations of deep venous thrombosis (DVT) and pulmonary embolus (PE) • Understand evidence-based diagnostic and therapeutic strategies for DVT/PE • Understand the role of prevention for DVT/PE and use of prevention strategies
Case 1 • 37 yo moderately obese female on OCP presents to your office with a two day history of painless R leg swelling. She’s been elevating her leg several days after a severe ankle sprain during a mother-daughter soccer game. • No prior medical history, recent surgery or weight loss. She is a non-smoker and drinks rarely. • Exam is notable for R ankle splint and pitting edema in R calf, which is 1.5 cm larger than the L.
DVT – Epidemiology and Etiology • Annual incidence of venous thromboembolism (VTE) is 1/1000 • DVT accounts for one half of VTE • Carefully evaluated, up to 80% of patients with VTE have one or more risk factors • Majority of lower extremity DVT arise from calf veins but ~20% begin in proximal veins • About 20% of calf-limited DVTs will propagate proximally
Malignancy Surgery Trauma Pregnancy Oral contraceptives or hormonal therapy Immobilization Inherited thrombophillia Presence of venous catheter Congestive failure Antiphospholipid antibody syndrome Hyperviscosity Nephrotic syndrome Inflammatory bowel disease DVT – VTE Risk Factors
DVT – Clinical Presentation • Classically = calf pain, tenderness, swelling, redness and Homan’s sign • Overall sens/spec = 3-91% • Unreliable for diagnostic decisions • Wells developed and tested a clinical prediction model for DVT Wells PS, Anderson DR, Bormanis J, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 1997;350 (9094):1795-8.
Cancer Paralysis or plaster immobilization Bedrest > 3d or surgery in past 4 wks Localized tenderness Entire leg swollen Calf > 3cm larger than unaffected leg Pitting edema greater than unaffected leg Collateral superficial veins DVT – Wells Score The following were assigned a point value of 1 if present: • Alternative diagnosis more likely than DVT = - 2 points • Probability High (≥ 3), Moderate (1-2) or Low (0 or less) • DVT risk: High – 75%, Moderate – 17%, Low – 3% Wells PS, Andersen DR, Bormanis J et al. Lancet. 1997;350:1795-8
DVT – Case 1 • Our patient has 2-3 risk factors (OCP, +/- immobilization and trauma • Her Wells score gives her a moderate pretest probability for DVT • A d-dimer test is performed…
DVT – D-Dimer • Fibrin degradation product elevated in active thrombosis • Negative test can help exclude VTE • Preferred test • Quantitative Rapid ELISA – sensitivity 96/95% for DVT/PE • Other methods include latex agglutination and RBC agglutination (SimpliRED) Stein PD, Hull RD, Patel KC, et al. D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Ann Int Med. 2004;140(8):589-602
DVT – D-Dimer • In 283 patients with suspected DVT, low-moderate Wells DVT score and negative d-dimer only 1 (NPV 99.6%) had DVT over next 3 months • Sensitive d-dimer testing can rule out DVT in low-moderate risk patients Bates SM, Kearon C, Crowther M, et al. Ann Intern Med. 2003;138:787-94
DVT – Case 1 • Our patient has a positive quantitative ELISA • Unfortunately a positive d-dimer is not helpful diagnostically • An imaging study is done…
DVT – Imaging • Available imaging and ancillary tests: • Compression US – first line test, high sens/spec • Venography – gold standard • MRI – Lower quality evidence only at present • Impedance plesmythography – not in US • Complete lower extremity US – experimental
DVT – Case 1 • Compression US negative • Options include: • Venography or MRI • Serial compression US – single US done at 5-7 days reliably excludes calf-limited DVT • Follow clinically for resolution of symptoms – riskier, no data supporting safety of this option American Thoracic Society guidelines: The approach to acute venous thromboembolism. Am J Respir Crit Care Med. 1999;160:1043. Fraser JD, Anderson DR. Radiology. 1999;211(1):9-24
Case 2 • The patient in Case 1 elected to be followed clinically. She returned to clinic 3 days later with persistent swelling, but no new symptoms • She was to return the following week, but instead you are called to the ER 10 days later after she presents with acute onset of dyspnea and pleuritic chest pain
PE – Epidemiology and Etiology • 100-200,000 deaths per year due to PE • Most PE arise from lower extremity DVT • In patients with DVT, 40-60% will have a PE on V/Q scanning “Pulmonary embolus is not a disease. It is a complication of DVT.” Ken Moser MD
PE – Clinical Presentation • Dyspnea, pleuritic pain and cough most common symptoms • Tachypnea, rales and tachycardia most common signs • ABG limited value for diagnosis • EKG and CXR often abnormal, but usually lacking specificity to aid diagnosis PIOPED Study. JAMA. 1990;263(20):2753-59. Stein PD, Goldhaber SZ, Henry JW. Chest 1995;107:139-43
CXR FINDINGS • Hampton’s Hump: -wedge-shaped configuration at lung periphery due to infarcted lung Westermark sign: -pulmonary oligemia
PE – Case 2 • Findings in the ER • Alert white female, mildly anxious • T 101, HR 105, RR 18 • R LE edema and redness • Lungs clear to auscultation • ABG – mild respiratory alkalosis; aA gradient = 17 • CXR showing mild atelectasis • D-dimer positive as before, troponin normal
PE – Assigning Pretest Probability • Single most important step in the diagnosis of pulmonary embolism • May be done based on clinical judgment or aided by a clinical scoring system • Modified Wells Criteria is the most widely used and studied • Reliably stratifies patients by likelihood of PE to allow selection of safe (<2% VTE risk if no anticoagulation) management strategy
PE – Use of D-Dimer • Not helpful when positive, but sensitive assay can exclude PE in low risk patient • In patients with moderate pretest probability only rapid quantitative ELISA can adequately exclude PE • Patients judged to be high risk for PE would still have a posttest PE probability of 5-20% even after negative ELISA and require further testing Roy PM, Colombet I, Durieux R, et al. Systematic review and meta-analysis of strategies for the diagnosis of suspected pulmonary embolism. BMJ. 2005;331(7511):259
PE – Case 2 • High risk for PE by Modified Wells Criteria (Wells score = 9) • Positive D-dimer, but negative test would not have safely excluded PE • Options include: • CT angiogram • V/Q scan • Lower extremity compression US
PE – Imaging Studies • PIOPED study quantified the value of V/Q scans in diagnosing PE • Normal/near-normal scans exclude PE in low-moderate risk patients • High probability scans confirm PE in moderate-high risk patients • Drawbacks: more difficult test and 73% patients had indeterminate scans • LE compression US showing DVT helps diagnostically, but a negative study insufficient to exclude VTE PIOPED Study. JAMA. 1990;263(20):2753-59
PE – Helical CT (CTA) • Eng performed a systematic review (SR) of all studies & SRs on CTA prior to 2003 • Only 1/6 SRs and 3/8 primary studies found CTA >90% sensitive for PE • In a similar SR in 2005 Roy concluded • Negative CTA could safely exclude PE in low risk patients • Negative LE US plus negative CTA could exclude PE in moderate risk patients • At the time of those SRs no studies of faster multidetector CTA (MDCT) were available Eng J, Krishnan JA, Segal JB, et al. AJR 2004;183(6):1819-27. Roy PM, Colombet I, Durieux P, et al. BMJ 2005;331(7511):259.
PE – PIOPED II • Published June 2006 in NEJM • 1090 consecutive patients with suspected PE • All given Modified Wells Score • MDCT - mostly 4 slice • Gold standard – composite - V/Q, angiogram & LE US • Findings • MDCT: sens 83% & spec 96% for PE • Positive predictive value >90% in moderate/high risk • Negative predictive value 96% in low risk patients but only 89% in moderate risk patients • Findings generally consistent with Roy’s SR Stein PD, Fowler SE, Goodman LR, et al. Multidetector Computed Tomography for Acute Pulmonary Embolism. N Engl J Med 2006;354(22):2317-2327.
PE – Case 2 • MDCT – segmental embolus • Therapy • Enoxaparin 1mg/kg sq every 12 hours for 5 days • Warfarin started day 1 at 5 mg a day • CBC on day 3-5 and INR every day if inpatient • May stop enoxaparin after 5 days if INR > 2.0 • Warfarin continued to keep INR at 2.5 (2.0-3.0 range) for 3 months
VTE – Other Therapy Issues • Anticoagulation same for DVT & PE • Thrombolysis - risk/benefit uncertain; clinical outcomes generally not improved • Vena cava filters • Contraindication to anticoagulation • Rarely survivors of massive PE • Rare patients with recurrent VTE on adequate anticoagulation • Prophylaxis in certain high risk patients
VTE – Prevention Underutilized • DVT-FREE prospective registry of 5,451 patients at 183 US hospitals • Only 32% of medical patients with DVT received DVT prophylaxis Goldhaber S & Tapson V. Am J Cardiol 2004. Slide adapted from Dr. Michael Streiff. Anderson & Wheeler. Arch Surg 1992. Rahim, et al. Thromb Res 2003. Tapson, et al. Blood 2004
VTE – Prophylaxis in Medical Patients • Indications • CHF or severe respiratory disease • Bedrest with additional risk factor • Cancer • Prior VTE • Acute neurologic disease • Inflammatory bowel disease • Most ICU patients • Options • Low dose unfractionated heparin or LMWH • Sequential compression devices • Graduated compression stockings
Take Home Points • DVT and PE are the same disease • Assigning pretest probability for VTE is an essential step in diagnosis • DVT & PE can diagnosed or excluded in many but not all patients using noninvasive means • VTE for can be safely managed with heparin for at least 5 days and simultaneous warfarin without a loading dose • Always consider VTE prophylaxis in inpatients