Lowmolecularweight Heparin without Oral Anticoagulants for the Treatment of Deep Vein Thrombosis

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1 : Venous Thromboembolism – Deep Venous Thrombosis and Pulmonary Embolism 2007 Capital Conference Andrews Air Force Base CDR Kenneth S. Yew MC, USN Uniformed Services University
2 : 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
3 : 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.
4 : DVT – Epidemiology and Etiology Annual incidence of venous thromboembolism (VTE) is 1/1000 DVT accounts for over 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
5 : DVT – VTE Risk Factors 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
6 : DVT – Clinical Presentation Classically = calf pain, tenderness, swelling, redness and Homan’s sign Overall sens/spec = 3-91% Unreliable for diagnostic decisions Up to 50% have none of these 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.
7 : DVT – Wells Score Cancer Paralysis or plaster immobilization Bedrest > 3 d 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 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
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…
9 : 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
10 : 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 Bates SM, Kearon C, Crowther M, et al. Ann Intern Med. 2003;138:787-94 Sensitive d-dimer testing can rule out DVT in low-moderate risk patients
11 : DVT – Case 1 Our patient has a positive quantitative ELISA Unfortunately a positive d-dimer is not helpful diagnostically An imaging study is done…
12 : 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
13 : 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
14 : 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
15 : 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
16 : PE – Clinical Presentation Dyspnea, pleuritic pain and cough most common symptoms Tachypnea, rales and tachycardia most common signs ABG, EKG and CXR May be abnormal Lack specificity to aid diagnosis PIOPED Study. JAMA. 1990;263(20):2753-59. Stein PD, Goldhaber SZ, Henry JW. Chest 1995;107:139-43
17 : 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
18 : PE – Assign 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
19 : PE – Assigning Pretest Probability
20 : PE – Use of D-Dimer 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
21 : 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
22 : PE – Imaging Studies PIOPED study quantified the value of V/Q scans in diagnosing PE Drawbacks: more difficult test and 73% patients had indeterminate scans LE compression US Finding of a DVT completes workup Negative study insufficient to exclude VTE PIOPED Study. JAMA. 1990;263(20):2753-59
23 : 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.
24 : 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.
25 : 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
26 : VTE – Other Therapy Issues Anticoagulation same for DVT & PE Compression stockings prevent post-phlebitic syndrome Thrombolysis - risk/benefit uncertain; clinical outcomes generally not improved Vena cava filters - limited evidence and modest benefit
27 : 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
28 : VTE – Prophylaxis in Medical Patients Indications CHF or severe respiratory disease Bedrest with additional risk factor Cancer Prior VTE Most ICU patients Options Low dose unfractionated heparin or LMWH Sequential compression devices Graduated compression stockings Acute neurologic disease Inflammatory bowel disease
29 : Take Home Points DVT and PE are the same disease Assigning pretest probability for VTE is an essential step in diagnosis A noninvasive testing strategy can result in safe management for most patients suspected of having VTE VTE for can be safely treated with LMWH for at least 5 days and simultaneous warfarin initiation without a loading dose Always consider VTE prophylaxis in inpatients
30 : Questions Which statement about treating VTE is false? a. Untreated patients with PE have a 25% risk of fatal recurrence. b. LMWH is recommended as the initial treatment of choice for both DVT and PE. c. Thrombolytic therapy is generally reserved for severe cases e.g. limb-threatening DVT. d. Vena caval interruption is used in patients with a contraindication to anticoagulation. e. Thrombocytopenia is a risk for patients treated with UFH but not LMWH.
31 : Questions A 35 YOBF returning from a vacation in AK presents with a swollen LLE. No prior hx of similar problems. Homan’s positive, and u/s reveals a noncompressible vein in the L popliteal fossa extending distally. Which of the following is true in this condition? a. Monotherapy with 10 mg load of warfarin is appropriate. b. Enoxaparin (Lovenox) should be administered at a dosage of 1 mg/kg sq bid. c. The incidence of thrombocytopenia is the same with LMWH as UFH. d. Warfarin should be adjusted to maintain the INR at 2.5-3.5. e. Anticoagulant therapy should be started immediately and maintained for 1 year to prevent DVT recurrence.
32 : Questions What reverses the effect of warfarin? – Vitamin A, C, D, E, or K? A 72 YOWM TKA for OA. He is o/w healthy, and on no meds. Which one of the following is most appropriate for prophylaxis against DVT? a. None if no surgical complications b. ASA, 325 mg qd c. UFH, 500 U sq q 12h d. Compressions stockings e. Enoxaparin (Lovenox), 30 mg sq q 12h


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