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Venous Thromboembolism

Venous Thromboembolism. Justin A. Glass, MD Emory Family Medicine 7.3.08. Objectives. Clinical review of VTE History Prevalence Diagnosis Treatment Prevention . Venous Thromboembolism: DVT. Venous Thromboembolism : PE.

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Venous Thromboembolism

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  1. Venous Thromboembolism Justin A. Glass, MD Emory Family Medicine 7.3.08

  2. Objectives • Clinical review of VTE • History • Prevalence • Diagnosis • Treatment • Prevention

  3. Venous Thromboembolism: DVT

  4. Venous Thromboembolism: PE • An autopsy on Derrick Thomas this morning showed that the nine-time Pro Bowl linebacker died of a blood clot in an artery between his heart and lungs. • Dr. Barth Green -- the neurosurgeon who along with Dr. Frank Eismont had operated on Thomas on Jan. 24 for a spinal cord injury that had left him paralyzed from the chest down – said “It was what is called a saddle embolus” NY Times, 2/10/2000

  5. VTE Prevalence • 600,000 VTE’s in U.S. in 1991 (0.2% of the population) • Incidence is increasing • Why do we care? • 50% of untreated DVT’s will be complicated by a PE • 26% of unrecognized pulmonary embolisms are eventually fatal • 16% of all hospital deaths due to PE • The Worcester DVT Study. Arch Intern Med. 1991;151:933-938.

  6. Venous Thromboembolism

  7. VTE: Pathogenesis • Virchow’s Triad • Venous stasis • Endothelial injury • Hypercoagulability Brotman DJ, Deitcher SR, Lip GY, Matzdorff AC. Virchow's triad revisited. South Med J. 2004;97:213-214.

  8. VTE Risks • Increasing age • Cancer • Pregnancy • 60/100,000 women • Immobility • Surgery • Hormone replacement therapy / OCP’s • 10-30 / 100,000 users vs 4-8/100,000 non-users • Thrombophilic disorders

  9. Maria • 38 yr old female presents with pain and mild swelling in L LE. Pt was hiking recently when she slipped, fell and injured R knee. Her knee immediately swelled. She felt unstable w/ walking due to pain and sought care at a local ER. A knee immobilizer was placed. She followed up with an orthopedic doctor who diagnosed an acute ACL rupture. An MRI confirmed this and she underwent allograph repair 3 weeks ago. She is currently doing rehab with a PT.

  10. Maria (cont) • PMH: Negative • PSH: ACL repair (6/12/08) • Meds: Ibuprofen prn / Vicodin prn / Ortho Tricyclen • Allergies: NKDA • Soc Hx: Scrub tech at EUH No Tob / Rare Etoh

  11. Maria on exam • Vitals: T 97.2 P 90 BP 110/70 R 14 • Pulm: CTA • CV: Regular • Ext: Moderate swelling about R knee w/ healing incision. 1+ pitting edema L LE. Mild pain with squeezing calf on L leg. None on R leg. Negative Homan’s sign. Calf circumference is 1 cm larger L than R.

  12. DVT - Physical Exam Calf tenderness Homan’s Sign Differential Swelling www.netterimages.com

  13. What is the probability that Maria has a DVT?

  14. Diagnosis • Well’s Criteria (DVT) • Active cancer (tx within <6 mos or palliative care) (1) • Calf swelling (3 cm difference – 10 cm below tib tub) (1) • Collateral superficial veins (1) • Paralysis, paresis, or recent immobilization LE (1) • Pitting edema confined to involved leg (1) • Bedridden within 3 days or surgery w/ anes <12 wks (1) • Swollen leg (1) • Alternate diagnosis more likely (-2) Probability: Low (0 pts) Intermediate (1-2) High (3) Lancet 2002;350:1796.

  15. D-Dimer • Clinical utility in VTE diagnosis?

  16. D-Dimer • If D-Dimer is measured by ELISA or immunoturbidimetric method, it is highly sensitive for active VTE. • Most studies use cutoff <500 ng/mL • Sensitivity 96-100% • If D-Dimer is measured by semiquantitative latex agglutination, it is not highly sensitive.

  17. D-Dimer • A low clinical probability by Well’s Criteria plus a normal D-Dimer implies a LOW clinical risk of VTE. • 0.5% of patients develop DVT in 3 months • Further testing can be deferred in this patient population. Fancher TL, White RH, Kravitz RL. Combined use of rapid D-dimer testing and estimation of clinical probability in the diagnosis of DVT: systematic review. BMJ. 2004;329:821 Ann Fam Med 2007;5:57-62.

  18. D-Dimer • What is the risk of DVT in a patient with a normal D-Dimer and a moderate or high risk Well’s score? • Moderate: 3.5% • High risk: 21% Fancher TL, White RH, Kravitz RL. Combined use of rapid D-dimer testing and estimation of clinical probability in the diagnosis of DVT: systematic review. BMJ. 2004;329:821.

  19. VTE Diagnosis: Ultrasonography • Duplex scan of LE • Compressibility of the vein • Doppler flow within the vein • Symptomatic patient with proximal LE DVT • Sensitivity: 89-96% • Specificity: 94-99%

  20. VTE Diagnosis: Ultrasonography • Asymptomatic patient with proximal LE DVT • Sensitivity: 47-62% • Symptomatic patient with distal LE DVT • Sensitivity: 73-93%

  21. VTE Diagnosis: Venography • Gold standard for DVT • Primarily a research tool now

  22. Anatomy of the Deep Venous System

  23. Albert • 62 yr old male presents to the ER with complaint of pleuritic CP. Present x 1 day. No injury. Feels SOB with walking. No fever. No cough. No LE pain. • PMH: Colon CA s/p L colectomy 4/08 / HTN / BPH • Meds: Lisinopril / Tamsulosin / ASA / MVI • NKDA • Soc Hx: No Tob / No Etoh

  24. Albert • Physical • T 99.1 P 110 BP 135/85 R 22 O2 sat 95% RA • Pulm: CTA good AF • CV: Regular No murmurs • Ext: No edema. Negative Homan’s sign

  25. Albert • What is the likelihood of a PE?

  26. Diagnosis of PE: Common findings • History • Dyspnea (73%) • Pleuritic Chest pain (66%) • Cough (37%) • Hemoptysis (13%) • Physical • Tachypnea (70%) • Rales (51%) • Tachycardia (30%) Stein, PD, et al. Chest 1991 Sep;100(3):598-603. Stein, PD, et al. Am J Cardiol 1991; 68:1723-

  27. Diagnosis • Well’s Criteria (PE) • Cancer (1) • Hemoptysis (1) • Heart rate more than 100 (1.5) • Previous episode of VTE (1.5) • Recent surgery or immobilization (1.5) • Alternate diagnosis less likely than PE (3) • Clinical signs of DVT (3) Probability: Low (0-1) Intermediate (2-6) High (7+) Am J Med 2002;113:270.

  28. Diagnosis of PE: Common findings • D-Dimer elevation • >500 ng/ml • A-a gradient >20 mm Hg • (713(FIO2) – PaCO2/0.8) – PaO2 • BNP or proBNP elevation • Sensitivity and Specificity are approx 60% • Troponin elevation • 30-50% of mod/large PE’s have troponin elevation

  29. Albert - EKG

  30. farm1.static.flickr.com/4/9263629_156f0cb46d.jpg

  31. PE: Definitive Testing • What test should be ordered?

  32. PE: Definitive Testing • VQ Scan • Spiral CT Chest • Pulmonary angiography

  33. Ventilation – Perfusion (VQ) Scan

  34. VQ Scan www.imagingpathways.health.wa.gov.au/.../vq.jpg

  35. VQ Scanning • Nuclear medicine scan to detect perfusion-ventilation mismatch. • Indeterminate • Normal • Low probability • Intermediate probability • High probability

  36. Likelihood of PE based on VQ Result Clinical Probability of PE VQ Scan Result High Intermediate Low High 95 86 56 Intermediate 66 28 15 Low 40 15 4 Normal 0 6 2 Value of the VQ scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators. JAMA 1990 May 23-30;263(20):2753-9.

  37. Diagnosis of VTE: Spiral CT Chest • Detection of pulmonary embolism by timed application of contrast to the pulmonary vasculature • Heterogenity in results across trials. • Sensitivity: 40-100% (PIOPED 2: 83%) • Specificity: 78-100% (PIOPED 2: 96%) Segal J, Eng J, Tamariz L, Bass E. Review of the evidence on diagnosis of deep venous thrombosis and pulmonary embolism. Ann Fam Med. 2007;5:63-73.

  38. Spiral CT www.imagingpathways.health.wa.gov.au/.../vq.jpg

  39. Diagnosis of VTE: Spiral CT Chest • PIOPED 2 Study Clinical Probability of PE CT ResultLowIntermediateHigh Positive for PE 58% 92% 98% Negative for PE 4% 11% 40% Table show % with PE by “composite reference standard” N Engl J Med 2006;354:2317-27.

  40. Diagnosis of VTE: Spiral CT Chest • PIOPED 2 Study Clinical Probability of PE CT ResultLowIntermediateHigh Positive for PE 58% 92% 98% Negative for PE 4% 11%40% Table show % with PE by “composite reference standard” N Engl J Med 2006;354:2317-27.

  41. PE Diagnosis • VQ scanning versus Spiral CT Chest • Randomized trial of patients suspected of having PE, n=1471 False Negative Rate Spiral CT 0.6% VQ Scan 1.0%

  42. VTE Diagnosis • What should you do if you have a patient with a high probability Well’s score for PE and a negative spiral CT Chest? • Single or sequential duplex scan of the LE OR • Pulmonary angiography

  43. PE Diagnosis • Christopher Study (n=3306) • Well’s score obtained. Two cohorts defined • Well’s 4 or less (PE unlikely) • Well’s >4 (PE likely) • D-Dimer obtained if Well’s 4 or less • If Well’s 4 or less and D-Dimer negative, conclude - no PE • If Well’s 4 or less and D-Dimer positive, obtain Spiral CT • If Well’s >4, obtain Spiral CT JAMA. 2006;295:172-179

  44. PE Diagnosis Christopher Study (cont) Initial WorkupFollow-up: 3 months Low Risk Well’s / Negative D-Dimer 0.5% with PE No Spiral CT done Negative Spiral CT 1.3% with PE Positive Spiral CT initially 3.0% with PE

  45. Treatment of DVT • Low Molecular Weight Heparin (LMWH) • 1 mg/kg q 12 hrs or 1.5 mg/kg q 24 hrs • Coumadin x 3 months (Goal INR 2-3) • LMWH should be overlapped until both of the following conditions are met: • INR >2 x days • At least five days of LMWH given • Pressure stockings

  46. Treatment of PE • Refer to DVT guidelines, with addition of: • Unfractionated heparin is considered equal option to LMWH. • Heparin dosing should be adjusted to achieve aPTT 1.5-2.5 x the upper limit of normal. • Strict guidelines need to be in place to prevent undercoagulation or overcoagulation

  47. Unfractionated heparin • Weight based nomogram 1. Bolus 80 units/kg then continuous infusion at 18 units/kg. 2. Check aPTT 6 hrs aPTT <35 (<1.2 x control): Bolus 80 units/kg and increase infusion by 4 units/kg aPTT 35-45 (1.2 – 1.5 x control): Bolus 40 units/kg then increase by 2 units/kg/hr aPTT 46-70 (1.5-2.3 x control): No change aPTT 71-90 (2.3 – 3.0 x control): Decrease infusion by 2 units/kg/hr aPTT 90+ (>3.0 x control): Hold infusion x 1 hour, then decrease infusion by 3 units/kg/hr 3. Return to step #2 if dose change. 4. If no dose change, check aPTT q 24 hrs

  48. Unfractioned Heparin vs LMWH • Meta-analyses have shown: • Lower recurrence DVT (2.7% vs 7.0%) • Lower incidence major bleeding (0.9% vs 3.2%) • Lower death rate at 3 months (OR 0.71 (0.53-0.94)) (All favoring LMWH) Am J Med 1996 Mar;100(3):269-77 Ann Intern Med 1999 May 18;130(10):800-9

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