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Thromboembolism

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Associate Professor Samuel Galvagno: Thromboembolism.
From CICM ASM PROGRAM 2019.

Published in: Health & Medicine
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Thromboembolism

  1. 1. R ADAMS COWLEY SHOCK TRAUMA CENTER All Bleeding Stops Eventually Thromboembolism Sam Galvagno, DO, PhD, FCCM Col, USAF, MC, SFS Associate Professor Medical Director, Lung Rescue Unit (LRU) Director, Shock Trauma Go-Team University of Maryland School of Medicine R Adams Cowley Shock Trauma Center Baltimore, MD, USA
  2. 2. R ADAMS COWLEY SHOCK TRAUMA CENTER Disclosures • United States Air Force Reserve • UpToDate® Author • Department of Defense Funding
  3. 3. R ADAMS COWLEY SHOCK TRAUMA CENTER Objectives • Examine pathophysiological mechanisms responsible for VTE in trauma patients • List risk factors for and incidence of VTE • Evaluate evidence-based recommendations for prevention and management
  4. 4. R ADAMS COWLEY SHOCK TRAUMA CENTER Incidence • 0.1-0.2% of population per year • > 60% DVT risk when no VTE prophylaxis given • 16.5% with pulmonary embolism (autopsy) Beckman MG. Am J Prev Med 2010; 38(4). Sevitt S. Br J Surg 1961; 48. Geerts WH. N Engl J Med 1994; 331(24). Rogers FB. J Trauma 2002; 53.
  5. 5. R ADAMS COWLEY SHOCK TRAUMA CENTER Pathophysiology and Risk Factors
  6. 6. R ADAMS COWLEY SHOCK TRAUMA CENTER Pathophysiology Semin Nucl Med. 2001; 31(2). Crit Care Clin. 2011; 27(4). Circulation. 2003; 107(23 Suppl 1).
  7. 7. R ADAMS COWLEY SHOCK TRAUMA CENTER Practice management guidelines for the prevention of venous thromboembolism in trauma patients: The EAST practice management guidelines work group Rogers FB, Cipolle MD, Velmahos G, Rozychi G, Luchette FAet al. University of Vermont, USA J Trauma 2002; 53: 142-164. Risk factors • Spinal fractures • Spinal cord injury • Older age • Higher ISS • ? Long bone / pelvic fractures • ?? TBI ??
  8. 8. R ADAMS COWLEY SHOCK TRAUMA CENTER Venous thromboembolic events in critically ill traumatic brain injury patients Skrifvars MB, Baily M, et al. (ANZICS Clinical Trials Group)al. Australia and New Zealand Intensive Care Research Centre, Melbourne, Australia Int Care Med 2017; 43: 419-428. • EPO-TBI Trial • Enoxaparin 40 mg once daily • Received by 75% • VTE rate 4x higher than general medical and surgical populations • 1/5 TBI patients developed DVT or PE • 4-5 days until pharmacological prophylaxis started • Limitations: mobilization status, aFXa levels unknown, once daily dosing
  9. 9. R ADAMS COWLEY SHOCK TRAUMA CENTER Wells Criteria Wells PS. N Engl J Med 2003; 349. Modi S. World J Emerg Surg 2016; 11.
  10. 10. R ADAMS COWLEY SHOCK TRAUMA CENTER Wells Score in Trauma Modi S. World J Emerg Surg 2016; 11.
  11. 11. R ADAMS COWLEY SHOCK TRAUMA CENTER Greenfield Risk Assessment Profile (RAP) Greenfield LJ. J Trauma 1997. ≥10
  12. 12. R ADAMS COWLEY SHOCK TRAUMA CENTER Pharmaceutical Prophylaxis
  13. 13. R ADAMS COWLEY SHOCK TRAUMA CENTER LMWH vs. Heparin LMWH • ↑ Bioavailability • ↓ Protein binding • ↑ Predictability • ↑ Half-life • ↓ Risk of HIT (0.6%) • ↓ Osteoporosis • ↓ Risk of bleeding • ↑ Cost • ↓ Clearance in renal failure Unfractionated • ↓ Half-life • ↓ Predictability • ↓ Bioavailability • ↑ Risk of HIT (2.6%) • ↓ Cost
  14. 14. R ADAMS COWLEY SHOCK TRAUMA CENTER Unfractionated heparin vs. low-molecular weight heparin for venous thromboembolism prophylaxis in trauma Jacobs BN, Cain-Nielsen, AH, Jakubus, JL, et al.et al. University of Michigan, USA J Trauma Acute Care Surg 2017; 83: 151-158. LMWH vs. Unfractionated (properly dosed)
  15. 15. R ADAMS COWLEY SHOCK TRAUMA CENTER Relation of antifactory-Xa peak levels and venous thromboembolism after trauma Karcutskie CA, Dharmaraja A, Patel J, et al.et al. University of Miami Jackson Memorial (Ryder Trauma Center), USA J Trauma Acute Care Surg 2017; 83: 1102-1107.. Optimal dosing for LMWH? • Anti Xa level ≥ 0.2-0.4 IU/mL considered “prophylactic” • Nearly half were never > 0.2 • No difference between VTE, DVT, PE rates in subprophylactic vs prophylactic
  16. 16. R ADAMS COWLEY SHOCK TRAUMA CENTER Utility of anti-factor Xa monitoring in surgical patients receiving prophylactic doses of enoxaparin for venous thromboembolism prophylaxis Pannucci CJ, Prazak AM, Scheefer Mal. University of Utah, USA AM J Surg 2017; 213: 1143-1152. Optimal dosing for LMWH? • 30 mg BID in range aFXa 29-66% of time • 0.6 mg/kg BID dose better (weight based) • Burns  0.5 mg/kg • More patients in range
  17. 17. R ADAMS COWLEY SHOCK TRAUMA CENTER Anti-Xa–guided enoxaparin thromboprophylaxis reduces rate of deep venous thromboembolism in high-risk trauma patients Singer GA, Riggi G, Karcutskie CA, et al.al. University of Miami, FL, USA J Trauma Acute Care Surg 2016; 81: 1101-1108. • Prospective, observational, case-control • aFXa-guided enoxaparin for high risk trauma patients • Goal 0.2-0.4 IU/mL • 30 mg BID  ↑10 mg to goal • Risk factors for subtherapeutic: • BMI, ISS, RAP > 10 • DVT risk ↓ compared to historical cohort • 7.1 vs 20.5%
  18. 18. R ADAMS COWLEY SHOCK TRAUMA CENTER Low-molecular weight heparin venous thromboprophylaxis in critically ill patients with renal dysfunction (PROTECT trial) Pai M, Adhikari NKJ, Osterman M, (PROTECT Investigators)al. Maastricht University, Netherlands PLoS One 2018: 1-15. • Preplanned subgroup study • Patients with end-stage renal disease • Dalteparin vs. unfractionated heparin • No difference in proximal DVT, major bleeding except in patients with severe renal failure • CrCl < 30 mL/min--> higher risk for VTE • 7.6% vs. 3.7%, P = 0.04
  19. 19. R ADAMS COWLEY SHOCK TRAUMA CENTER Reversal? Clinical Practice Guideline on Anticoagulant Dosing and Management. American Society of Hematology / American College of Chest Physicians, 8th Edition. 2011.
  20. 20. R ADAMS COWLEY SHOCK TRAUMA CENTER General Summary • Drug of choice: LMWH • Start 24 hrs. post injury if possible • Twice a day best • 0.5-0.6 mg/kg • Check aFXa levels • Goal: > 0.2 (to 0.4) IU/mL • Adjust by 10 mg if needed (↑/↓) • Protamine can reverse (partially) • Caution in renal failure
  21. 21. R ADAMS COWLEY SHOCK TRAUMA CENTER TBI
  22. 22. R ADAMS COWLEY SHOCK TRAUMA CENTER Pharmacological thromboembolic prophylaxis in traumatic brain injuries Benjamin E., Recinos G., Aiolfi A., Inaba K., Demetriades D.et al. University of Southern California, USA J Trauma Acute Care Surg. 2017; 266: 463-469. • 20,417 TBI patients • Risk factors • Age > 65 • Hypotension on admission • >AIS • Time to VTE prophylaxis LMWH was independently associated with a lower risk of mortality and VTE regardless of timing
  23. 23. The Parkland Protocol’s Modified Berne-Norwood criteria predict two tiers of risk for traumatic brain injury progression Pastorek, RA< Cripps MW, Berstein IH, et al.et al. UT Southwestern / Parkland Memorial, USA J Neurotrauma 2014; 31: 1737-1743.
  24. 24. R ADAMS COWLEY SHOCK TRAUMA CENTER Spinal Cord Injury
  25. 25. R ADAMS COWLEY SHOCK TRAUMA CENTER Early chemoprophylaxis is associated with decreased venous thromboembolism risk…after traumatic spinal cord injury Chang R, Scerbo MH, Schmitt KM, et al..et al. University of Southern California, USA J Trauma Acute Care Surg 2017; 83(6): 1088-1094. • Early (n=260) vs. Late (n=241) LMWH • Aspirin also given to some patients • DVT • HR 0.37 (95% CI, 0.16-0.84) • Pulmonary Embolism • HR 0.20 (95% CI, 0.06-0.69) • Spinal hemorrhage in 4 patients • Aspirin not effective
  26. 26. R ADAMS COWLEY SHOCK TRAUMA CENTER Meta-analysis of heparin therapy for preventing venous thromboembolism in acute spinal cord injury Liu Y, Xu H, Liu F, et al.et al. Tianjin Medical University Heping District, China Int J Surg 2017; 43: 94-100.4. • Heparin better than nothing • LMWH = unfractionated • No difference in major bleeding
  27. 27. R ADAMS COWLEY SHOCK TRAUMA CENTER Other Modalities • Neuromuscular Stimulation • Better than nothing (for DVT) • Aspirin • Alternative agents • Fondaparinux Hajibandeh S. Cochrane Databases Sys Rev 2017; 11. Jong-Ping L. J Am Coll Surg 2009; 209.
  28. 28. R ADAMS COWLEY SHOCK TRAUMA CENTER IVC Filters
  29. 29. R ADAMS COWLEY SHOCK TRAUMA CENTER Mayo Clinic, Rochester, MN Prophylactic Inferior vena cava filters for trauma patients Cheryian J, Galvagno SM, Park M, et al..
  30. 30. R ADAMS COWLEY SHOCK TRAUMA CENTER Mayo Clinic, Rochester, MN Prophylactic Inferior vena cava filters for trauma patients Cheryian J, Galvagno SM, Park M, et al. .
  31. 31. Practice management guidelines for the prevention of venous thromboembolism in trauma patients: The EAST practice management guidelines work group Rogers FB, Cipolle MD, Velmahos G, Rozychi G, Luchette FA.et al. University of Vermont, USA J Trauma 2002; 53: 142-164. Class • High risk for VTE: spinal fractures and SCI • LMWH should be primary chemical prophylaxis for patients with ISS > 9 • Duplex US may be used alone for diagnosis in symptomatic patients Class II • Little evidence for UFH • LMWH should not be used in TBI patients with ICH • LMWH should not be used when epidural catheters are placed or removed Class III • Safety of UFH not established for high risk patients • AV foot pumps may be used as substitute for PCDs • PCDs may have some benefit • IVCF should only be placed in high risk patients who cannot receive anticoagulation or are immobilized for a prolonged period of time • Screening patients with serial duplex US may decrease incidence of PE and may be cost effective • Ascending venography should be used as a confirmatory study in patients with equivocal duplex US exams for DVT
  32. 32. R ADAMS COWLEY SHOCK TRAUMA CENTER CONCLUSIONS • Identify high risk patients • LMWH: drug of choice for trauma patients • aFXa levels: > 0.4 IU/mL? • Aspirin doesn’t work • Prophylactic IVC filters not recommended (conditional recommendation)
  33. 33. R ADAMS COWLEY SHOCK TRAUMA CENTER Thank you! sgalvagno@som.umaryland.edu
  34. 34. R ADAMS COWLEY SHOCK TRAUMA CENTER LMWH in TBI?? • Kwiatt, et al., 2012 • Retrospective multicenter trial • N=1,215 • 24 vs. 42%, P < 0.001, more hemorrhagic progression in LMWH gp • Limitations: Study gp more severely injured, LMWH gp smaller, variability in practice across centers, only 18% received LMWH, importance of radiographic progression vs. clinical, higher than previously reported hemorrhagic progression (14%, <2% in other studies)
  35. 35. R ADAMS COWLEY SHOCK TRAUMA CENTER Failure to prevent VTE! • Patterson et al., 2017 • Tibial fractures • SINGLE SURGICAL INTERVENTION • Meta-analysis • 5 studies, 1,181 patients • LMWH vs. placebo • No significant reduction! • Limitations: No dosing, no info on mobilization practices, weight bearing?
  36. 36. R ADAMS COWLEY SHOCK TRAUMA CENTER

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