Thromboembolism

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

Disclosures
• United States Air Force Reserve
• UpToDate® Author
• Department of Defense Funding

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

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.

Pathophysiology
and
Risk Factors

Pathophysiology
Semin Nucl Med. 2001; 31(2).
Crit Care Clin. 2011; 27(4).
Circulation. 2003; 107(23 Suppl 1).

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 ??

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

Wells Criteria
Wells PS. N Engl J Med 2003; 349.
Modi S. World J Emerg Surg 2016; 11.

Wells Score in Trauma
Modi S. World J Emerg Surg 2016; 11.

Greenfield Risk Assessment Profile (RAP)
Greenfield LJ. J Trauma 1997.
≥10

Pharmaceutical Prophylaxis

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

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)

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

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

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%

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

Reversal?
Clinical Practice Guideline on Anticoagulant Dosing and Management. American
Society of Hematology / American College of Chest Physicians, 8th Edition. 2011.

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

TBI

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

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.

Spinal Cord Injury

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

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

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.

IVC Filters

Mayo Clinic, Rochester, MN
Prophylactic Inferior vena cava filters for trauma patients
Cheryian J, Galvagno SM, Park M, et al..

Mayo Clinic, Rochester, MN
Prophylactic Inferior vena cava filters for trauma patients
Cheryian J, Galvagno SM, Park M, et al. .

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

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)

Thank you!
sgalvagno@som.umaryland.edu

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)

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?

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