 Ministry of Health
http://newzealand.govt.nz/
©Copyright
Published:
28/11/2011
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DVT Prophylaxis in Trauma
Peter Clark
Outline DVT Prophylaxis In Critically Ill and Trauma
Peter T. Clark
FACEM, FJFICM, FANZCA
Intensive Care Units Westmead Hospital & Westmead Private Hospital
Careflight Medical Retrieval Service
Deputy Director NSW Medical Retrieval Unit
Director NSW Institute Trauma & Injury Management
Why is it Important
High prevalence of VTE
* Most hospitalised patients have risk factors
* DVT is common in many patient groups
* Hospital acquired DVT and PE are usually clinically silent.
* Difficult to predict
* Screening is usually ineffective
Why is it important?
* Adverse consequences of VTE
* Fatal Pulmonary Embolus
* Costs of investigating and treating symptomatic patients
* Increased future risk of recurrent VTE
* Chronic post thrombotic syndrome
Risk Factors in ICU
Absolute risk of DVT
Risk factors and OR for VTE among Trauma patients
Why is it important?
* Efficacy and Effectiveness of Thromboprophylaxis
* Highly efficacious in preventing DVT
* DVT prevention prevents VTE
* Prophylaxis is cost-effective
* Prophylaxis often omitted
What are the options?
* Mechanical Devices
* Elastic stockings
* Compression devices - Pneumatic (IPD), Sequential pneumatic (SCD), Foot Pumps
* Chemical Prophylaxis
* Heparins
* Oral anticoagulants???
* Newer agents?
What are the options?
* Currently available data is unequivocally in favour of Heparin - LDUH or LMWH.
* No evidence for aspirin or other platelet agents
* Some evidence for mechanical devices, especially as adjuncts
Mechanical Devices
Effects of compression methods
of thromboprophylaxis on DVT
Heparin Mechanisms
* Anti thrombin activation
* Occurs when the penta-saccharide chain randomly distributed along the UH or
LMWH chain binds to anti thrombin.
* Anti thrombin then under goes a conformational change that accelerates
interaction between anti thrombin, factor X a and thrombin
Unfractionated Heparin
* Heterogenous polysaccharide chains
* MW 3,000-30,000 Daltons
* 1/3 dose contains penta-saccharide sequence
* Anti X a: anti II a ratio =1:1
* Non-specific binding to macrophages, platelets, and endothelial cells makes
anticoagulation difficult to predict
Low molecular weight heparin
* Derived from UH molecules
* MW 1000-10,000 daltons
* Penta-saccharide sequence present on roughly 15-25% of LMWH chains
* Predominant anti Xa antagonism
* Anti Xa: anti II a ratio 4:1-5:1
* Less binding to macrophages and endothelial cells-predictable, reliable, safe
Advantages of LMWH over UH
* Decreased "heparin resistance"
* Pharmaco-kinetics of UH are influenced by its bindings to plasma protein,
endothelial cell surfaces, macrophages, and other acute phase reactants
* LMWH has decreased binding to non anticoagulant-related plasma proteins
Advantages of LMWH over UH
* No need for laboratory monitoring
* when given on a weight-adjusted basis, the LMWH anticoagulant response is
predictable and reproducible
* Higher bioavailability - 90% vs 30%
* Longer plasma half-life
* 4 to 6 hours vs. 0.5 to 1 hour
* Renal (slower) vs. Hepatic clearance
Advantages of LMWH over UH
* Less inhibition of platelet function
* potentially less bleeding risk, but not shown in clinical use
* Lower incidence of thrombocytopenia and thrombosis (HIT syndrome)
* less interaction with platelet factor 4
* fewer heparin-dependent IgG antibodies
WHICH HEPARIN?
HOW MUCH?
HOW OFTEN?
Unfractionated Heparin
* Primary agent over many years.
* Data primarily from surgical patients
* 60-70% relative risk reduction in both DVT/PE
* Data supporting UH use in medical patients are more difficult to
interpret.
Unfractionated heparin
* Earliest study 30 years back
* Patients with MI, HF and unspecified medical problems
* DVT rates 2.6% and 22.5% in Heparin and placebo groups.
* Similar results in a larger study in 192 patients older than 40 years with
pulmonary disease
Low molecular weight heparins
* ENOXAPARIN
* DALTEPARIN
* FRAXIPARIN etc.
ENOXAPARIN
* First trial- 270 patients; 60mg s/c bd vs placebo
* Significant reduction of frequency of DVT
* More injection site hematomas.
* No clinically significant bleeding.
Enoxaparin in Medicine Study Group (EMSG)
* 5000 U UH q 12 h vs Enoxaparin 20 mg s/c bd in 442 elderly ICU patients
* No difference in DVT rates diagnosed by RFUT
Prophylaxis in Medical Patients with Enoxaparin (MEDENOX)
* Targets: Risk of VTE
Safety and efficacy of 20mg vs. 40mg bd of Enoxaparin
* No difference in incidence of DVT/VTE between placebo and 20mg bd Enoxaparin
* 63% risk reduction with 40mg bd dose.
* Benefit maintained for 110 days.
* No major bleeding/thrombocytopenia.
* No data on 40mg bd Enoxaparin vs. UH
Thrombo-embolism prophylaxis in Internal Medicine with Enoxaparin (PRIME) Group
* Multi-center, double blind, RCT 885 pts- 40mg bd Enoxaparin vs. 5000U UH q 8h.
* No statistical difference in incidence of VTE.
* No difference in major bleeding tendencies
* Fewer injection site haematomas with Enoxaparin
Thrombo-embolism prevention in cardiopulmonary diseases with Enoxaparin (PRINCE)
* Enoxaparin 40mg bd vs UH 5000 U q8h- 665 patients.
* No difference in DVT prevention rates
* More bleeding in UH group
* Better risk reduction with Enoxaparin in those with CHF.
Prospective Evaluation of Dalteparin Efficacy for Prevention of VTE in
Immobilised patients (PREVENT)
* 3706, moderate risk hospitalised patients Dalteparin 5000 U vs. Placebo once
daily for 14 days
* Assessed for DVT at 21 days
* 2.77% vs 4.96% in favour of Dalteparin
* 45% risk reduction with Dalteparin
* No data in exclusively ICU patients
Prophylaxis recommendations in critically ill patients
Principles of DVT prophylaxis in critically ill patients
* Daily review - change prn
* No interruption for Sx or procedures unless risk of bleeding is high.
* Routine screening for asymptomatic patients not recommended if prophylaxis has
been adequate.
* Periodic audits.
DVT Prophylaxis Recommendations
* 5.1 Trauma
* All trauma patients receive thromboprophylaxis, if possible (Grade 1A).
* Unless contraindicated, use LMWH starting as soon as it is considered safe to
do so (Grade 1A).
* Recommend against the use of vena cava filters as primary prophylaxis in
trauma patients (Grade 1C).
* Recommend continuation of prophylaxis through the completion of inpatient
rehab (Grade 1C+), and suggest continued prophylaxis after discharge with LMWH
or VKA in patients with impaired mobility (Grade 2C).
Initial prophylaxis consideration
To summarize......
* All ICU & Trauma patients have a combination of risk factors for VTE.
* Balanced assessment and decision making crucial.
* LMWH preferred in those with multiple risk factors vs. risk bleeding
* Adherence to guidelines and regular audits needed for better results.
PROphylaxis for ThromboEmbolism in Critical Care Trial (PROTECT)
* Effect of LMWH vs. UH on primary outcome of DVT diagnosed by USG
* LMWH vs. UH on secondary outcomes of PE, HIT and Bleeding.
* Expected enrolment 3600
* Expected completion June 2009.
What's new?
Synthetic oligo-saccharides
* Result of breakthrough in polysaccharide chemistry.
* Fondaparinux-selective inhibitor of factor Xa.
* Approved for use in orthopaedic surgery.
* Also found to be beneficial in ACS and in VTE.
* Efficacy at least as good as Enoxaparin; better safety profile.
Arixtra for Thromboembolism Prevention in a Medical Indications Study (ARTEMIS)
* 849 acutely ill medical patients bedridden for >4 days
* Multinational, double blind
* 2.5mg Fondparinux vs placebo once daily.
* Venography at 6 and 14 days
* 5.6 vs 10.6% with OR 49.5% for DVT
* No PTE in fondparinux group vs 1.2% in placebo group
* Similar bleeding rates
Properties of conventional anticoagulants
Direct Thrombin Inhibitors (DTI)
* Parenteral
Hirudin
Bivalirudin
Argatroban
* Oral
Ximelagatran- studied in DVT
Effects of compression methods
of thromboprophylaxis on DVT
Effects of compression methods
of thromboprophylaxis on PE
Why Is Prophylaxis Omitted?
* Lack of awareness
* Diversion of attention
* Concerns regarding safety of regimens
* Neurosurgical - Brain, Spinal
* More daily injections
* Cost
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