DVT Prophylaxis of the Medical PatientNicole Artz, MDDavid
Lovinger, MDAugust, 2006
CaseMr. Smith- 71 y/o man admitted to general medicine ward
service.HPI: gradually increased sob over 3 days assoc. with new
productive cough, rhinorrhea, and fatigue.PMH: COPD, CHF (LVEF
35%), CRI (creat 2.5)ROS: No h/o DVT/PE.PE: VSS with SPO2 93% on
RABarrel chested, b/l expiratory wheezes, prolonged expiratory
phase,CXR: hyperexpanded, no infiltrate, consolidation or edema.
DX: COPD Exacerbation
Does this man need DVT prophylaxis?Why worry about VTE in
inpatients?What is the prevalence of DVT/PE in hospitalized medical
patients?Is this man at risk for venous thromboembolism?What are
effective methods of prophylaxis?What adjustments need to be made
based on his history of renal insufficiency?
ImportanceWhat % of all hospital related deaths due to fatal
PE?7-10%What % of these pts had NO premorbid symptoms?70-90%200,000
potentially preventable annual deaths due to PE in the USSandler DA
JR Soc Med 1989; 82, Lindblad B Br Med J 1991; 302.
Prevalence in Medical Pts3 large-scale randomized studies (5500
medically ill patients) DVT identified w/ screening studiesPatients
receiving no prophylaxis:VTE 11-15% of patientsProximal DVT- 4-5%
of patientsRates similar to moderate-high risk general surgery
patients.Samana, MM NEJM, 1999; Leizorovicz, A Circulation 2004;
Cohen, AT J Thromb Haemost, 2003.
PrevalenceACCP Guidelines, Chest. 2005.
PrevalencePendleton, R. Amer J. Hematology 2005.
Prevalence3 out of 4 hospital pts dying from PE have NOT had
recent surgery2.5% of medical patients immobilized with multiple
clinical problems suffer fatal PE.National DVT Free Registry60% of
patients dx with acute DVT were in the peri-hospitalization
period60% of cases were in non-surgical patients!
Haas, S. Seminars in Thrombosis and Haemostasis, 2002;
Goldhaber, SZ Am J Cardiol 2004.
Risk FactorsHeterogeneous population!Need to consider:Acute
medical condition (MI, pneumonia, etc.)Underlying risk factors (h/o
VTE, estrogen use, etc.)Medical interventions (central venous
catheters, chemotherapy, etc.)Relative contribution of various risk
factors still being defined.
Risk FactorsAcute medical conditions well accepted as high
risk:MI (24% VTE risk)Decompensated CHF (40% VTE risk)Acute Stroke
(30-75% VTE risk) Spinal Cord Injury (up to 100%)MICU admission
(13-33*% VTE risk, * of these were proximal leg vein
thromboses)Central venous catheters (25-46% VTE
risk)MalignancyHaas, S. Seminars in Thrombosis and Hemostasis,
2002; Pendleton, Amer J Hematology, 2005.
Abstracted from Pendleton, R. Amer J Hemat 2005.
Current Rates of ProphylaxisIMPROVE studyOngoing multinational
observational cohort study in acutely ill medical patientsOnly 34%
of potentially at risk patients are receiving any prophylaxis!Only
of patients who would have met criteria used for MEDENOX study
received any VTE prophylaxis.
Anderson FA, IMPROVE; Blood 2003.
Current Rates of ProphylaxisUniversity of UtahPre and post
intervention studyPts stratified into high and low risk groups
based on risk factorsPre-intervention group75% of patients admitted
to medical service were high riskOnly 43% received prophylaxis of
any type.Stinnett, J American Journal of Hematology 2005.
How Are We Doing at UCH?Retrospective chart review by Linda
Nahlik, Pharm-D, 2005.98 pts admitted to gen med service NOT on
therapeutic anticoagulation.20% of pts had a contraindication to
prophylaxis (active bleeding)Only 4% had no risk factors for
prophylaxis29% of pts had 1 major or 2 minor risk fxs, no
contraindications, and yet had NO prophylaxis.
What Should We Use for Prophylaxis?Mechanical compression
devices? (compression stockings, IPC devices)Unfractionated heparin
BID?Unfractionated heparin TID?Low Molecular Weight Heparin?
What Do We Know About Prophylaxis?What are the most common
regimens in the US? UFH BID, mechanical compression devicesWhich
regimens have the least data to support them?UFH BID, mechanical
compression devicesWhat are characteristics of the ideal
Key VTE Prevention TrialsPendleton, R. Amer J. Hemat.
2005**MEDENOX study included 20 mg enoxaparin arm which was no more
effective than placebo.
*Remember that MEDENOX found enoxaparin 20 mg no more effective
than placebo, therefore calling into doubt efficacy of bid heparin
Complications of ProphylaxisBleedingMajor bleeding rates no
different from placebo in major trials w/ enoxaparin, dalteparin,
and fondaparinux (rates 0.2-1.7%)HITDevelops in 1.4% of medically
ill pts exposed to preventive doses of UFH.Potentially
catastrophic- thrombosis rates as high as 60%.LMWHs 8-10Xs less
likely to cause HIT.Fondaparinux does not cause HIT.Girolami, B.
Blood 2003; Warkentin TE, Br J Haematol 2003. Pendleton, R. Am J
Special PopulationsObesityRenal InsufficiencyElderly
- ObesityAnti Xa levels with fixed dose LMWH regimens correlate
negatively with BMI in critically ill patients. (Priglinger U,
2003)Standard prophylactic regimens twice as likely to fail in
orthopedic pts with BMI >32.BMI >32 VTE rate 32% vs 17% for
- Renal InsufficiencyDelayed renal clearance of LMWHs and
Fondaparinux problematic.Lack of outcomes based data.FDA approved
enoxaparin 30 mg qd for pts with creat clearance
Patients with HITAvoid UFH or LMWHs.? Fondaparinux? Trials
ongoing. Mechanical compression devices +/- duplex US
Elderly PatientsMahe et al. monitored anti-Xa levels in 68
consecutive hospitalized elderly patients (mean age 82) receiving
enoxaparin for prophylaxis.By day 2 over half had levels in the
therapeutic range.Lack of safety data with use of UFH as well.Lack
of outcomes data.Consider empiric dose reduction or use of
mechanical devices alone for elderly patients with low body weight
and/or marginal creatinine clearance (30-60 ml/min).
Mahe, I, Pathophysiol Haemost Thromb 2002., Pendleton R, Am J
Take Home PointsThe majority of hospitalized medical patients
are at increased risk for VTE.In the absence of contraindicatons,
prophylaxis should be provided for patients based on assessment of
risks.Safe and Effective preventive regimens include:Enoxaparin 40
mg SC dailyDaltaparin 5000 IU SC dailyFondaparinux 2.5 mg sc
dailyUFH 5000 units SC every 8hrs*Must use clinical judgement for
unique patient groups with lack of data.