DVT Prophylaxis of the Medical Patient

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DVT Prophylaxis of the Medical Patient

• Nicole Artz, MD
• David Lovinger, MD
• August, 2006

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Case

• Mr. 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 RA
• Barrel chested, b/l expiratory wheezes, prolonged
  expiratory phase,
• CXR hyperexpanded, no infiltrate, consolidation
  or edema.
• DX COPD Exacerbation

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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?

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Importance

• What 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 US

Sandler DA JR Soc Med 1989 82, Lindblad B Br Med
J 1991 302.
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Prevalence in Medical Pts

• 3 large-scale randomized studies (5500 medically
  ill patients)
• DVT identified w/ screening studies
• Patients receiving no prophylaxis
• VTE 11-15 of patients
• Proximal DVT- 4-5 of patients
• Rates similar to moderate-high risk general
  surgery patients.

Samana, MM NEJM, 1999 Leizorovicz, A Circulation
2004 Cohen, AT J Thromb Haemost, 2003.
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Prevalence
ACCP Guidelines, Chest. 2005.
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Prevalence
Pendleton, R. Amer J. Hematology 2005.
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Prevalence

• 3 out of 4 hospital pts dying from PE have NOT
  had recent surgery
• 2.5 of medical patients immobilized with
  multiple clinical problems suffer fatal PE.
• National DVT Free Registry
• 60 of patients dx with acute DVT were in the
  peri-hospitalization period
• 60 of cases were in non-surgical patients!

Haas, S. Seminars in Thrombosis and Haemostasis,
2002 Goldhaber, SZ Am J Cardiol 2004.
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Risk Factors

• Heterogeneous 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.

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Risk Factors

• Acute 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, ½ of these
  were proximal leg vein thromboses)
• Central venous catheters (25-46 VTE risk)
• Malignancy

Haas, S. Seminars in Thrombosis and Hemostasis,
2002 Pendleton, Amer J Hematology, 2005.
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Abstracted from Pendleton, R. Amer J Hemat 2005.
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Current Rates of Prophylaxis

• IMPROVE study
• Ongoing multinational observational cohort study
  in acutely ill medical patients
• Only 34 of potentially at risk patients are
  receiving any prophylaxis!
• Only ½ of patients who would have met criteria
  used for MEDENOX study received any VTE
  prophylaxis.

Anderson FA, IMPROVE Blood 2003.
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Current Rates of Prophylaxis

• University of Utah
• Pre and post intervention study
• Pts stratified into high and low risk groups
  based on risk factors
• Pre-intervention group
• 75 of patients admitted to medical service were
  high risk
• Only 43 received prophylaxis of any type.

Stinnett, J American Journal of Hematology 2005.
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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 prophylaxis
• 29 of pts had 1 major or 2 minor risk fxs, no
  contraindications, and yet had NO prophylaxis.

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What Should We Use for Prophylaxis?

• Mechanical compression devices? (compression
  stockings, IPC devices)
• Unfractionated heparin BID?
• Unfractionated heparin TID?
• Low Molecular Weight Heparin? (Enoxaparin,
  Daltaparin)
• Fondaparinux?

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What Do We Know About Prophylaxis?

• What are the most common regimens in the US?
• UFH BID, mechanical compression devices
• Which regimens have the least data to support
  them?
• UFH BID, mechanical compression devices
• What are characteristics of the ideal prophylaxis
  regimen?
• Effective
• Safe
• Cost-effective

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Key VTE Prevention Trials
MEDENOX study included 20 mg enoxaparin arm
which was no more effective than placebo.
Pendleton, R. Amer J. Hemat. 2005
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(No Transcript)
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Remember that MEDENOX found enoxaparin 20 mg no
more effective than placebo, therefore calling
into doubt efficacy of bid heparin dosing.
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Complications of Prophylaxis

• Bleeding
• Major bleeding rates no different from placebo in
  major trials w/ enoxaparin, dalteparin, and
  fondaparinux (rates 0.2-1.7)
• HIT
• Develops 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 Hematol 2005.
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Special Populations

• Obesity
• Renal Insufficiency
• Elderly

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Obesity

• Anti 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 gt32.
• BMI gt32 VTE rate 32 vs 17 for BMI lt32. (Samama,
  MM, 1995)
• Non-randomized study in bariatric surg pts-
  suggested decreased DVT rates w/ enoxaparin 40 mg
  bid vs 30 mg bid. (Scholten, DJ, 2002)
• No data to guide adjustments in therapy.
• Options include
• Use standard dose
• Add mechanical measures
• Empiric dose adjustments

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Renal Insufficiency

• Delayed renal clearance of LMWHs and
  Fondaparinux problematic.
• Lack of outcomes based data.
• FDA approved enoxaparin 30 mg qd for pts with
  creat clearance lt30 ml/min based on
  pharmacokinetic data alone.
• Additional options include UFH, mechanical
  devices.

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Patients with HIT

• Avoid UFH or LMWHs.
• ? Fondaparinux? Trials ongoing.
• Mechanical compression devices /- duplex US
  surveillance.

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Elderly Patients

• Mahe 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 Hemat 2005.
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Take Home Points

• The 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 daily
• Daltaparin 5000 IU SC daily
• Fondaparinux 2.5 mg sc daily
• UFH 5000 units SC every 8hrs
• Must use clinical judgement for unique patient
  groups with lack of data.