DVT Prophylaxis of DVT Prophylaxis of the Medical Patientthe Medical Patient

Nicole Artz, MDNicole Artz, MD

David Lovinger, MDDavid Lovinger, MD

August, 2006August, 2006

CaseCase

Mr. Smith- 71 y/o man admitted to general medicine Mr. Smith- 71 y/o man admitted to general medicine ward service.ward service.– HPI: gradually increased sob over 3 days assoc. with new HPI: gradually increased sob over 3 days assoc. with new

productive cough, rhinorrhea, and fatigue.productive cough, rhinorrhea, and fatigue.

– PMH: COPD, CHF (LVEF 35%), CRI (creat 2.5)PMH: COPD, CHF (LVEF 35%), CRI (creat 2.5)

– ROS: No h/o DVT/PE.ROS: No h/o DVT/PE.

– PE: VSS with SPO2 93% on RAPE: VSS with SPO2 93% on RA Barrel chested, b/l expiratory wheezes, prolonged expiratory phase,Barrel chested, b/l expiratory wheezes, prolonged expiratory phase,

CXR: hyperexpanded, no infiltrate, consolidation or edema. CXR: hyperexpanded, no infiltrate, consolidation or edema.

– DX: COPD ExacerbationDX: COPD Exacerbation

Does this man need DVT Does this man need DVT prophylaxis?prophylaxis?

Why worry about VTE in inpatients?Why worry about VTE in inpatients?

What is the prevalence of DVT/PE in What is the prevalence of DVT/PE in hospitalized medical patients?hospitalized medical patients?

Is this man at risk for venous Is this man at risk for venous thromboembolism?thromboembolism?

What are effective methods of prophylaxis?What are effective methods of prophylaxis?

What adjustments need to be made based on What adjustments need to be made based on his history of renal insufficiency?his history of renal insufficiency?

ImportanceImportance

What % of all hospital related deaths due to What % of all hospital related deaths due to fatal PE?fatal PE?

– 7-10%7-10%

What % of these pts had NO premorbid What % of these pts had NO premorbid symptoms?symptoms?

– 70-90%70-90%

200,000 potentially preventable annual deaths 200,000 potentially preventable annual deaths due to PE in the USdue to PE in the US

Sandler DA JR Soc Med 1989; 82, Lindblad B Br Med J 1991; 302.

Prevalence in Medical Prevalence in Medical PtsPts

3 large-scale randomized studies (5500 3 large-scale randomized studies (5500 medically ill patients) medically ill patients) – DVT identified w/ screening studiesDVT identified w/ screening studies

Patients receiving no prophylaxis:Patients receiving no prophylaxis:– VTE 11-15% of patientsVTE 11-15% of patients

– Proximal DVT- 4-5% of patientsProximal DVT- 4-5% of patients

Rates Rates similar to moderate-high risk general surgery similar to moderate-high risk general surgery patients.patients.

Samana, MM NEJM, 1999; Leizorovicz, A Circulation 2004; Cohen, AT J Thromb Haemost, Samana, MM NEJM, 1999; Leizorovicz, A Circulation 2004; Cohen, AT J Thromb Haemost, 2003.2003.

PrevalencePrevalence

ACCP Guidelines, Chest. 2005.

PrevalencePrevalence

Pendleton, R. Amer J. Hematology 2005.

PrevalencePrevalence 3 out of 4 hospital pts dying from PE have 3 out of 4 hospital pts dying from PE have

NOT had recent surgery…NOT had recent surgery… 2.5% of medical patients immobilized with 2.5% of medical patients immobilized with

multiple clinical problems suffer fatal PE.multiple clinical problems suffer fatal PE. National DVT Free RegistryNational DVT Free Registry

– 60% of patients dx with acute DVT were in the 60% of patients dx with acute DVT were in the peri-hospitalization periodperi-hospitalization period

– 60% of cases were in non-surgical patients!60% of cases were in non-surgical patients!

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

Risk FactorsRisk Factors

Heterogeneous population!Heterogeneous population! Need to consider:Need to consider:

– Acute medical condition (MI, pneumonia, etc.)Acute medical condition (MI, pneumonia, etc.)

– Underlying risk factors (h/o VTE, estrogen use, Underlying risk factors (h/o VTE, estrogen use, etc.)etc.)

– Medical interventions (central venous catheters, Medical interventions (central venous catheters, chemotherapy, etc.)chemotherapy, etc.)

Relative contribution of various risk factors Relative contribution of various risk factors still being defined.still being defined.

Risk FactorsRisk Factors Acute medical conditions well accepted as high risk:Acute medical conditions well accepted as high risk:

– MI (24% VTE risk)MI (24% VTE risk)

– Decompensated CHF (40% VTE risk)Decompensated CHF (40% VTE risk)

– Acute Stroke (30-75% VTE risk) Acute Stroke (30-75% VTE risk)

– Spinal Cord Injury (up to 100%)Spinal Cord Injury (up to 100%)

– MICU admission (13-33*% VTE risk, *½ of these were MICU admission (13-33*% VTE risk, *½ of these were proximal leg vein thromboses)proximal leg vein thromboses)

– Central venous catheters (25-46% VTE risk)Central venous catheters (25-46% VTE risk)

– MalignancyMalignancy

Haas, S. Seminars in Thrombosis and Hemostasis, 2002; Pendleton, Amer J Hematology, Haas, S. Seminars in Thrombosis and Hemostasis, 2002; Pendleton, Amer J Hematology, 2005.2005.

Abstracted from Pendleton, R. Amer J Hemat 2005.

Current Rates of Current Rates of ProphylaxisProphylaxis

IMPROVE studyIMPROVE study

– Ongoing multinational observational cohort study Ongoing multinational observational cohort study in acutely ill medical patientsin acutely ill medical patients

– Only 34% of potentially at risk patients are Only 34% of potentially at risk patients are receiving any prophylaxis!receiving any prophylaxis! Only ½ of patients who would have met criteria used Only ½ of patients who would have met criteria used

for MEDENOX study received any VTE prophylaxis.for MEDENOX study received any VTE prophylaxis.

Anderson FA, IMPROVE; Blood 2003.

Current Rates of Current Rates of ProphylaxisProphylaxis

University of UtahUniversity of Utah

– Pre and post intervention studyPre and post intervention study

– Pts stratified into high and low risk groups based Pts stratified into high and low risk groups based on risk factorson risk factors

– Pre-intervention groupPre-intervention group 75% of patients admitted to medical service were high 75% of patients admitted to medical service were high

riskrisk

Only 43% received prophylaxis of any type.Only 43% received prophylaxis of any type.

Stinnett, J American Journal of Hematology 2005.

How Are We Doing at UCH?How Are We Doing at UCH?

Retrospective chart review by Linda Nahlik, Pharm-Retrospective chart review by Linda Nahlik, Pharm-D, 2005.D, 2005.

98 pts admitted to gen med service NOT on 98 pts admitted to gen med service NOT on therapeutic anticoagulation.therapeutic anticoagulation.

– 20% of pts had a contraindication to prophylaxis (active 20% of pts had a contraindication to prophylaxis (active bleeding)bleeding)

– Only 4% had no risk factors for prophylaxisOnly 4% had no risk factors for prophylaxis

– 29%29% of pts had 1 major or 2 minor risk fxs, no of pts had 1 major or 2 minor risk fxs, no contraindications, and yet had contraindications, and yet had NO prophylaxisNO prophylaxis..

What Should We Use for What Should We Use for Prophylaxis?Prophylaxis?

Mechanical compression devices? Mechanical compression devices? (compression stockings, IPC devices)(compression stockings, IPC devices)

Unfractionated heparin BID?Unfractionated heparin BID?

Unfractionated heparin TID?Unfractionated heparin TID?

Low Molecular Weight Heparin? (Enoxaparin, Low Molecular Weight Heparin? (Enoxaparin, Daltaparin)Daltaparin)

Fondaparinux?Fondaparinux?

What are the most common regimens in the US? What are the most common regimens in the US? – UFH BID, mechanical compression devicesUFH BID, mechanical compression devices

Which regimens have the least data to support them?Which regimens have the least data to support them?– UFH BID, mechanical compression devicesUFH BID, mechanical compression devices

What are characteristics of the ideal prophylaxis What are characteristics of the ideal prophylaxis regimen?regimen?– EffectiveEffective

– SafeSafe

– Cost-effectiveCost-effective

What Do We Know About What Do We Know About Prophylaxis?Prophylaxis?

Key VTE Prevention Key VTE Prevention TrialsTrials

Pendleton, 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 dosing.

Complications of Complications of ProphylaxisProphylaxis

BleedingBleeding– Major bleeding rates no different from placebo in major Major bleeding rates no different from placebo in major

trials w/ enoxaparin, dalteparin, and fondaparinux (rates trials w/ enoxaparin, dalteparin, and fondaparinux (rates 0.2-1.7%)0.2-1.7%)

HITHIT– Develops in 1.4% of medically ill pts exposed to Develops in 1.4% of medically ill pts exposed to

preventive doses of UFH.preventive doses of UFH.

– Potentially catastrophic- thrombosis rates as high as 60%.Potentially catastrophic- thrombosis rates as high as 60%.

– LMWH’s 8-10X’s less likely to cause HIT.LMWH’s 8-10X’s less likely to cause HIT.

– Fondaparinux does not cause HIT.Fondaparinux does not cause HIT.Girolami, B. Blood 2003; Warkentin TE, Br J Haematol 2003. Pendleton, R. Am J Hematol 2005.

Special PopulationsSpecial Populations

ObesityObesity

Renal InsufficiencyRenal Insufficiency

ElderlyElderly

ObesityObesity Anti Xa levels with fixed dose LMWH regimens correlate negatively with Anti Xa levels with fixed dose LMWH regimens correlate negatively with

BMI in critically ill patients. BMI in critically ill patients. (Priglinger U, 2003)(Priglinger U, 2003)

Standard prophylactic regimens twice as likely to fail in orthopedic pts Standard prophylactic regimens twice as likely to fail in orthopedic pts with BMI >32.with BMI >32.– BMI >32 VTE rate 32% vs 17% for BMI <32. BMI >32 VTE rate 32% vs 17% for BMI <32. (Samama, MM, 1995)(Samama, MM, 1995)

Non-randomized study in bariatric surg pts- suggested decreased DVT Non-randomized study in bariatric surg pts- suggested decreased DVT rates w/ enoxaparin 40 mg bid vs 30 mg bid. rates w/ enoxaparin 40 mg bid vs 30 mg bid. (Scholten, DJ, 2002)(Scholten, DJ, 2002)

No data to guide adjustments in therapy.No data to guide adjustments in therapy.

Options include:Options include:

– Use standard doseUse standard dose

– Add mechanical measuresAdd mechanical measures

– Empiric dose adjustmentsEmpiric dose adjustments

Renal InsufficiencyRenal Insufficiency

Delayed renal clearance of LMWH’s and Delayed renal clearance of LMWH’s and Fondaparinux problematic.Fondaparinux problematic.

Lack of outcomes based data.Lack of outcomes based data.

FDA approved enoxaparin 30 mg qd for pts FDA approved enoxaparin 30 mg qd for pts with creat clearance <30 ml/min based on with creat clearance <30 ml/min based on pharmacokinetic data alone.pharmacokinetic data alone.

Additional options include UFH, mechanical Additional options include UFH, mechanical devices.devices.

Patients with HITPatients with HIT

Avoid UFH or LMWH’s.Avoid UFH or LMWH’s.

? Fondaparinux? Trials ongoing. ? Fondaparinux? Trials ongoing.

Mechanical compression devices +/- duplex Mechanical compression devices +/- duplex US surveillance.US surveillance.

Elderly PatientsElderly Patients Mahe et al. monitored anti-Xa levels in 68 Mahe et al. monitored anti-Xa levels in 68

consecutive hospitalized elderly patients (mean age consecutive hospitalized elderly patients (mean age 82) receiving enoxaparin for 82) receiving enoxaparin for prophylaxisprophylaxis..

By day 2 over half had levels in the By day 2 over half had levels in the therapeutic therapeutic range.range.

Lack of safety data with use of UFH as well.Lack of safety data with use of UFH as well.

Lack of outcomes data.Lack of outcomes data.– Consider empiric dose reduction or use of mechanical Consider empiric dose reduction or use of mechanical

devices alone for elderly patients with low body weight devices alone for elderly patients with low body weight and/or marginal creatinine clearance (30-60 ml/min).and/or marginal creatinine clearance (30-60 ml/min).

Mahe, I, Pathophysiol Haemost Thromb 2002., Pendleton R, Am J Hemat 2005.

Take Home PointsTake Home Points The majority of hospitalized medical patients are at increased The majority of hospitalized medical patients are at increased

risk for VTE.risk for VTE.

In the absence of contraindicatons, prophylaxis should be In the absence of contraindicatons, prophylaxis should be provided for patients provided for patients based on assessment of risksbased on assessment of risks..

Safe and Effective preventive regimens include:Safe and Effective preventive regimens include:– Enoxaparin 40 mg SC dailyEnoxaparin 40 mg SC daily

– Daltaparin 5000 IU SC dailyDaltaparin 5000 IU SC daily

– Fondaparinux 2.5 mg sc dailyFondaparinux 2.5 mg sc daily

– UFH 5000 units SC every 8hrsUFH 5000 units SC every 8hrs

*Must use clinical judgement for unique patient groups with lack of data.*Must use clinical judgement for unique patient groups with lack of data.