This document provides an overview of venous thromboembolism (VTE) prevention guidelines from the 2012 CHEST guidelines. It discusses VTE risk factors and general thromboprophylaxis recommendations. For medical patients, it recommends low-molecular weight heparins, fondaparinux, or low-dose unfractionated heparin for high-risk patients. For orthopedic surgeries, it recommends low-molecular weight heparins, fondaparinux, or other anticoagulants for a minimum of 10-14 days along with mechanical prophylaxis for high bleeding risk patients. It also reviews medications used for VTE prevention and important drug interactions.

1. Prevention of Venous
Thromboembolism
2012 CHEST GUIDELINES REVIEW
PRESENTED BY:
J O Y A . AW O N I Y I , P H A R M D .
PGY1 PHARMACIST PRACTICE RESIDENT
MIAMI VA HEALTHCARE SYSTEM

2. PRESENTATION OBJECTIVES
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 Provide a brief background regarding venous thromboembolism (VTE)
 Identify the risk factors for developing VTE
 Review the general principles for thromboprophylaxis
 Review CHEST Guideline VTE prophylaxis recommendations for
 Medical Conditions
 Orthopedic Surgery
 Review old and new suggested medications to be used for VTE
prevention
 Describe potential drug-interactions related to patients who may be
admitted to psychiatric services

3. VENOUS THROMBOEMBOLISM
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 Result of clot formation in
venous circulation
 Manifests as deep vein
thrombosis (DVT) or
pulmonary embolism (PE)
 Develops as a result of three
primary components known
as Virchow’s triad
 Venous Stasis
 Vascular Injury
 Hypercoagulability

4. DVT PROPHYLAXIS
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 Incidence of DVT in the hospital is 10-40% per month
for medical or general surgical patients and 40-60%
following major orthopedic surgeries
 Consequences of unprevented VTE:
 Symptomatic DVT or PE
 Fatal PE
 Increased spending for investigation symptomatic patients
 Increased risk of recurrence
 Chronic post-thrombotic syndrome
 DVT prophylaxis, has a desirable benefit-to-risk ratio

5. RISK FACTORS
Strong Risk Factors Moderate Risk Factors Weak Risk Factors
Odds Ratio > 10 Odds Ratio 2-9 Odds Ration <2
• Hip or Leg Fracture • Athroscopic Knee Surgery • Bed rest>3 days
• Hip or Knee Replacement • Central Venous Lines • Immobility due to sitting
• Major General Surgery • Chemotherapy • Increasing Age
• Major Trauma • CHF or Respiratory Failure • Laparoscopic Surgery
• Spinal Cord Injury • Hormone Replacement • Obesity
Therapy • Pregnancy/ Antepartum
• Malignancy • Varicose Veins
• Oral Contraceptive Therapy
• Paralytic Stroke
• Pregnancy/ Postpartum
• Previous VTE
• Thrombophilia
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6. GENERAL THROMBOPROPHYLAXIS
RECOMMENDATIONS
Level of Risk Estimated DVT Risk Suggested Thromboprophylaxis
Low
 Minor surgery in mobile
patients <10% Early and aggressive ambulation
 Medical patients who are fully
mobile
Moderate
 Medical pts, bed rest or sick LMWH, LDUH BID/TID or
 Most general, open gynecologic Fondaparinux
or urologic surgery patients
10%-40%
 Moderate VTE + High bleeding Mechanical
risk Thromboprophylaxis
High Risk
 Hip or knee arthroplasty,
Major Trauma, SCI LMWH
40% - 80%
 High VTE + High Bleeding risk Mechanical Thromboprophylaxis
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7. PREVENTION OF VTE IN
NONSURGICAL PATIENTS
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ANTITHROMBOTIC THERAPY AND
P R E V E N T I O N O F T H R O M B O S I S , 9 TH E D ; A C C P
GUIDELINES

8. CONSIDERATIONS
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 50 – 70% of symptomatic thromboembolic events and
70 – 80% of fatal PEs occur in non-surgical patients
 Additional risk factors for VTE in medical patients
Stroke with
Advanced age Previous VTE Cancer lower extremity
weakness
Congestive COPD
Sepsis Bed Rest
Heart Failure Exacerbation

9. Acutely Ill Hospitalized Medical Patients
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Recommended Recommended Against
 Low-Molecular Weight  The use of thromboprophylaxis
Heparins, Low Dose beyond period of
Unfractionated Heparin or immobilization or acute
Fondaparinux for patients hospital stay
with high risk for thrombosis
 Optimal use of mechanical
thromboprophylaxis with GCS  The use of pharmacologic
or IPC for patients with prophylaxis or mechanical
contraindications to prophylaxis in patients at low
anticoagulant
thromboprophylaxis risk of thrombosis

10. Other Nonsurgical Patient Recommendations
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Critically-Ill Outpatients with Cancer
 Recommend against routine
 Low-Molecular Weight
prophylaxis with LMWH or
Heparins or Low dose
LDUH if no additional risk
Unfractionated Heparin factors
is suggested  Recommended for patients with solid
tumors who have additional risk
factors
 Mechanical prophylaxis
with GCS or IPC for
those who are at high  Recommend against use of
risk for major bleeding vitamin K antagonists
until bleeding risk (Warfarin) for prophylaxis
decreases

11. PREVENTION OF VTE IN
ORTHOPEDIC SURGERY PATIENTS
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ANTITHROMBOTIC THERAPY AND
P R E V E N T I O N O F T H R O M B O S I S , 9 TH E D ; A C C P
GUIDELINES

12. Total Hip or Knee Arthroplasty
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Pharmacological Options Additional Remarks
 Low-Molecular Weight  LMWH Preferred
Heparin
 Fondaparinux  Pharmacological therapy
 Apixaban should be continued for a
minimum of 10-14 days
 Dabigatran
 Rivaroxaban  Intermittent pneumatic
 Low-Dose Unfractionated compression devices should
Heparin be used with patients with
 Warfarin (INR 2-3) high bleeding risk
 Goal is to achieve 18h daily
 Aspirin compliance

13. Hip Fracture Surgery
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Pharmacological Options Additional Remarks
 Low-Molecular Weight  LMWH Preferred
Heparin
 Fondaparinux  Pharmacological therapy
should be continued for a
 Apixaban minimum of 10-14 days
 Dabigatran
 Rivaroxaban  Intermittent pneumatic
 Low-Dose compression devices should
Unfractionated Heparin be used with patients with
high bleeding risk
 Warfarin (INR 2-3)  Goal is to achieve 18h daily
 Aspirin compliance

14. Additional Considerations
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 Low-Molecular Weight Heparins (Enoxaparin)
 Start 12 or more hours preoperatively OR 12 hours or more
postoperatively
 Guidelines suggest to extend prophylaxis in the outpatient
period for up to 35 days from the date of surgery
 Guidelines Suggest using dual prophylaxis with an
antithrombotic agent AND an IPCD during hospital stay
 Therapy is not recommended in patients undergoing knee
arthroscopy

15. PHAMACOLOGICAL THERAPY
FOR VTE PROPHYLAXIS
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16. Unfractionated Heparin
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 VTE Prophylaxis Dosing
 5000 Units subcutaneously every 8 – 12
hours
 Knee or hip replacement: give 2 hours
before surgery, resume at full dose after
surgery for at least 7 days
 Renal adjustment not required
 Adverse Effects
 Thrombocytopenia (up to 30%) – monitor
platelets
 Hemorrhage (5-10%), Increased ALT/AST

17. Enoxaparin (Lovenox®)
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 DVT Prophylaxis Dosing
 Knee or Hip Replacement: 30 mg subcutaneous every 12
hours
 Medical Patients: 40mg subcutaneously every 24 hours
 Dose Reduction is required in patients with CrCl
less than 30 mL/min
 Knee or Hip replacement: 30 mg every 24 hours
 Medical patients: 30mg every 24 hours
 Adverse Effects
 Hemorrhage (7%), AST/ALT elevation (6%), Fever (5%), Local
Site reactions (2-5%)

18. Fondaparinux (Arixtra®)
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 VTE Prophylaxis Dosing (Patients >50kg)
 2.5mg subcutaneously every 24 hours
 Knee or Hip Replacement: Give 6-8 hours AFTER surgery
 No official dose adjustment recommendations
 CrCl 20 – 50 mL/min: 1.5 mg every 24 hours has been used
 Clearance is reduced 25-40% in patients with CrCl between
30 and 80 mL/min
 CONTRAINDICATED if CrCl is less than 30mL/min
 Adverse Effects
 Anemia (20%), Fever (14%), Nausea (11%), Rash (7.5%)

19. BLACK BOX WARNING!!!
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 Stop twice daily LMWH or
UFH 8 – 12 hours prior to
“Epidural or spinal
spinal puncture
hematomas, which may
result in long-term paralysis,
may occur in patients who  Stop once daily LMWH 18
are anticoagulated with hours prior to spinal
LMWHs or heparinoids and puncture
are receiving neuroaxial
anesthesia or undergoing  Monitor such patients
spinal puncture” frequently for
neurological impairment

20. 20

21. Warfarin (Coumadin®)
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 INR target of 2.5 (Range between 2 – 3)
 Dose adjust based on INR Results
 Reversal with Vitamin K
 Many drug and food interactions
 Metabolized primarily by CYP2c9 and CYP3A4
 Works by inhibiting the formation of Vitamin-K dependent clotting
factors
 Adverse Effects:
 Alopecia, hemorrhage, tissue necrosis (rare)

22. Dabigatran (Pradaxa®)
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 Not FDA Approved for VTE prophylaxis
 150mg by mouth twice daily
 75mg by mouth if CrCl is less than 30 mL/min
 Surgical considerations
 Discontinue 1-2 days prior to an invasive or elective surgical procedure
 Discontinue 3-5 days prior to procedure if CrCl is less than 50
 Reinitiate ASAP after procedures
 Not reversible
 Adverse Effects
 GI effects (6.1%), Bleeding (16.6%)

23. Rivaroxaban (Xarelto®)
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 VTE Prophylaxis Dosing
 Knee or hip replacement surgery: 10mg by mouth daily
 Begin 6 – 10 hours after surgery
 Continue for 12 days after knee, 35 days after hip
 Secondary DVT/PE Prophylaxis: 2omg by mouth daily
 DISCONTINUE at least 24 hours prior to procedure
 Avoid if CrCl is less than 30 mL/min
 Adverse Effects
 Bleeding (5.8%), Epidural hematoma
 Carries same Black box Warning as LMWHs

24. Apixaban (Eliquis®)
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 New reversible and selective active site inhibitor of factor Xa
 Dosing (European Medicines Agency-Approved dosing)
 Knee replacement surgery: 2.5mg by mouth daily
 Begin 12 – 24 hours after surgery
 Continue 10 – 14 days
 Hip replacement surgery: 2.5mg by mouth twice daily
 Begin 12 – 24 hours after surgery
 Continue 32 – 38 days
 DISCONTINUE 24 - 48 hours prior to elective or invasive surgery
procedures
 Dose adjusted for body weight, age, renal impairment, and
CYP3A4 inhibitors

25. IMPORTANT DRUG INTERACTIONS
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 Medications that increase bleeding risk
 SSRI’s and SNRIs
 Medications for pain (NSAIDs, Willow Bark)
 Kava Kava may impair blood clotting due to effects on the liver
 Medications that alter metabolism
 Barbiturates, such as phenobarbital, may induce metabolism of
heparins, decreasing effect
 Carbamazepine/oxcarbamezapine and St. John’s Wort induce
metabolism of warfarin and apixaban by inducing 3A4 and 2C9
 Bad habits
 Smoking induces metabolism
 Alcohol increasing bleeding risk

26. QUESTIONS?
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