PRESENTED BY:

JOY A. AWONIYI, PHARMD.PGY1 PHARMACIST PRACT ICE RES IDENT

MIAMI VA HEALTHCARE SYSTEM

Prevention of Venous Thromboembolism

2012 CHEST GUIDELINES REVIEW

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PRESENTATION OBJECTIVES

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

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VENOUS THROMBOEMBOLISM

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

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DVT PROPHYLAXIS

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

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RISK FACTORS

Strong Risk FactorsOdds Ratio > 10

• Hip or Leg Fracture• Hip or Knee

Replacement• Major General Surgery• Major Trauma• Spinal Cord Injury

Moderate Risk FactorsOdds Ratio 2-9

• Athroscopic Knee Surgery

• Central Venous Lines• Chemotherapy• CHF or Respiratory

Failure• Hormone Replacement

Therapy• Malignancy• Oral Contraceptive

Therapy• Paralytic Stroke• Pregnancy/ Postpartum• Previous VTE• Thrombophilia

Weak Risk FactorsOdds Ration <2

• Bed rest>3 days• Immobility due to

sitting• Increasing Age• Laparoscopic Surgery• Obesity• Pregnancy/ Antepartum• Varicose Veins

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Level of Risk Estimated DVT RiskSuggested

ThromboprophylaxisLow Minor surgery in mobile

patients Medical patients who are

fully mobile

<10%Early and aggressive

ambulation

Moderate Medical pts, bed rest or

sick Most general, open

gynecologic or urologic surgery patients

Moderate VTE + High bleeding risk

10%-40%

LMWH, LDUH BID/TID or Fondaparinux

Mechanical Thromboprophylaxis

High Risk Hip or knee

arthroplasty, Major Trauma, SCI

High VTE + High Bleeding risk

40% - 80%

LMWH

Mechanical Thromboprophylaxis

GENERAL THROMBOPROPHYLAXIS RECOMMENDATIONS

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ANTITHROMBOTIC THERAPY AND PREVENTION OF THROMBOSIS, 9 T H ED;

ACCP GUIDELINES

PREVENTION OF VTE IN NONSURGICAL PATIENTS

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CONSIDERATIONS

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

Advanced age

Previous VTE Cancer

Stroke with lower

extremity weakness

Congestive Heart

Failure

COPD Exacerbatio

nSepsis Bed Rest

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Recommended Recommended Against

Low-Molecular Weight Heparins, Low Dose Unfractionated Heparin or Fondaparinux for patients with high risk for thrombosis

Optimal use of mechanical thromboprophylaxis with GCS or IPC for patients with contraindications to anticoagulant thromboprophylaxis

The use of thromboprophylaxis beyond period of immobilization or acute hospital stay

The use of pharmacologic prophylaxis or mechanical prophylaxis in patients at low risk of thrombosis

Acutely Ill Hospitalized Medical Patients

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Critically-Ill Outpatients with Cancer

Low-Molecular Weight Heparins or Low dose Unfractionated Heparin is suggested

Mechanical prophylaxis with GCS or IPC for those who are at high risk for major bleeding until bleeding risk decreases

Recommend against routine prophylaxis with LMWH or LDUH if no additional risk factors Recommended for patients with

solid tumors who have additional risk factors

Recommend against use of vitamin K antagonists (Warfarin) for prophylaxis

Other Nonsurgical Patient Recommendations

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ANTITHROMBOTIC THERAPY AND PREVENTION OF THROMBOSIS, 9 T H ED;

ACCP GUIDELINES

PREVENTION OF VTE IN ORTHOPEDIC SURGERY PATIENTS

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Pharmacological Options

Additional Remarks

Low-Molecular Weight Heparin

FondaparinuxApixabanDabigatranRivaroxabanLow-Dose Unfractionated

HeparinWarfarin (INR 2-3)Aspirin

LMWH Preferred

Pharmacological therapy should be continued for a minimum of 10-14 days

Intermittent pneumatic compression devices should be used with patients with high bleeding risk Goal is to achieve 18h daily

compliance

Total Hip or Knee Arthroplasty

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Pharmacological Options

Additional Remarks

LMWH Preferred

Pharmacological therapy should be continued for a minimum of 10-14 days

Intermittent pneumatic compression devices should be used with patients with high bleeding risk Goal is to achieve 18h daily

compliance

Hip Fracture Surgery

Low-Molecular Weight Heparin

FondaparinuxApixabanDabigatranRivaroxabanLow-Dose

Unfractionated HeparinWarfarin (INR 2-3)Aspirin

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Additional Considerations

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

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PHAMACOLOGICAL THERAPY FOR VTE PROPHYLAXIS

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Unfractionated Heparin

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

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Enoxaparin (Lovenox®)

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%)

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Fondaparinux (Arixtra®)

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%)

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BLACK BOX WARNING!!!

“Epidural or spinal hematomas, which may

result in long-term paralysis, may occur in

patients who are anticoagulated with

LMWHs or heparinoids and are receiving

neuroaxial anesthesia or undergoing spinal

puncture”

Stop twice daily LMWH or UFH 8 – 12 hours prior to spinal puncture

Stop once daily LMWH 18 hours prior to spinal puncture

Monitor such patients frequently for neurological impairment

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Warfarin (Coumadin®)

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)

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Dabigatran (Pradaxa®)

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%)

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Rivaroxaban (Xarelto®)

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

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Apixaban (Eliquis®)

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

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IMPORTANT DRUG INTERACTIONS

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

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QUESTIONS?