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Trauma With an identifiable risk factor for thromboembolism
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Medical patients Acute myocardial infarction Ischemic stroke with impaired mobility General medical patients with clinical risk factors; especially patients with cancer, congestive heart failure, or severe pulmonary disease Cancer patients with indwelling central venous catheters
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Recommendations assembled from Geerts WH et al Prevention of venous thromboembolism Chest 2001 Jan;119(1 Suppl):132S 175S ADPW, adjusted-dose perioperative warfarin: begin 5 10 mg the day of or the day following surgery; adjust dose to INR 20 30; DVT, deep venous thrombosis; ES, elastic stockings; IPC, intermittent pneumatic compression; IVC, inferior vena cava; LDUH, low-dose unfractionated heparin: 5000 units subcutaneously every 8 12 hours starting 1 2 hours before surgery; LMWH, low-molecular-weight heparin See Table 9 24 for dosing regimens
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concurrently with heparin Warfarin affects hepatic synthesis of vitamin K dependent coagulant proteins It usually requires 5 7 days to become therapeutic; therefore, heparin is generally continued for 5 days Warfarin is safe if begun concurrently with heparin, initially at a dose of 25 10 mg/d The lower dose is preferred in elderly patients Maintenance therapy usually requires 2 15 mg/d Adequacy of therapy must be monitored by following the prothrombin time, most often adjusted for differences in reagents and reported as the international normalized ratio (INR) The target INR is 25, with the acceptable range from 20 to 30; below 20, there is an increased risk of thrombosis; above 40, there is an
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increased risk of hemorrhage Warfarin has interactions with many drugs Meticulous attention to medications is part of the routine management of every patient receiving warfarin Warfarin is a pregnancy category X medication, indicating known fetopathic and teratogenic effects When oral anticoagulation with warfarin is contraindicated, LMW heparin is a convenient alternative The optimal duration of anticoagulation therapy for venous thromboembolism is unknown There appears to be a protective benefit to continued anticoagulation in first-episode venous thromboembolism (twice the rate of recurrence in 6 weeks compared with 6 months of therapy) and recurrent disease (eightfold risk of recurrence in
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Table 9 20 Selected low-molecular-weight heparin and heparinoid regimens to prevent venous thromboembolism
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Risk Group General surgery, moderate risk Drug Dalteparin (Fragmin) Enoxaparin (Lovenox) Nadroparin (Fraxiparin) Tinzaparin (Innohep) General surgery, high risk Dalteparin (Fragmin) Danaparoid (Orgaran) Enoxaparin (Lovenox) Enoxaparin (Lovenox) Orthopedic surgery Dalteparin (Fragmin) Dalteparin (Fragmin) Danaparoid (Orgaran) Enoxaparin (Lovenox) Enoxaparin (Lovenox) Nadroparin (Fraxiparin) Tinzaparin (Innohep) Tinzaparin (Innohep) Major trauma Acute spinal cord injury Medical conditions Enoxaparin (Lovenox) Enoxaparin (Lovenox) Dalteparin (Fragmin) Danaparoid (Orgaran) Enoxaparin (Lovenox) Nadroparin (Fraxiparine)
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Subcutaneous Dose1 2500 units 20 mg 2850 units 3500 units 5000 units 750 units 40 mg 30 mg 5000 units 2500 units 750 units 30 mg 40 mg 38 units/kg 75 units/kg 4500 units 30 mg 30 mg 2500 units 750 units 40 mg 2850 units
Administration Regimen 1 2 h preop and qd postop 1 2 h preop and qd postop 2 4 h preop and qd postop 2 h preop and qd postop 8 12 preop and qd postop 1 4 h preop and q12 h postop 1 2 h preop and qd postop q12 h starting 8 12 h postop 8 12 h preop and qd starting 12 24 h postop 6 8 h postop then 5000 units qd 1 4 preop and q12 h postop q12 h starting 12 24 h postop qd starting 10 12 h preop 12 h preop, 12 h postop, and qd on postop days 1, 2, 3; then increase to 57 units/kg qd qd starting 12 24 h postop 12 h preop and qd postop q12h starting 12 36 h postinjury if hemostatically stable q12h qd q12h qd qd
Cost2 $1808/dose $2338/dose No price available: Not available in US $1411/dose $2934/dose No price available: Not available in US $3117/dose $2338/dose $2934/dose $1808/dose No price available: Not available in US $2338/dose $3117/dose No price available: Not available in US $1814/dose (60 kg pt) $1814/dose $2338/dose $2338/dose $1808/dose No price available: Not available in US $3117/dose No price available: Not available in US
Dose expressed in anti-Xa units; for enoxaparin, 1 mg = 100 anti-Xa units Average wholesale price (AWP, for AB-rated generic when available) for quantity listed Source: Red Book Update, Vol 26, No 3, March 2007 AWP may not accurately represent the actual pharmacy cost because wide contractual variations exist among institutions preop, preoperatively; postop, postoperatively; qd, once daily Modified and reproduced with permission, from Geerts WH et al Prevention of venous thromboembolism Chest 2001 Jan;119(1 Suppl):132S 175S
6 months compared with 4 years of therapy) These studies do not distinguish patients with reversible risk factors, such as surgery or transient immobility, from patients who have a nonreversible hypercoagulable state such as factor V Leiden, inhibitor deficiency, antiphospholipid syndrome, or malignancy A randomized controlled trial of low-dose warfarin (INR 15 20) versus no therapy following 6 months of standard therapy in patients with idiopathic DVT was stopped early The protective benefits of continued anticoagulation include fewer DVTs in addition to a trend toward lower mortality despite more hemorrhage in the warfarin group Risk reductions were consistent across groups with and without inherited thrombophilia For many patients, venous thrombosis is a recurrent disease, and continued therapy will result in a lower rate of recurrence at the cost of an increased risk of hemorrhage Therefore, the appropriate duration of therapy will
need to take into consideration potentially reversible risk factors, the individual s age, the likelihood and potential consequences of hemorrhage, and patient preferences for continued therapy It is reasonable to continue therapy for 6 months after a first episode when there is a reversible risk factor, 12 months after a first-episode idiopathic thrombus, and 6 12 months to indefinitely in patients with nonreversible risk factors or recurrent disease The optimal duration of therapy has not been established, but D-dimer testing has been suggested to have a role in identifying those who may benefit from continued anticoagulation after 3 months of therapy This is an area of active research The major complication of anticoagulation is hemorrhage Risk factors for hemorrhage include the intensity of the anticoagulant effect; the duration of therapy; concomitant administration of drugs such as aspirin that interfere with platelet function; and patient characteristics, particu-
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