Enoxaparin Sodium

Anticoagulant; an LMWH.1 2 3 4

Thromboprophylaxis in General/Abdominal Surgery

Prevention of postoperative DVT, which may lead to PE, in patients undergoing general/abdominal surgery who are at risk for thromboembolic complications.1

The American College of Chest Physicians (ACCP) recommends pharmacologic (e.g., LMWH) and/or nonpharmacologic/mechanical (e.g., intermittent pneumatic compression) methods of thromboprophylaxis in patients undergoing general surgery, including abdominal, GI, gynecologic, and urologic surgery, according to the patient’s risk of thromboembolism and bleeding.1002 In general, pharmacologic prophylaxis is recommended in patients with high (and possibly moderate) risk of venous thromboembolism who do not have a high risk of bleeding, while mechanical methods are suggested in patients who require thromboprophylaxis but have a high risk of bleeding.1002

If pharmacologic prophylaxis is used in patients undergoing general surgery, ACCP states that an LMWH or low-dose heparin (“heparin” referring throughout this monograph to unfractionated heparin) is preferred.1002

Because risk of venous thromboembolism is particularly high in patients undergoing abdominal or pelvic surgery for cancer, extended (4 weeks) prophylaxis with an LMWH is recommended in such patients.1002

ACCP states that the recommendations for use of antithrombotic agents in general surgery patients can be applied to patients undergoing bariatric, vascular, and plastic/reconstructive surgery.1002

Thromboprophylaxis in Hip-Replacement, Knee-Replacement, or Hip-Fracture Surgery

Prevention of postoperative DVT, which may lead to PE, in patients undergoing hip-replacement surgery.1 2 3 5 6 7 20 21 22 27 34 35 36 37 38 1003

Prevention of DVT and/or PE in patients undergoing knee-replacement surgery.1 20 22 1003

Also has been used for thromboprophylaxis in patients undergoing hip-fracture surgery†.1003

ACCP recommends routine thromboprophylaxis (with a pharmacologic and/or mechanical method) in all patients undergoing major orthopedic surgery because of high risk of postoperative venous thromboembolism; continue thromboprophylaxis for at least 10–14 days, and possibly for up to 35 days after surgery†.1003

Several antithrombotic agents (e.g., LMWHs, fondaparinux, low-dose heparin, warfarin, aspirin) recommended by ACCP for pharmacologic prophylaxis during major orthopedic surgery.1003 When selecting an appropriate thromboprophylaxis regimen, consider factors such as efficacy, safety, logistics, and compliance.1003

Medical Conditions Predisposing to Thromboembolism

Prevention of DVT, which may lead to PE, in patients with severely restricted mobility during acute illness.1 2 3 5 6 7 20 21 22 27 34 35 36 37 1001

In general, pharmacologic thromboprophylaxis recommended only in patients considered to be at high risk of venous thromboembolism.1001

ACCP recommends anticoagulant prophylaxis (e.g., LMWH) in acutely ill, hospitalized medical patients at increased risk of thrombosis who are not actively bleeding and do not have an increased risk of bleeding.1001 Continued thromboprophylaxis suggested for 6–21 days until full mobility is restored or hospital discharge, whichever comes first.1001

Use of LMWHs also suggested by ACCP for pharmacologic thromboprophylaxis in critically ill patients (e.g., those in an intensive care unit [ICU]) who are not actively bleeding and do not have risk factors for bleeding.1001

Risk of venous thromboembolism is particularly high in patients with cancer.1001 Use of LMWH prophylaxis suggested by ACCP in cancer outpatients with solid tumors who have additional risk factors for thromboembolism, provided risk of bleeding is low.1001

Treatment and Secondary Prevention of Acute DVT and/or PE

Inpatient treatment of acute DVT with or without PE when administered in conjunction with warfarin.1 28 1005

Outpatient treatment of acute DVT without PE when administered in conjunction with warfarin.1 28 1005

Recommended by ACCP as an appropriate choice of anticoagulant for initial treatment of acute proximal DVT and/or PE.1005

LMWHs or fondaparinux generally preferred over heparin for initial treatment of acute venous thromboembolism; however, heparin may be preferred in patients with renal impairment.1005 IV heparin also may be preferred over LMWH in patients with PE in whom thrombolytic therapy is being considered or if there is concern about adequate sub-Q absorption.1005

For long-term anticoagulant therapy (secondary prevention), warfarin generally preferred in patients without cancer; however, in patients with cancer, ACCP suggests use of an LMWH because of a possible reduced response to warfarin in such patients.1005

Continue anticoagulant therapy for at least 3 months, and possibly longer depending on individual clinical situation.1005

Unstable Angina or Non-ST-Segment Elevation MI (NSTEMI)

Reduction in the risk of acute cardiac ischemic events (death, MI) in patients with unstable angina or NSTEMI when administered concurrently with aspirin and/or other standard therapy (e.g., nitrates, β-adrenergic blockers, clopidogrel, platelet glycoprotein [GP] IIb/IIIa-receptor inhibitors).1 40 41 42 43 48 53 146 991

Initiate anticoagulant therapy as soon as possible after hospital admission.991

In patients undergoing an invasive management strategy, the American College of Cardiology (ACC), the American Heart Association (AHA), and the American College of Cardiology Foundation (ACCF) recommend use of enoxaparin, heparin, bivalirudin, or fondaparinux for anticoagulant therapy.991

In patients undergoing a conservative management strategy, recommended anticoagulants include an LMWH, heparin, or fondaparinux; fondaparinux is preferred in patients with increased risk of bleeding.991

Also used in patients with unstable angina/NSTEMI undergoing PCI to prevent thrombus formation during the procedure.994

Acute ST-Segment Elevation MI (STEMI)

Used for the treatment of patients with acute STEMI receiving thrombolysis and being managed medically or with PCI.1 162 164 165 994

Some experts state use of an LMWH also may be reasonable in patients with STEMI who are not receiving thrombolytic therapy, provided no contraindications to anticoagulation exist.106

Experts recommend use of an LMWH in combination with thrombolytic therapy and/or antiplatelet agents (e.g., aspirin, P2Y12 receptor antagonist, GP IIb/IIIa-receptor inhibitor) during and after successful coronary artery reperfusion for the prevention of ischemic complications of acute STEMI (e.g., death, reinfarction, stroke).106

Adjunctive use of an LMWH in patients with acute STEMI associated with improvement in short-term clinical outcomes (e.g., death, reinfarction, recurrent ischemia) with generally similar rates of bleeding complications compared with adjunctive heparin or placebo.106 129 130 131 132 133

LMWHs may be preferred over heparin in patients with acute STEMI who have preserved renal function (Scr ≤2.5 mg/dL in men or ≤2 mg/dL in women).106

Also used for prevention of systemic embolism following acute STEMI in high-risk patients (e.g., patients with large or anterior MI, atrial fibrillation, previous embolus, documented left ventricular thrombus, cardiogenic shock).106

Also used in patients with STEMI undergoing PCI to prevent thrombus formation during the procedure.1 994

Treatment of Superficial Vein Thrombosis

LMWHs also have been used for treatment of spontaneous superficial vein thrombosis (superficial thrombophlebitis)†; ACCP suggests use of prophylactic dosages for 45 days in patients with superficial vein thrombosis of ≥5 cm in length.1005

Thromboprophylaxis in Cardiac Surgery

Mechanical methods of prophylaxis generally recommended in patients undergoing cardiac surgery; however, ACCP states that an LMWH may be considered for thromboprophylaxis in cardiac surgery patients† with a complicated postoperative course.1002

Thromboprophylaxis in Thoracic Surgery

Pharmacologic thromboprophylaxis (e.g., LMWH) recommended by ACCP in patients undergoing thoracic surgery† who are at high risk of venous thromboembolism, provided risk of bleeding is low.1002

Thromboprophylaxis in Neurosurgery

LMWHs have been used for prevention of venous thromboembolism in patients undergoing craniotomy†; however, benefits of such prophylaxis may be outweighed by possible increased risk of intracranial hemorrhage.1002 ACCP states that LMWH prophylaxis may be considered in patients at very high risk of thromboembolism (e.g., those undergoing craniotomy for malignant disease) once adequate hemostasis established and risk of bleeding decreases.1002

Thromboprophylaxis with LMWHs also may be considered in high-risk patients undergoing spinal surgery† (e.g., those with malignancy or those undergoing surgery with a combined anterior-posterior approach) once adequate hemostasis established and risk of bleeding decreases.1002

Thromboprophylaxis in Trauma

May be used for thromboprophylaxis in patients with major trauma†.1002 For major trauma patients at high risk of venous thromboembolism, including those with acute spinal cord injury, traumatic brain injury, or spinal surgery for trauma, ACCP suggests use of both a pharmacologic and mechanical method of prophylaxis, unless contraindications exist.1002

Treatment of Renal Vein Thrombosis

Although use of anticoagulant therapy for renal vein thrombosis† (most common cause of spontaneous venous thromboembolism in neonates) is controversial, LMWHs are suggested by ACCP as a possible treatment option in selected neonates.1013

Thromboprophylaxis in Acute Ischemic Stroke

Heparin anticoagulants (i.e., LMWH or heparin) have been used for thromboprophylaxis in selected patients with acute ischemic stroke†; those with additional risk factors for venous thromboembolism are more likely to benefit from such prophylaxis.1009

ACCP suggests thromboprophylaxis with an LMWH, sub-Q heparin, or intermittent pneumatic compression in patients with acute ischemic stroke† and restricted mobility; LMWH is preferred over heparin.1009

Prophylactic-dose heparin (heparin or an LMWH) usually initiated within 48 hours of onset of stroke and continued throughout hospital stay until patient regains mobility; do not administer within the first 24 hours after thrombolytic therapy.1009

LMWHs also recommended by ACCP as an option for initial management of acute arterial ischemic stroke in children† until dissection and embolic causes have been excluded.1013 If arterial ischemic stroke is associated with dissection or a cardioembolic origin, continued anticoagulant therapy suggested.1013

In children with acute arterial ischemic stroke secondary to non-Moyamoya vasculopathy†, ACCP recommends ongoing antithrombotic therapy (e.g., with an LMWH) for 3 months.1013

LMWHs may be considered in neonates with a first episode of arterial ischemic stroke associated with a documented cardioembolic source†.1013

Thromboembolism During Pregnancy

Used during pregnancy for prevention and treatment of venous thromboembolism†, and for prevention and treatment of systemic embolism associated with mechanical heart valves.138 996 1012 (See Treatment and Prevention of Thromboembolism During Pregnancy under Dosage and Administration.)

Also has been used in combination with low-dose aspirin for prevention of recurrent pregnancy loss in women with antiphospholipid antibody (APLA) syndrome†.1012

LMWHs (rather than heparin or warfarin) are recommended by ACCP for prevention and treatment of thromboembolism during pregnancy†.1012

In pregnant women with an acute venous thromboembolic event†, ACCP recommends an LMWH for initial treatment and secondary prevention throughout the remainder of the pregnancy.1012 To prevent recurrence of postpartum anticoagulation (for ≥6 weeks and for a total duration of ≥3 months) is suggested.1012

In general, thromboprophylaxis (e.g., with an LMWH) is suggested during the antepartum period only in pregnant women who have a history of thromboembolism† and are considered to be at moderate to high risk of recurrent events (e.g., those with a single episode of unprovoked venous thromboembolism, pregnancy- or estrogen-related venous thromboembolism, history of multiple unprovoked events).1012

Postpartum thromboprophylaxis† for 6 weeks is suggested in all pregnant women with a prior venous thromboembolic event; an LMWH (in prophylactic or intermediate dosages) or warfarin (INR 2–3) may be used for such prophylaxis.1012

Hereditary thrombophilias substantially increase risk of pregnancy-related venous thromboembolism; a family history of venous thromboembolism further increases risk.1012 ACCP suggests antepartum and postpartum prophylaxis with an LMWH in some pregnant women with high-risk hereditary thrombophilias (e.g., homozygous genetic mutations for factor V Leiden or prothrombin G20210A) who have not experienced a prior venous thromboembolic event, but have a family history of thromboembolism†.1012

An LMWH has been used in combination with low-dose aspirin for prevention of pregnancy loss in women with antiphospholipid antibodies (APLA) syndrome and recurrent (3 or more) pregnancy loss†.138 1012

Discontinue LMWH therapy ≥24 hours prior to induction of labor or cesarean section (or expected time of neuraxial anesthesia) to avoid an unwanted anticoagulant effect on fetus.1012

Cardioversion of Atrial Fibrillation/Flutter

LMWHs have been used for prevention of stroke and systemic embolism in patients with atrial fibrillation or atrial flutter undergoing electrical or pharmacologic cardioversion†.999 1007

As an alternative to prolonged anticoagulation (e.g., usually with warfarin) prior to cardioversion in patients with atrial fibrillation lasting >48 hours or of unknown duration, LMWHs (in therapeutic dosages) may be used at the time of transesophageal echocardiography (TEE), followed by cardioversion within 24 hours if no thrombus is detected.999 1007

In patients with atrial fibrillation of short duration (e.g., ≤48 hours), LMWHs (in therapeutic dosages) may be used at presentation, followed by immediate cardioversion.1007

In patients with hemodynamic instability who require urgent cardioversion, ACCP suggests administration of a parenteral anticoagulant (in therapeutic dosages) prior to cardioversion, if possible; however, such anticoagulant therapy must not delay any emergency intervention.999 1007

After successful cardioversion to sinus rhythm, all patients should receive therapeutic anticoagulation for ≥4 weeks.999 1007

Thromboprophylaxis in Patients with Prosthetic Heart Valves

Used during conversion to maintenance therapy with warfarin to reduce the incidence of thromboembolism in patients with prosthetic mechanical heart valves†.64 83 87 90 93 97 98 1008

ACCP suggests bridging anticoagulation (an LMWH in either prophylactic or therapeutic dosages or IV heparin in prophylactic dosages) during the early postoperative period after insertion of a mechanical heart valve in patients without bleeding risk, until an adequate response to warfarin is obtained.1008

Also may be used for bridging anticoagulation in patients with a mechanical heart valve in whom therapy with warfarin must be temporarily discontinued (e.g., those undergoing major surgery).1004

Has been used for thromboprophylaxis in pregnant women with prosthetic mechanical heart valves†.138 1012 (See Thromboembolism During Pregnancy under Uses.)

Venous Thromboembolism in Pediatric Patients

An LMWH has been used for treatment and secondary prevention of venous thromboembolism in pediatric patients†; venous thromboembolism usually occurs secondary to an identifiable risk factor (e.g., presence of central venous access device) in such patients.1013

Recommendations regarding use of antithrombotic therapy in children generally based on extrapolation from adult guidelines.1013

ACCP recommends an LMWH or heparin for both initial and ongoing treatment of venous thromboembolism in children.1013 Potential advantages of an LMWH over heparin include reduced need for monitoring, lack of drug or dietary interactions, reduced risk of heparin-induced thrombocytopenia (HIT), and possible reduced risk of osteoporosis.1013

In children with central venous catheter-related thromboembolism, ACCP recommends removal of catheter if no longer functioning or required; at least 3–5 days of therapeutic anticoagulation is suggested prior to removal.1013 If such catheters must remain in place, ACCP suggests anticoagulant therapy until catheter is removed.1013

Treatment of Cerebral Venous Sinus Thrombosis

May be used for the treatment of acute cerebral venous sinus (sinovenous) thrombosis† in adults.1009 Once patient is stable, may convert to coumarin anticoagulant therapy.138 1009

Reasonable to use full-dose LMWH rather than heparin for treatment of acute cerebral venous sinus thrombosis during pregnancy.1017 Prophylaxis with an LMWH during pregnancy and the postpartum period is reasonable in women with history of cerebral venous sinus thrombosis.1017

Recommended by ACCP as an option for initial and follow-up anticoagulation in children with cerebral venous sinus thrombosis† without substantial intracranial hemorrhage.1013 Also has been suggested for use in children with substantial hemorrhage.1013

LMWHs also suggested by ACCP as a treatment option for neonates with cerebral sinovenous thrombosis†.1013

Perioperative Antithrombotic Prophylaxis

ACCP suggests use of an LMWH or IV heparin during temporary interruption of warfarin therapy (bridging anticoagulation†) in selected patients with venous thromboembolism, atrial fibrillation, or mechanical prosthetic heart valves undergoing surgery or other invasive procedures; use and type of bridging anticoagulation depend on patient's risk of developing thromboembolism without warfarin therapy.1004

In general, bridging anticoagulation is suggested in such patients who are considered to be at particularly high risk of venous thromboembolism without oral anticoagulant therapy.1004

• Has less effect than heparin on thrombin at a given level of anti-factor Xa activity.1 2 17

• Prolongs some global clotting function tests (i.e., thrombin time, activated partial thromboplastin time [aPTT]) by up to 1.8 times the control value.1 At a recommended dosage in a large clinical trial, the aPTT was ≤45 seconds in most treated patients.1

• Importance of advising patients who have had neuraxial anesthesia or spinal puncture to monitor for manifestations of spinal or epidural hematoma (e.g., tingling or numbness in lower limbs, muscle weakness), particularly if they are receiving concomitant NSAIAs, platelet-aggregation inhibitors (e.g., clopidogrel), or other anticoagulants; importance of immediately contacting a clinician if any of these symptoms occur.1

• If therapy is to continue after hospital discharge, importance of instructing patient on proper injection technique of enoxaparin.1

• Importance of informing patients that they may bruise and/or bleed more easily and that a longer than normal time may be required to stop bleeding when taking enoxaparin.1 Importance of patients reporting any unusual bleeding, bruising, or signs of thrombocytopenia (e.g., dark red spots under skin) to clinician.1

• Importance of patients informing clinicians (including dentists) that they are receiving enoxaparin therapy before scheduling any invasive procedures.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing patients of other important precautionary information. (See Cautions.)

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