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Author: Wai Hong Wilson Tang, MD, Assistant Professor of Medicine, Section of Heart Failure and Cardiac Transplantation Medicine, Cleveland Clinic Foundation

Wai Hong Wilson Tang is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Diabetes Association, American Heart Association, and International Society for Heart and Lung Transplantation

Editors: Marc D Basson, MD, PhD, MBA, Professor, Department of Surgery, Wayne State University School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Donna Leco Mercado, MD, Director of Medical Consultation, Department of Internal Medicine, Baystate Medical Center; Assistant Professor, Tufts University School of Medicine; Paolo Zamboni, MD, Professor of Surgery, Chief of Day Surgery Unit, Chair of Vascular Diseases Center, University of Ferrara, Italy; William A Schwer, MD, Professor, Department of Family Medicine, Rush Medical College; Chairman, Department of Family Medicine, Rush-Presbyterian-St Luke's Medical Center

Author and Editor Disclosure

Synonyms and related keywords: perioperative deep venous thrombosis prophylaxis, prevention of venous thromboembolism, pulmonary embolism, PE, Virchow triad, stasis, hypercoagulability, intimal injury, venous pooling, anesthesia effects, coagulopathy, vasodilation, adjusted-dose subcutaneous heparin, ADH, low-dose unfractionated heparin, LDH, low molecular weight heparin, LMWH, anticoagulant, anticoagulation, anticoagulation therapy, DVT prevention, PE prevention, deep vein thrombosis prevention, deep venous thrombosis prevention, pulmonary embolism prevention, PE prophylaxis, DVT prophylaxis, deep vein thrombosis prophylaxis, deep venous thrombosis prophylaxis

Deep venous thrombosis (DVT) is a common and highly preventable perioperative complication. A pooled analysis of 54 studies involving 4310 patients suggests that at least 25 of 100 patients who underwent surgical intervention may experience DVT. The risk of DVT following elective neurosurgery (24%) is comparable to that following general surgery, but the DVT risk nearly doubles after elective total hip replacement (45-57%), total knee replacement (40-84%), or hip fracture surgery (36-60%).

The true prevalence of perioperative pulmonary embolism (PE) is unknown, and it varies according to the type of surgery, the use and type of prophylaxis, and the mode of diagnosis. Estimates indicate that without prophylaxis, fatal PE occurs in 0.1-0.8% of patients undergoing elective general surgery, 2-3% of those undergoing elective hip replacement, and up to 4-7% of those undergoing surgery for a fractured hip. Despite overwhelming evidence for the effectiveness of regimens for DVT prophylaxis, the concern over bleeding risks often dissuades physicians to comply with guidelines.



The Virchow triad (ie, stasis, hypercoagulability, intimal injury) is often used to explain the development of perioperative DVT. The first component of the triad is stasis, which is a result of the venous pooling that accompanies both the supine positioning and the effects of anesthesia. The second component, hypercoagulability, occurs as a consequence of decreased clearance of the procoagulant factors, with or without underlying coagulopathies. The third component, intimal injury, results from excessive vasodilation caused by vasoactive amines and anesthesia. The combined influence of these factors promotes the development of venous thrombi in low-flow areas (eg, subadjacent to the venous valves or adjacent to foci of intimal disruption). The propagation of thrombus leads to the development of overt DVT.



Risk factors for developing short-term (30-day) postoperative risk for DVT have been examined in a prospective cohort of 21,903 consecutive surgical patients:

  • Age older than 50 years
  • History of varicose veins
  • History of myocardial infarction
  • History of cancer
  • History of atrial fibrillation
  • History of ischemic stroke
  • History of diabetes mellitus

Other additional factors included previous DVT, heart failure, obesity, paralysis, or the presence of an inhibitor deficiency state. Among inherited conditions, factor V Leiden accounts for 40-50% of cases; other causes include prothrombin gene mutation, protein S deficiency, protein C deficiency, and antithrombin deficiency.



Goals of therapy

Perioperative (or primary) prophylactic therapy in patients with risk factors for DVT or PE requires prevention of both the occurrence of DVT or PE and the consequences of DVT or PE. The 2 main strategies are (1) nonpharmacologic interventions and (2) pharmacologic interventions. Based on published data, the Seventh American College of Chest Physicians (ACCP) Consensus Conference on Antithrombotic Therapy recommend that patients are classified as having low, moderate, high, and very high risks for the development of DVT or PE and that the prophylactic regimens are used according to this risk stratification, as described in the Table.

Classification of Risk Levels*

Risk levelSurgical ParametersThromboembolic Event, %
Calf Vein ThrombosisProximal Vein ThrombosisClinical PEFatal PE
LowUncomplicated minor surgery in patients younger than 40 years with no clinical risk factors; require general anesthesia less than 30 minutes20.40.20.002
ModerateAny surgery in patients aged 40-60 years with no additional risk factors
Major surgery in patients younger than 40 years with no additional risk factors; require general anesthesia longer than 30 minutes
Minor surgery in patients with risk factors
10-202-41-20.1-0.4
HighMajor surgery in patients older than 60 years without additional risk factors or patients aged 40-60 years with additional risk factors
Patients with myocardial infarction (MI)
Medical patients with risk factors
20-404-82-40.4-1
HighestMajor surgery in patients older than 40 years with prior venous thromboembolism, malignant disease, or hypercoagulable state
Patients with elective major lower extremity orthopedic surgery, hip fracture, stroke, multiple trauma, or spinal cord injury
40-8010-204-100.2-5

*Adapted from 2004 ACCP Consensus Conference

Absolute contraindications to antithrombotic or anticoagulant therapy include active bleeding, severe bleeding diathesis or platelet count less than 20,000/µL, neurosurgery, ocular surgery, or intracranial bleeding within the past 10 days. Relative contraindications include mild-to-moderate bleeding diathesis or platelet count 20,000-100,000/µL, brain metastases or recent major trauma, major abdominal surgery within past 2 days, gastrointestinal or genitourinary bleeding within past 14 days, infective endocarditis, or malignant hypertension.

Low-dose unfractionated heparin (LDUH) is usually given at 5,000 U, administered SC q8h (high risk) to SC q12h (moderate risk), usually starting 1-2 h preoperatively. Adjusted dose heparin is no longer recommended.

Low–molecular-weight heparin is widely used in the perioperative setting for DVT prophylaxis. Overall, heparin and LMWH are equivalent in preventing DVT, although LMWH has greater bioavailability, longer duration of anticoagulant effect in fixed doses, and little requirement for laboratory monitoring (thus is more cost-effective). Preoperative prophylaxis with LMWH leads to a lower frequency of bleeding complications (0.9% vs 3.5%) and a lower incidence of DVT (10% vs 15.3%) than with postoperative unfractionated heparin. Postoperative use of LMWH (up to 2-3 wk after hospital discharge) results in a lower frequency of DVT; however, use LMWH with caution in patients with spinal punctures or epidural catheters because of the risk of neurologic impairment and paralysis resulting from an expanding hematoma (especially at sites of traumatic or repeated epidural or spinal puncture). Also, use caution in patients in whom severe liver and kidney dysfunction can produce delayed drug elimination.

Obese patients may be difficult to dose appropriately.

  • Enoxaparin (Lovenox)
    • General surgery (moderate risk) - 2,000 U (20 mg) SC 1-2 h preoperatively, then SC qd postoperatively
    • General surgery (high risk) - 4,000 U (40 mg) SC 1-2 h preoperatively, then SC qd postoperatively or 3,000 U (30 mg) SC q12h starting 8-12 h postoperatively
    • Orthopedic surgery - 3,000 U (30 mg) SC q12h starting 12-24 h postoperatively, or 4,000 U/d (40 mg/d) SC starting 10-12 h preoperatively
    • Acute spinal injury - 3,000 U (30 mg) SC q12h if hemodynamically stable
    • Major trauma - 3,000 U (30 mg) SC q12h starting 12-36 h postinjury
    • Epidural anesthesia - Last dose 12 h prior to pulling catheter; restart more than 2 h afterwards
  • Dalteparin (Fragmin)
    • General surgery (moderate risk) - 2,500 U SC 1-2 h preoperatively, then SC qd postoperatively
    • General surgery (high risk) - 5,000 U SC 8-12 h preoperatively, then SC qd postoperatively
    • Orthopedic surgery - 5,000 U SC 8-12 h preoperatively, then SC qd starting 12-24 h postoperatively
  • Danaparoid (Orgaran)
    • General surgery (high risk)/orthopedic surgery - 750 U SC 1-4 h preoperatively, SC q12h postoperatively
  • Nadroparin (Fraxiparine)
    • General surgery (moderate risk) - 2,850 U SC 2-4 h preoperatively, then SC qd postoperatively
    • Orthopedic surgery - 38 U/kg SC 12 h preoperatively, then SC qd for 3 d, then 57 U/kg/d SC
  • Tinzaparin (Innohep)
    • General surgery (moderate risk) - 3,500 U SC 2 h preoperatively, then SC qd postoperatively
    • Orthopedic surgery - 75 U/kg/d SC starting 12-24 h postoperatively or 4500 U SC 12 h preoperatively, then SC qd postoperatively
  • Ardeparin (Normiflo)
    • Knee surgery - 50 IU/kg SC bid postoperatively for 14 d or until ambulatory

Fondaparinux sodium (Arixtra), a synthetic pentasaccharide, when used once day at 2.5 mg SC qd 6 hours postoperatively, significantly improves the risk-to-benefit ratio for the prevention of postoperative venous thromboembolism.

Other antithrombotic agents

Warfarin, either a fixed or adjusted dose, has an effective but cumbersome DVT prophylaxis regimen, and it is reserved for very high-risk patients who are undergoing general surgery (if the international normalized ratio [INR] is kept at 2-3 with target at 2.5). Direct comparison between warfarin (Coumadin) and other antithrombotic agents has yielded mixed results; however, warfarin is certainly more effective than aspirin or external pneumatic compression.

Direct thrombin inhibitors, such as recombinant hirudin, appear to be superior to LMWH in preventing DVT in studies with venography follow-up, although they are not approved for this indication in the United States.

Antiplatelet agents are generally considered ineffective in preventing PE. Current guidelines advise against the use of aspirin alone in DVT prophylaxis.

Although earlier studies suggest comparable efficacy of dextran in PE prevention, with bleeding risks equivalent to those of heparin, dextran is generally considered less effective than heparin in preventing DVT; furthermore, it can lead to anaphylactoid reactions in 0.1-0.25% of patients. There has been little mention of using dextran in the recent guidelines.

Nonpharmacologic measures

Nonpharmacologic prophylaxis is recommended for low-risk patients throughout the perioperative period until they are ambulatory. These measures are especially useful when heparin therapy is contraindicated. Graduated compression stockings (GCS) and early ambulation have few, if any, complications and are effective for patients who undergo low-risk procedures.

Intermittent pneumatic compression (IPC) is a commonly applied method used to reduce stasis and improve venous return from the lower extremities. IPC has demonstrable efficacy even in patients with moderately high risk; however, if a patient has been at bed rest or immobilized for more than 72 hours, exercise caution in the use of these devices because of the risk of disrupting newly formed clots. These devices are not suitable for patients with injuries or surgical sites in the lower extremities. Newer device designs, such as foot pumps (arteriovenous impulse system), have the same recommendations as those for the IPCs.

Early ambulation remains the most important nonpharmacologic approach to prevention of perioperative DVT and PE. Inferior vena cava filters are no longer recommended in primary prevention for perioperative DVT and PE.

Secondary prevention

Secondary prevention involves the early detection and treatment of subclinical DVT by screening high-risk postoperative patients, particularly those in whom primary prophylaxis is either contraindicated or ineffective. However, the use of routine ultrasonography screening at discharge or during outpatient follow-up is not recommended in asymptomatic patients.



The recommended therapies for prevention of venous thromboembolism based on patient characteristics are as follows, adapted from Seventh ACCP Consensus Conference on Antithrombotic Therapy (for LMWH, low-dose <3,400 anti-Xa units; high-dose >/= 3,400 anti-Xa units):

  • Low-risk patients undergoing general surgery, benign gynecologic surgery, transurethral surgery, or laparoscopic surgery: Recommendation includes early and persistent ambulation without any specific prophylaxis.
  • Moderate-risk patients undergoing general surgery: Recommendations include LDUH (5,000 U bid), LMWH (low-dose), and GCS/IPC.
  • Higher-risk patients undergoing general surgery; patients undergoing major open urologic procedures: Recommendations include LDUH (5,000 U bid), LMWH (high-dose), or IPC.
  • Higher-risk patients undergoing general surgery who are prone to wound complications (eg, hematomas) and infection: Recommendation includes GCS/IPC initially.
  • Very high-risk patients undergoing general surgery who have multiple risk factors, including extensive gynecologic surgery for malignancy or high-risk urologic surgery: Recommendations include LMWH (high-dose), fondaparinux, warfarin (goal INR, 2.5; range, 2-3), or LDUH (5,000 U tid)/LMWH (high-dose) combined with GCS/IPC. Postoperative discharge with LMWH after major cancer surgery.
  • Patients undergoing elective total hip replacement surgery: The optimal duration of prophylaxis is uncertain; 7-10 days is recommended with LMWH or warfarin, and 29-35 days with LMWH may offer additional protection. Recommendation includes LMWH, with the full dose started 12 hours preoperatively or a half dose started 4-6 hours preoperatively, then 12-24 hours postoperatively. Alternatively, warfarin can be started before or immediately after surgery (goal INR, 2.5; range, 2-3) or adjusted-dose heparin can be started preoperatively. Adjuvant use of ES or IPC may be helpful. LDH, aspirin, dextran, and IPC reduce the overall incidence of venous thromboembolism but are less effective.
  • Patients undergoing elective total hip arthroplasty or total knee arthroplasty: The optimal duration of prophylaxis is uncertain; at least 10 days is recommended with LMWH, fondaparinux or warfarin; extending to 27-35 days with LMWH may offer additional protection. Recommendation includes LMWH (high-dose), with the full dose started 12 hours preoperatively or a half dose started 4-6 hours preoperatively, then 12-24 hours postoperatively. Alternatively, half-dose LMWH 2-6 hours postoperatively followed by usual high-dose LMWH the following day can be used. Fondaparinux (2.5 mg daily, 6-8 hours postoperatively) warfarin can be started before or immediately after surgery (goal INR, 2.5; range, 2-3) or adjusted-dose heparin can be started preoperatively. Adjuvant use of GCS or IPC may be helpful. LDUH, aspirin, dextran, and IPC reduce the overall incidence of venous thromboembolism but are less effective.
  • Higher-risk patients undergoing knee arthroscopy, with risk factors or following a prolonged or complicated procedure: LMWH for at least 10 days.
  • Patients undergoing hip fracture surgery: Recommendations include LMWH (high-dose) or adjusted-dose warfarin (goal INR, 2.5; range, 2-3) started preoperatively or immediately after surgery; LDUH is an alternative. Anticoagulation should continue during the time between hospitalization and surgery.
  • High-risk patients undergoing orthopedic surgery: Inferior vena cava filter placement is recommended only if other forms of anticoagulant-based prophylaxis are not feasible because of active bleeding; this is rarely necessary.
  • Patients undergoing intracranial neurosurgery: Recommendation includes IPC with or without GCS. LMWH and LDUH may be acceptable alternatives. Consider IPC or GCC, with LMWH or LDUH, for high-risk patients.
  • Patients with acute spinal cord injury: Recommendation includes LMWH once primary hemostasis is evident. Although GCS and IPC appear ineffective when used alone, GCS and IPC may be of benefit when used with LMWH or if anticoagulants are contraindicated. During rehabilitation, consider continuing LMWH or converting to full-dose oral anticoagulation therapy.
  • Patients with elective spine surgery with advanced age, known malignancy, neurologic deficit, prior DVT, or anterior surgical approach: LDUH, LMWH, or IPC.
  • Trauma patients with an identifiable risk factor for thromboembolism: Recommendations include LMWH as soon as it is considered safe. Consider initial prophylaxis with IPC or GCS if the administration of LMWH is delayed or contraindicated. In high-risk patients (eg, spinal cord injury, lower extremity or pelvic fracture, major head injury, indwelling femoral venous lines) or with suboptimal prophylaxis, consider screening with duplex ultrasonography, and postdischarge LMWH or warfarin, especially in patients with major impaired mobility.
  • Patients with MI: Recommendations include LDUH or full-dose therapeutic intravenous heparin or LMWH. IPC and possibly GCS may be useful when heparin is contraindicated.
  • Patients with ischemic stroke and lower extremity paralysis: Recommendations include LDUH or LMWH. IPC with GCS is probably effective.
  • General medical patients with clinical risk factors for venous thromboembolism, particularly those with heart failure, cancer, or severe lung disease or on bed rest: Recommendations include LDUH or LMWH.
  • Patients with long-term indwelling central vein catheters: Recommendations include warfarin (1 mg/d) or LMWH (low-dose) to prevent axillary-subclavian venous thrombosis.
  • Patients having spinal puncture or epidural catheters placed for regional anesthesia or analgesia: Recommendation includes LMWH, with last dose 12 hours prior to pulling catheter. Do not administer a dose until at least 2 hours after the catheter is pulled.

Types of surgery

A pooled analysis of trials suggests that the rate of DVT following total hip replacement declines from 51% to 11% with the use of LDUH, to 15% with LMWH, and to 22% with IPC or GCS. With LMWH as the prophylactic regimen, the rate of DVT is reduced similarly, from 61% to 31% after total knee replacement and from 48% to 24% after hip fracture surgery.

A smaller number of studies have examined the efficacy of DVT prophylactic regimens for other forms of surgery. Overall, heparin and IPC or GCS are recommended, especially during open prostatectomy (untreated, DVT rate of 31-51%), neurosurgery (untreated, DVT rate of 19-34%), and gynecologic malignancy surgery (untreated, DVT rate of 12-35%).

Comorbidity

The risk of DVT in patients who are untreated after acute MI (25%) is comparable to that following general surgery, and prophylaxis is recommended either in the form of LDUH or full-dose anticoagulation (or IPC or GCS if heparin is contraindicated). In patients with ischemic stroke, pooled data show a reduction in the rate of DVT from 63% to 16%, and to 47% when using unfractionated heparin.

The treatment of patients who present with an established DVT or PE prior to surgery is somewhat different. The risk of thromboembolic complications may increase if the antithrombotic regimen is halted perioperatively. If surgery is elective, patients should undergo a complete course of treatment for DVT or PE before undergoing surgery. Conversely, if surgery is urgent, minimize the duration of antithrombotic cessation and consider placement of a vena cava filter to prevent potential embolization. Switching to a shorter-acting antithrombotic regimen (eg, LDUH) is a frequently used strategy in patients with indications for lifelong anticoagulation (eg, in patients with prosthetic valves).

Hypercoagulability states

The presence of hypercoagulable states (eg, factor V Leiden mutation, protein S or C deficiency, antiphospholipid syndrome) is an indication for the institution of an aggressive perioperative DVT prophylactic regimen. Conduct a diagnostic evaluation preoperatively in patients with a personal or family history of recurrent thromboembolic events. Although the frequency of heparin-induced thrombocytopenia seems to be lower with LMWH than with unfractionated heparin, avoid both regimens in patients with documented heparin sensitivity of this type.



In summary, consider prophylaxis for DVT in all patients undergoing surgery. Preoperative risk stratification determines the level of aggressiveness of DVT prophylaxis. Preoperative anticoagulation is safe and effective when used carefully. When indicated, resume anticoagulant regimens promptly and continue them throughout the postoperative period.

For excellent patient education resources, visit eMedicine's Circulatory Problems Center and Lung and Airway Center. Also, see eMedicine's patient education articles Blood Clot in the Legs and Pulmonary Embolism.



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Perioperative DVT Prophylaxis excerpt

Article Last Updated: Jun 30, 2006