eMedicine Specialties > Perioperative Care > Perioperative Care

Perioperative DVT Prophylaxis

Author: Girish R Mood, MBBS, MD, MRCS, Fellow, Department of Vascular Medicine, Cleveland Clinic Foundation
Coauthor(s): Wai Hong Wilson Tang, MD, Assistant Professor of Medicine, Section of Heart Failure and Cardiac Transplantation Medicine, Cleveland Clinic Foundation
Contributor Information and Disclosures

Updated: Jan 14, 2009

Background

Deep venous thrombosis (DVT) is a common but highly preventable perioperative complication. The risk for deep venous thrombosis (DVT) has been reported to be highest in critical care and spinal cord injury patients (60-80%). Following general surgery procedures, the approximate risk for deep venous thrombosis (DVT) is 15-40%. This risk nearly doubles after hip or knee replacement surgery or hip fracture surgery (40-60%).¹

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 0.2-0.9% of patients undergoing elective general surgery, 0.1-2% of those undergoing elective hip replacement, and up to 2.5-7.5% of those undergoing surgery for a fractured hip.² Despite overwhelming evidence for the effectiveness of regimens for deep venous thrombosis (DVT) prophylaxis, the concern over bleeding risks often dissuades physicians to comply with guidelines.

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.

Related eMedicine topic:
Deep Venous Thrombosis Prophylaxis in Orthopedic Surgery [in the Orthopedic Surgery section]

Pathophysiology

The Virchow triad (ie, stasis, hypercoagulability, intimal injury) is often used to explain the development of deep venous thrombosis (DVT). The first component of the triad is stasis, which is a result of the venous pooling due to 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 vasodilatation 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 deep venous thrombosis (DVT).³

Risk Factors

Risk factors for developing short-term (30-day) postoperative risk for deep venous thrombosis (DVT) have been examined in a prospective cohort of 21,903 consecutive surgical patients and include the following⁴ :

• 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 deep venous thrombosis (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.⁵

The strongest risk factor (odds ratio >10) for venous thromboembolism (VTE) was seen after hip or leg fracture/replacement, major general surgery, major trauma, or spinal cord injury. A moderate risk factor (odds ratio 2-9) was associated with central venous catheters, arthroscopic knee surgery, hormone replacement therapy (HRT), congestive heart failure (CHF), malignancy, pregnancy (postpartum), previous cerebrovascular accident (CVA) or deep venous thrombosis (DVT), and thrombophilia. A lesser risk factor was associated with laparoscopic surgery, varicose veins, increasing age, and obesity.

Management

Goals of therapy

Perioperative (or primary) prophylactic therapy in patients with risk factors for deep venous thrombosis (DVT) or PE requires prevention of both the occurrence and the consequences of deep venous thrombosis (DVT) or PE. The 2 main strategies are nonpharmacologic and pharmacologic interventions. Patients are classified as having low, moderate, high, and very high risks for the development of deep venous thrombosis (DVT) or PE, and the prophylactic regimens are used according to this risk stratification.

Risk levels of Thromboembolism Risk and Recommended Thromboprophylaxis in Hospital Patients¹

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bid = twice daily; INR = international normalized ratio;LDUH = low-dose unfractionated heparin; LMWH = low molecular weight heparin; tid = three times daily.

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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 of 20,000-100,000/µL, brain metastases or recent major trauma, major abdominal surgery within the past 2 days, gastrointestinal or genitourinary bleeding within the past 14 days, infective endocarditis, or malignant hypertension.

Deep venous thrombosis (DVT) prophylaxis for trauma and surgical patients based on the EighthAmericanCollege of Chest Physicians (ACCP) Consensus Conference are follow.¹

Pharmacologic therapy includes LMWH 40 mg subcutaneously (SC) daily, LDUH 5000 units SC 2-3 times daily, or fondaparinux 2.5mg SC daily. Patients with renal insufficiency (creatinine clearance [CrCl] <30mL/min) should not receive fondaparinux. However, LDUH and LMWH can be used with caution and careful monitoring of the levels or their anticoagulant effects to avoid bioaccumulation.

Patients undergoing surgery involving low-risk procedures and who have no associated risk factors for deep venous thrombosis (DVT) do not require specific thromboprophylaxis. However these patients should be encouraged to ambulate early and frequently. Thromboprophylaxis for moderate- and high-risk surgical procedures are outlined below¹ :

General surgery

• Benign disease: LMWH, LDUH (2-3 times daily), or fondaparinux (daily) (grade 1A)
• Malignant disease: LMWH, LDUH (3 times daily), or fondaparinux (daily) (grade 1A)
• Multiple risk factors for venous thromboembolism: LMWH, LDUH, or fondaparinux + mechanical methods (grade 1C).
• High risk for bleeding: Mechanical methods until the bleeding risk improves (grade 1A), following which pharmacologic methods should be considered (grade 1C)

Patients who have undergone major surgical procedures should receive prophylaxis until discharge from the hospital. If these patients have associated significant risk factors for deep venous thrombosis (DVT) or have undergone cancer surgery, prophylaxis with LMWH should be continued up to 28 days after the surgery (grade 2A).

Vascular surgery

• Major procedures with risk factors for deep venous thrombosis (DVT): LMWH, LDUH, or fondaparinux (grade 1C)

Gynecologic surgery

• Laparoscopic procedures with risk factors for deep venous thrombosis (DVT): LMWH, LDUH, +/– IPC or GCS (grade 1C)
• Major procedures: LMWH, LDUH, or fondaparinux (grade 1A)

Patients undergoing major procedures including cancer surgeries should be started on deep venous thrombosis (DVT) prophylaxis the day before the surgery and continue therapy up to ambulation. Selected patients who have a high risk and who are on prolonged bed rest should receive prophylaxis until discharge. Patients with previous history of venous thromboembolism are suggested to receive LMWH for up to 28 days from surgery (grade 2C).

Urologic surgery

• Major, open procedures: LMWH, LDUH, or fondaparinux (grade 1A)
• High risk for bleeding: Mechanical methods until the bleeding risk improves (grade 1A), following which pharmacologic methods should be considered (grade 1C)

Laparoscopic surgery

• With a previous deep venous thrombosis (DVT) or PE: LMWH, LDUH, +/– IPC or GCS (grade 1C)

Bariatric surgery

• LMWH, LDUH, or fondaparinux +/– IPC (grade 1C)

Thoracic surgery

• Major procedures: LMWH, LDUH, or fondaparinux (grade 1C)
• High risk for bleeding: Properly fitted GCS and or IPC (grade 1C)

Coronary artery bypass surgery

• LMWH, LDUH +/– IPC or GCS (grade 1C)
• High risk for bleeding: Properly fitted GCS and or IPC (grade 1C)

Elective hip/knee replacement surgery

• LMWH started 12 hours before or 12-24 hours after the procedure; or start with a half dose 4-6 hours after surgery, with a full dose the next day; OR
• Fondaparinux 2.5 mg SC started 6-24 hours after surgery;  OR
• Adjusted dose vitamin K antagonist, starting 1 day before the surgery with a target INR of 2-3.0 (grade 1A).
• Pharmacologic therapy continued for a minimum of 10 days (up to 35 days) after surgery
• High risk bleeding: Optimal use of VFP or IPC (grade 1A).

Hip fracture surgery

• Same as above;  OR
• LDUH 5000 units SC 2-3 times daily, started at the time of admission

Elective spine surgery

• Patients with a high risk for deep venous thrombosis (DVT) or PE should receive postoperative LDUH, LMWH +/– GCS, IPC

Isolated, distal-to-the-knee surgery

• No specific therapy

Neurosurgery

• Major procedures: Postoperative LMWH or LDUH +/– GCS or IPC (grade 2B)

Trauma/burns/spinal cord injury

• Bleeding complications: Mechanical methods with GCS or IPC; duplex surveillance only in patients at high risk for deep venous thrombosis (DVT)
• LMWH, when safe to use

Heparin

Heparin is a highly sulfated mucopolysaccharide with molecular weight between 3,000 to 15,000. The pentasaccharide sequence of this heparin molecule is responsible for its anticoagulant effect.⁶ Heparin is cleared by rapid phase by binding to endothelial receptors and macrophages⁷ or by slower renal clearance. The therapeutic effect of intravenous heparin is monitored by activated partial thromboplastin time (aPTT) levels between 1.5 to 2.5 times the control aPTT.

LDUH was favored in the treatment of deep venous thrombosis (DVT), as this agent was effective in the prevention of venous thromboembolism, including deep venous thrombosis (DVT) and fatal PE. In addition, this therapy was easy to administer, cost effective, and did not require frequent blood monitoring.⁸  There was also reduced incidence of major bleeding with this therapy.⁹

LMWH

LMWH is one-third the molecular weight of unfractionated heparin, and it is widely used in the perioperative setting for deep venous thrombosis (DVT) prophylaxis. Overall, heparin and LMWH are equivalent in preventing deep venous thrombosis (DVT), although LMWH has a greater bioavailability, a longer duration of anticoagulant effect in fixed doses, and little requirement for laboratory monitoring (and, thus, is more cost effective).

Postoperative use of LMWH (up to 2-3 wk after hospital discharge) results in a lower frequency of deep venous thrombosis (DVT).¹⁰ LMWH should be used with caution in patients with spinal punctures or epidural catheters because of the risk of neurologic impairment and paralysis that result 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.

Use of heparin products can result in the development of antibodies against platelets, causing heparin-induced thrombocytopenia (HIT). Unfractionated heparin is more associated with HIT compared with LMWH. To eliminate this serious complication, direct thrombin inhibitors or synthetic pentasaccharides are used.  

Fondaparinux sodium (Arixtra)

Fondaparinux isa synthetic pentasaccharide that, when used once a day at 2.5 mg SC qd 6 hours postoperatively, significantly improves the risk-to-benefit ratio for the prevention of postoperative venous thromboembolism. It has a longer half life compared WITH LMWH (17h vs 4h). Fondaparinux reaches steady state after 3-4 doses and is excreted through the urine unchanged. Hence, it is not indicated in patients with a CrCl <30mL/min. Because it produces a predictive therapeutic response, single once-a-day dosing of fondaparinux is preferred with no monitoring.¹¹

Fondaparinux has been proven to be superior to LMWH, especially in the treatment of patients following knee replacement surgery.¹²


Other antithrombotic agents

Warfarin, as either a fixed or adjusted dose, has an effective but cumbersome deep venous thrombosis (DVT) prophylaxis regimen, and it is reserved for very high-risk patients who are undergoing general surgery (if the INR is kept at 2-3, with a target of 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.¹³

Direct thrombin inhibitors, such as hirudin, are extracted from the salivary glands of medicinal leeches. There are 2 recombinant forms of hirudin available, lepirudin and desirudin. Lepirudin is approved in the US for the treatment of thrombosis associated with HIT. Desirudin appears to be superior to LMWH in preventing deep venous thrombosis (DVT) in studies with venography follow-up.¹⁴ Currently, desirudin is approved by the US Food and Drug Administration (FDA) for venous thrombosis after hip surgery.

Bivalirudin, an analogue of hirudin, and Argatroban, a competitive inhibitor of thrombin, are other direct thrombin inhibitors that are used in the treatment of thrombosis associated with HIT. However, bivalirudin is currently approved by the FDA only for the use in patients with HIT who are undergoing percutaneous coronary intervention.

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

Although earlier studies suggested 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 deep venous thrombosis (DVT); furthermore, it's use can lead to anaphylactoid reactions in 0.1-0.25% of patients. Use of dextran has been contraindicated as a deep venous thrombosis (DVT) prophylaxis therapy in the recent guidelines.¹

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. GCS and early ambulation have few, if any, complications and are effective for patients who undergo low-risk procedures.

IPC is a commonly applied method that is used to reduce stasis and improve venous return from the lower extremities. IPC has demonstrable efficacy even in patients at moderately high risk for deep venous thrombosis (DVT). 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.¹⁵

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

Secondary prevention

Secondary prevention involves the early detection and treatment of subclinical deep venous thrombosis (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.

• Patients with myocardial infarction (MI): Recommendations include LDUH or unfractionated 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 who are on bed rest: Recommendations include LDUH or LMWH.
• Patients having spinal puncture or epidural catheters placed for regional anesthesia or analgesia: Recommendation includes LMWH, with  the last dose 12 hours before pulling the catheter. Do not administer a dose until at least 2 hours after the catheter is pulled.

Special Considerations

Comorbidity

The risk of deep venous thrombosis (DVT) 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 general, medical patients have much higher risk for symptomatic deep venous thrombosis (DVT)(50-70%) and PE (70-80%).¹⁶ Meta-analysis of patients with ischemic stroke showed a 70% reduction in the rate of deep venous thrombosis (DVT) with the use of LMWH or unfractionated heparin.¹⁷

Patients with mechanical valves on lifelong anticoagulation should discontinue their warfarin 3 days before surgery, although aortic valves have a lower risk of embolization than mitral valves when anticoagulation is discontinued. In high-risk patients, unfractionated heparin may be used during the period without adequate warfarin therapy; however, few data in the literature demonstrate a safe duration of subtherapeutic anticoagulation.

The treatment of patients who present with an established deep venous thrombosis (DVT) or PE before surgery is somewhat different. The risk of thromboembolic complications may increase if the antithrombotic regimen is halted perioperatively. If the surgery is elective, patients should undergo a complete course of treatment for deep venous thrombosis (DVT) or PE before undergoing surgery. The duration of treatment can vary from 3 to 6 months, according to the clinical events. Conversely, if the surgery is urgent, minimize the duration of antithrombotic cessation and consider placement of a vena cava filter to prevent potential embolization.

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 deep venous thrombosis (DVT) prophylactic regimen. Complete evaluation of a patient's personal or family history of recurrent thromboembolic events should be done preoperatively. Although the frequency of HIT seems to be lower with LMWH than with unfractionated heparin, avoid both regimens in patients with documented heparin sensitivity of this type.

Duration of therapy

Anticoagulation prophylaxis is thought to be necessary until the hospital discharge (~10 days). However there are data showing an increased incidence of asymptomatic deep venous thrombosis (DVT) (15-20%) following hip surgery in spite of 1-2 weeks of thromboprophylaxis after surgery.¹⁸ There is strong evidence for reports of persistent coagulation cascade activation for up to 4 weeks and the risk for thrombosis for up to 3 months after total hip replacement surgery.¹⁹ Hence, it is advised to considered a longer duration of prophylaxis (28-35 days) for patients with moderate to high risk for venous thrombosis.²⁰

Following orthopedic surgery, routine screening for deep venous thrombosis (DVT) in asymptomatic patients before hospital discharge is not recommended (grade 1A).

Conclusion

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

Keywords

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

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