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Perioperative DVT 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 underwent surgical intervention. The true incidence of pulmonary embolism (PE) is unknown, but incidence of fatal PE is estimated to be as high as 5% in patients with DVT. Despite overwhelming evidence for the effectiveness of regimens for DVT prophylaxis, the concern over bleeding risks often dissuades physicians to comply with guidelines.

Pathophysiology

The Virchow triad (stasis, hypercoagulability, intimal injury) often is 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

Common risks factors include the following:

·  Age (older than 40 y)

·  Prolonged immobility (>4 h) or paralysis

·  Prior DVT or PE

·  Obesity

.Hypercoagulable states (factor V Leiden mutation, protein S deficiency, protein C deficiency, antithrombin III deficiency, antiphospholipid antibodies or lupus anticoagulant, plasma hyperhomocystinemia))

·  Major surgery or fractures (especially abdominal, pelvic, lower extremities)

·  Malignancy

·  Varicose veins

·  Heart failure

·  Myocardial infarction (MI)

Management

Goals of therapy

Perioperative prophylactic therapy in patients with risk factors of DVT or PE requires prevention of both occurrence and consequences. Two main strategies exist: nonpharmacologic and pharmacologic. Based on published data, the 1998 American College of Clinical Pharmacy (ACCP) guidelines 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 .

Heparin

This is the mainstay of the pharmacologic approach to DVT prophylaxis. Three common forms of prophylaxis exist: adjusted-dose subcutaneous heparin (ADH), low-dose unfractionated heparin (LDH), and low molecular weight heparin (LMWH). Dosages and indications are summarized in Table 2.

Table 1. Anticoagulation in DVT or PE Prophylaxis*

Evidence for the efficacy of LMWH in perioperative DVT prophylaxis is accumulating. Overall, heparin and LMWH are equivalent in preventing DVT, although LMWH has a greater bioavailability, longer duration of anticoagulant effect in fixed doses, and little requirement for laboratory monitoring (thus, 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.

Protracted 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 risk exists of neurologic impairment and paralysis as a result of 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. A synthetic pentasaccharide, Org31540/SR90107A, recently has been shown to significantly improve the risk-benefit ratio for the prevention of venous thromboembolism as compared with LMWH.

Other antithrombotic agents

Warfarin, either a fixed or adjusted dose, is 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 between 2.0-3.0). Antiplatelet agents generally are considered ineffective in preventing DVT. Although earlier studies suggest comparable efficacy of dextran in PE prevention, with equivalent bleeding risks to heparin, dextran generally is considered less effective than heparin in preventing DVT; furthermore, it can lead to anaphylactoid reactions in 0.1-0.25% of patients.

Nonpharmacologic measures

Nonpharmacologic prophylaxis is recommended for low-risk patients throughout the perioperative period until they are ambulatory. These measures are especially useful when the use of heparin is contraindicated.

Calf-length elastic stockings (ES) 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 bedrest or immobilized for more than 72 hours, exercise caution in the use of these devices, because a risk of disrupting newly formed clots exists. These devices are not suitable for patients with injuries or surgical sites in the lower extremities. Newer device designs, such as foot pumps (arteriovenous [A-V] impulse system), follow the same recommendations as those for the IPCs.

Table 2. Prevention of Venous Thromboembolism 

 

*Adapted from 2000 ACCP Consensus Conference
†Optimal duration of prophylaxis is uncertain; 7-10 days is recommended with LMWH or warfarin; 29-35 days with LMWH may offer additional protection
‡LDH, aspirin, dextran, and IPC reduce the overall incidence of venous thromboembolism but are less effective

Types of surgery

The risk of DVT following elective neurosurgery (24%) is comparable to that following general surgery, but DVT risk nearly doubles after elective total hip replacement (45-57%), total knee replacement (40-84%), or hip fracture surgery (36-60%). A pooled analysis of trials suggests that the prevalence of DVT following total hip replacement declines from 51% to 11% with the use of unfractionated heparin, to 15% with LMWH, and to 22% with IPC or ES. With LMWH as the prophylactic regimen, prevalence of DVT is reduced similarly from 61% to 31% after total knee replacement and from 48% to 24% after hip fracture surgery.

If other forms of anticoagulant-based prophylaxis are not feasible in high-risk orthopedic patients (because of active bleeding), consider prophylactic placement of an inferior vena cava filter placement. Of note, routine screening with duplex ultrasonography is not recommended in asymptomatic patients, even following high-risk surgeries.

A smaller number of studies have examined the efficacy of DVT

prophylactic regimens for other forms of surgery. Overall, heparin and IPC

or ES are recommended, especially during open prostatectomy (untreated

DVT incidence 31-51%), neurosurgery (untreated DVT incidence 19-34%),

                  and gynecologic malignancy surgery (untreated DVT      incidence 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 LDH or full-dose anticoagulation (or IPC or ES if heparin is contraindicated). In patients with ischemic stroke, pooled data show a reduction in the prevalence 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, unfractionated heparin) is a frequently employed 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, protein S/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 in DVT prophylaxis. Preoperative anticoagulation is safe and effective when used carefully. When indicated, resume anticoagulant regimens promptly and continue throughout the postoperative period

BIBLOGRAGHY

• Agnelli G, Piovella F, Buoncristiani P, et al: Enoxaparin plus compression stockings compared with compression stockings alone in the prevention of venous thromboembolism after elective neurosurgery. N Engl J Med 1998 Jul 9; 339(2): 80-5

• Agnelli G, Sonaglia F: Prevention of venous thromboembolism. Thromb Res 2000 Jan 1; 97(1): V49-62

• Bergqvist D, Benoni G, Bjorgell O, et al: Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med 1996 Sep 5; 335(10): 696-700

• Bounameaux H: Integrating pharmacologic and mechanical prophylaxis of venous thromboembolism. Thromb Haemost 1999 Aug; 82(2): 931-7

• Decousus H, Leizorovicz A, Parent F, et al: A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prevention du Risque d'Embolie Pulmonaire par Interruption Cave Study Group. N Engl J Med 1998 Feb 12; 338(7): 409-15

• Friedman RJ, Dunsworth GA: Cost analyses of extended prophylaxis with enoxaparin after hip arthroplasty. Clin Orthop 2000 Jan; (370): 171-82].

• Geerts WH, Heit JA, Clagett GP, et al: Prevention of venous thromboembolism. Chest 2001 Jan; 119(1 Suppl): 132S-175S

• Geerts WH, Jay RM, Code KI, et al: A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med 1996 Sep 5; 335(10): 701-7

• Leclerc JR, Gent M, Hirsh J, et al: The incidence of symptomatic venous thromboembolism during and after prophylaxis with enoxaparin: a multi-institutional cohort study of patients who underwent hip or knee arthroplasty. Canadian Collaborative Group. Arch Intern Med 1998 Apr 27; 158(8): 873-8.