When assessing the cause of deep vein thrombosis (DVT) and pulmonary embolism (PE) in the surgical patient, the triad of stasis, intimal injury, and hypercoagulability contributes to thrombosis. The first arm of the triad is stasis resulting from the supine position and the effects of anesthesia. Nicolaides and coworkers [4] reported delayed clearing of venographic contrast media from the soleal sinuses of the calf in supine patients. Concomitant with this pooling is the vasodilatory effect of anesthesia, which results in increased venous capacitance and decreased venous return from the lower extremities [5,6]. Venous thrombi composed of platelets, fibrin, and red blood cells develop behind the venous valve cusps or the intramuscular sinuses of the calf secondary to decreased blood flow and stasis [7].

The second arm of the triad is intimal injury resulting from excessive vasodilation caused by vasoactive amines (histamine, serotonin, bradykinin) and anesthesia. Studies using scanning and transmission electron microscopy have shown focal tears in the venous endothelium of dogs around valves and branch vessels with accumulation of leukocytes, erythrocytes, and platelets after injection of vasoactive amines, and similar findings were documented after sham abdominal surgery in these animals [8–10].

Hypercoagulability is the third risk factor in the surgical patient. Stasis and surgery set up the conditions conducive to clot formation. The impaired venous blood flow results in a decreased clearance of activated clotting factors, which subsequently set up clot formation on areas of intimal injury and low flow areas such as the posterior valve cusp [11]. Reperfusion of these transiently hypoxic regions of the vessel with oxygenated blood induces thrombus, impairing venous valve function and promoting growth of thrombus beyond this localized area [12]. Other factors have been assessed such as fibrinopeptide A, platelet factor 4, b-thromboglobulin, d-dimers, antithrombin (AT), a₂-antiplasmin, factor VIII activity, von Willebrand factor antigen, thrombin/antithrombin ratio, fragments 1 + 2, tissue plasminogen activator inhibitor, and decreased plasmin activity [13–17]. None of these factors has been shown to be sensitive and specific in predicting which patients are at risk for the development of DVT.

The ACCP advocates a unified approach to VTE risk assessment by assigning risk according to the type of surgery, mobility, and individual risk factors (Box 1, Table 1) [1]. The patient can be classified as being at low, moderate, or high risk for the development of VTE. Low-risk patients are those who are mobile and are having minor surgery. Medical patients who are fully ambulatory are also considered to be at low risk. Based on studies using objective, diagnostic screening for asymptomatic DVT in patients not receiving prophylaxis, the approximate DVT risk is less than 10% in patients assigned to the low-risk category. Moderate-risk patients are those undergoing general, open gynecologic, or urological surgery. The approximate incidence of DVT risk without thromboprophylaxis in this group is 10% to 40%. The high-risk group includes patients having hip or knee replacement, fractured hip surgery, major trauma, and acute spinal cord injury. The DVT risk without thromboprophylaxis in this category is between 40% and 80%.

Table 1 Classification of the risk of postoperative venous thrombosis and PE

Data from Geerts WH, Bergqvist, Pineo G, et al. Prevention of venous thromboembolism. Chest 2008;133:381S–453S.

Another approach to risk assessment is the Caprini Risk Assessment Model (Fig. 1) [18]. This method consists of a list of exposing risk factors (genetic and clinical characteristics), each with an assigned relative risk score. The scores are summed to produce a cumulative score, which is used to classify the patient into 1 to 4 risk levels and determines the type and duration of VTE prophylaxis. This risk assessment tool was validated by Bahl and colleagues [19].

Fig. 1 VTE risk factor assessment.

(Courtesy of Joseph A. Caprini, MD, MS, FACS, RVT.)

There are 6 recognized modalities of prophylaxis for VTE and each should be administered in its own specific manner. In this section, each method is reviewed with respect to dose, administration, and length of therapy.

Dalteparin: 5000 units SC every 24 hours (initiated evening of surgery). Fondaparinux: 2.5 mg, SC beginning 6 hours after surgery then once daily. Enoxaparin: orthopedic surgery 30 mg SC every 12 hours (initiated evening of surgery) and all other surgeries 40 mg SC every 24 hours (initiated evening of surgery).

Abbreviations: THA, total hip arthroplasty; TKA, total knee arthroplasty.

Low-molecular-weight heparins (LMWHs) also catalyze the activation of antithrombin (see Table 2). However, this group of heparins has been observed to have a more significant inhibitory effect on factor Xa than factor IIa as well as a lower bleeding risk than standard heparin [23]. These agents are not bound to plasma proteins (histidine-rich glycoprotein, platelet factor 4, vitronectin, fibronectin, and von Willebrand factor), endothelial cells, or macrophages like standard heparin [16,24]. This lower affinity contributes to a longer plasma half-life, more complete plasma recovery at all concentrations, and a clearance that is independent of dose and plasma concentration. They have been shown to be safe and effective for the prevention of postoperative VTE in orthopedic and general surgery [25,26]. Currently, 6 LMWH preparations are approved for use in Europe, whereas in the United States enoxaparin and dalteparin are available for orthopedic and general surgery, respectively. Each of these drugs has a different molecular weight, antiXa to anti-IIa activity, rates of plasma clearance, and recommended dosage regimens [24].

The newest, injectable anticoagulant is fondaparinux. This drug is a synthetic analogue of the pentasaccharide sequence of heparin that specifically binds to antithrombin. It has a longer half-life (17–21 hours) than the other agents and has more specificity for factor Xa inhibition than LMWH. It has been shown to be safe and effective in patients undergoing knee and hip replacement procedures as well as hip fracture and abdominal surgeries.

Both LMWH and fondaparinux are renally excreted and are contraindicated in patients with renal impairment. Protamine partially reverses the anticoagulant effects of LMWH and is ineffective as an antidote to fondaparinux [1]. Enoxaparin is initiated 12 to 24 hours after orthopedic surgery at 30 mg SC every 12 hours. For all other surgeries enoxaparin is administered at 40 mg SC once daily. Dalteparin is administered 2 hours before general abdominal surgery at 2500 units SC and then once daily at 2500 units or 5000 units. Fondaparinux is given at 2.5 mg SC once daily beginning 6 hours after surgery.

Warfarin has been studied and approved for use in patients undergoing orthopedic surgery (see Table 2) [1]. It can be administered by 2 methods. The first approach is to begin this medication on the evening before the day of surgery, whereas the second method involves the initiation of this drug on the day of the procedure. The usual starting dose of warfarin is 5 mg and the dose is adjusted for a goal international normalized ratio (INR) between 2 and 3. A loading dose of coumadin in excess of 5 mg is generally not recommended and lower starting doses may be considered for patients who are elderly, have impaired nutrition, or who have liver disease or congestive heart failure [1]. The duration of prophylaxis is maintained for up to 35 days at an INR goal of 2 to 3 with some studies using an INR of 1.8 to 2.5. The rare complication of warfarin-induced skin necrosis has never been reported in studies using this agent as prophylaxis for DVT and PE.

In some institutions, a debate exists regarding the most appropriate VTE prophylaxis in orthopedic patients that adequately balances the risk of bleeding with efficacy. A meta-analysis by Mismetti and colleagues [27] concluded that LMWH is more effective in reducing the risk of venographically detected and proximal DVT compared with vitamin K antagonists. However, there was no difference in the rate of PE between these 2 classes of medications with a similar to slightly greater risk of bleeding associated with LMWH. The ACCP guidelines have also acknowledged a greater efficacy of LMWH and, by indirect comparisons, fondaparinux in preventing both asymptomatic and symptomatic VTE in orthopedic patients at a cost of a slight increase in surgical site bleeding [1]. The postulated reason for this finding is a quicker onset of action with LMWH and fondaparinux compared with warfarin.

Various forms of mechanical prophylaxis exist and include intermittent pneumatic compression, graduated compression stockings, and venous foot pumps. The main advantage of these products is the lack of a potential for bleeding with their use. Studies have shown them to be effective in reducing the rate of DVT, but not PE or death, in various surgical populations and they may provide additive efficacy when combined with anticoagulants. However, they have generally been found to be less effective than the pharmacologic prophylactic modalities and have not been so vigorously studied as the anticoagulants. A lack of compliance with these devices has been observed and should be taken into account, along with their respective costs, before their use [1].

External pneumatic compression sleeves are mechanical methods of improving venous return from the lower extremities [28]. They reduce stasis in the gastrocnemius-soleus pump. They are placed on the patient on the morning of surgery and are worn throughout the surgical procedure and continuously in the postoperative period until the patient is ambulatory or an anticoagulant is started. The most common complaints pertain to local discomfort caused by increased warmth, sweating, or disturbance of sleep. If a patient has been at bed rest or immobilized for more than 72 hours without any form of prophylaxis, it is our practice to perform lower extremity noninvasive testing to ensure that the patient does not have a DVT before the application of the sleeves.

Mechanical foot compression operates by compressing the sole of the foot, which activates a physiologic pump mechanism and improves venous return in the lower extremity. The venous foot pump was developed to accomplish this function. Like the external pneumatic compression sleeves, this device is worn during and after the surgery until the patient is ambulatory or the device is replaced by a pharmacologic agent. The venous foot pump has not been shown to be as effective as the external pneumatic compression sleeves.

Calf-length gradient elastic stockings are worn during surgery and are maintained until the patient is discharged. There are no known complications from their use. These mechanical methods of prophylaxis are effective for low-risk procedures. As with all other mechanical modes of prophylaxis, these products must be worn continuously to be effective.

There is a lack of consensus on the role of aspirin for the prevention of VTE in the orthopedic population. The American Association of Orthopedic Surgeons (AAOS) endorses the use of aspirin for certain patients who undergo nontraumatic hip or knee arthroplasty whereas the ACCP recommends against the use of aspirin for any patient undergoing a joint replacement procedure [1,2]. The AAOS places an emphasis on reducing the risk of symptomatic PE and cites a lack of a clear correlation between the presence of a lower extremity DVT and the risk of subsequently developing a symptomatic PE. On the other hand, the ACCP endorses the presence of a lower extremity DVT as a marker for an increased risk of PE and, thus, places an emphasis on reducing the risk of developing a lower extremity thrombus. Warfarin, LMWH, and the synthetic pentasaccharide have been shown to more effectively reduce this risk and, thus, are recommended by the ACCP. However, the AAOS recommends the use of aspirin in patients with a standard risk of PE and major bleeding or in those with an increased risk of major bleeding with a standard risk of PE because there is evidence to suggest a decrease in the rate of symptomatic events with the use of aspirin. There are no recommendations for aspirin use in the other surgical groups.