Venous Thromboembolism in Total Hip Arthroplasty

Genetic hypercoaguable states (Factor V Leiden deficiency, Protein C or S deficiency, lupus anticoagulant, thrombophilias)

History of prior DVT and/or PE

History of prior congestive heart failure, myocardial infarction, and/or stroke

Advanced age

Obesity

Smoking

Major or minor trauma

Pregnancy

Oral contraception

Malignancy

Prolonged immobilization

Recent surgery or hospitalization within 3 months

Pathophysiology

In order to understand the diagnosis and treatment of VTE, it is important to first understand how and why clots are formed. This begins with an appreciation of Virchow’s triad: blood flow (stasis), blood vessel wall (endothelial damage), and blood clotting components (hypercoaguability). Thrombus formation occurs when there are abnormalities involving one or more of these elements, resulting from either hereditary or acquired factors. This leads to an imbalance in the normal homeostasis that exists between clot formation and degradation [18, 19].

Thrombi formation begins at a location with vessel damage and stagnant blood flow. Reduced blood flow in combination with the avascular nature of venous valves predisposes the epithelium at these sites to hypoxic damage [20]. This insult to the tissue then attracts tissue factor and activated factor VII, initiating the coagulation cascade, seen in Fig. 13.1. Red blood cells, and to a lesser extent platelets, become entrapped within the fibrin clot that forms as the product of the coagulation cascade [21].

Fig. 13.1

Depiction of the coagulation cascade (VKA vitamin K antagonist, LMWH low molecular weight heparin, P platelets, TF tissue factor)

Once a thrombus has formed, the process of degradation begins. Fibrinolysis can lead to complete or partial resolution of the clot by converting plasminogen to plasmin, an enzyme that breaks down fibrin. If partial resolution occurs, one of three outcomes can ensue: clot organization, extension, or embolization. During organization, inflammatory cells cause remodeling and incorporation of the clot into the vessel wall. This allows for continued blood flow, but also, leads to scarring, damage to the venous valves, and venous reflux disease, which is associated with edema and varicose veins. This can result in chronic venous insufficiency or post-thrombotic syndrome [21]. Clot extension occurs as the thrombus propagates proximally, in the direction of blood flow. Traditionally it was thought that embolization occurred when a clot in the lower extremity migrated to the pulmonary arteries causing a pulmonary embolism [22]. However, this has become a point of contention, due to numerous studies demonstrating a low percentage of DVTs in patient with pulmonary embolism, leading to the argument that pulmonary embolism may in fact originate de novo in the lungs [23–25]. There is agreement that an embolus can obstruct the pulmonary bed and both respiratory and hemodynamic consequences can occur. The severity of the pulmonary embolism depends on a number of factors including the size and number of emboli, the underlying condition of the lungs, and the body’s ability to respond to the insult. This can result in hypoxemia, pulmonary hypertension, right-sided heart failure, and even death [13].

Prophylaxis

Because VTE can have fatal consequences, and orthopedic patients are at a considerable risk, it is well accepted that patients undergoing surgery about the hip should receive some form of prophylaxis. A number of methods are used, including both mechanical and pharmacologic agents. The selection of which prophylactic agent to use is a balance between efficacy and safety.

Mechanical Prophylaxis

Intermittent pneumatic compression devices, which can be applied to the feet or calves, act by increasing venous return and decreasing stasis. There has been some evidence to support that they additionally stimulate fibrinolysis, although the clinical significance is still uncertain [26]. The benefit of compression devices is they do not carry the risk of bleeding that the pharmacologic agents do, however, the efficacy is dependent on patient compliance and appropriate usage. Therefore, it is essential that the patient and the nursing staff are educated regarding the importance of, and appropriate use of such devices [27]. Additionally, a recent study evaluated the efficacy of a portable compression device for home use following hospital discharge for a minimum of 10 days. This registry study demonstrated a non-inferior risk of symptomatic VTE when mechanical compression was used alone or in conjunction with aspirin when compared to multiple pharmacologic agents, including warfarin and enoxaparin [28].

Graduated compression devices are a second method of providing mechanical means to reduce stasis, and do so by creating a pressure gradient between the distal and proximal veins [29]. Although used commonly in addition to pneumatic compression and/or chemoprophylaxis, there is currently no data to support their use as an independent method of prophylaxis.

Another method of mechanical prophylaxis is the inferior vena cava (IVC) filter. IVC filters are metal implants that are inserted percutaneously, into the IVC, and act as a barrier to blood clots, while their porosity allows for continued blood flow. However, placement of the filters does carry risks, and this must be weighed against the benefits when determining their role in prophylaxis. In general, filter use is considered only in high-risk patients in which chemoprophylaxis is contraindicated, despite prior history of DVT and/or pulmonary embolism [30].

Chemoprophylaxis

Many pharmacological agents are now available for DVT prophylaxis (Table 13.2).

Table 13.2

Anticoagulation agents

	Advantages	Disadvantage
Aspirin	Oral, no monitoring needed	More data needed
Warfarin	Oral, ability to titrate, reversible	Frequent monitoring required, food/drug interactions
Low molecular weight heparin	No monitoring required	Subcutaneous, bleeding risks
Unfractionated heparin	No monitoring required	Subcutaneous, frequent dosing, risk of HIT
Fondaparinux	No monitoring required	Subcutaneous, bleeding risk
Rivroxaban	Oral, no monitoring needed	Ideal timing of administration unknown, bleeding risk
Apixaban	Oral, no monitoring needed	No FDA approved, bleeding risk
Dabigatran	Oral, no monitoring needed	Few studies

Aspirin, an antiplatelet agent, has been investigated in the prevention of VTE, due to its ease of administration and lack of required monitoring. The Pulmonary Embolism Prevention trial, a randomized control trial, evaluated the use of asprin compared to placebo following both hip fracture surgery and hip arthroplasty [31]. Although aspirin was shown to decrease the rates of DVT and PE in patients with hip fractures when compared to placebo, this did not hold true for patients who underwent elective total hip arthroplasty. In regard to bleeding, however, there is no increased risk of bleeding with aspirin as compared to placebo [31–33]. A more recent British registry study comparing aspirin to low molecular weight heparin (LMWH) demonstrated no significant difference on venous thrombotic events or major bleeding. When this data was further analyzed using matched control groups, they noted a significant increase in 90-day mortality in patients receiving aspirin compared to those receiving LMWH [34]. In order to determine the relative efficacy and safety of aspirin, there needs to be multicenter randomized control trials comparing aspirin to other agents, such as LMWH or the newer oral anticoagulants.

Warfarin, a vitamin K antagonist, functions by preventing the activation of factors II, VII, IX, X, as well as protein C and S. While multiple randomized control trials have demonstrated inferiority in efficacy when compared LMWH in preventing overall clot formation [35, 36], a multicenter clinical trial comparing warfarin to enoxaparin showed no difference in symptomatic events after hospital discharge [37]. Additionally, trials have demonstrated lower bleeding rates with use of warfarin when compared to LMWH [32]. Many surgeons prefer the use of warfarin due to the ability to titrate dosing to a desired INR, its reversibility with administration of vitamin K, and its oral route of administration. However, the numerous food interactions and frequent lab monitoring can be difficult with respect to patient compliance.

LMWH, which includes agents such as fragmin and enoxaparin, acts by inhibiting factor Xa in the coagulation cascade. LMWHs are effective anticoagulants and no monitoring is required, but there has been concern among orthopedic surgeons about bleeding and wound drainage associated with LMWH prophylaxis. While numerous trials have demonstrated significant reduction in rates of DVT formation compared to warfarin, there has been no proven difference in rates of symptomatic VTE events. In general, LMWH is initiated either 12 h prior to surgery or 12–24 h postoperatively, with either daily or twice a day dosing. While LMWH does not require any monitoring, there is some evidence of increased bleeding rates compared to warfarin [32, 33, 35, 37]. With that in mind, LMWH should not be used in patients with indwelling epidural catheters.

Fondaparinux, an indirect factor Xa inhibitor administered subcutaneously, has been shown to decrease the incidence of asymptomatic DVTs compared to enoxaparin (an LMWH) in patients with hip fractures. However, the increased incidence of bleeding risks in total knee arthroplasty patients has limited its use in the United States [38]. It is also not recommended in patients with renal insufficiency.

Two additional direct factor Xa inhibitors have been recently studied, rivaroxaban and apixaban. Both are oral agents that require no monitoring, and have been shown to be effective in VTE prophylaxis with decreased rates of thromboembolism and death when compared directly to enoxaparin in randomized trials. Apixaban was also noted to be associated with decreased bleeding complications [32, 33, 39], but has not yet been approved for use in VTE prophylaxis by the FDA. There are current concerns regarding bleeding risks with the use of rivaroxaban, as it is a potent anticoagulant. A recent systematic review of the literature comparing rivaroxaban and LMWH demonstrated a reduced risk of symptomatic events, but an increased risk of major bleeding [40]. In the randomized trials assessing rivaroxaban, the drug was administered approximately six hours after surgery. While it may be safe to administer the drug the morning after surgery, the efficacy of this regimen needs to be assessed.

Dabigatran is an oral direct thrombin inhibitor, which has previously used for atrial fibrillation and stroke prophylaxis, and was recently approved by the FDA for VTE prophylaxis. In the RE-COVER and RE-COVER II randomized trials, dabigatran was found to be non-inferior to warfarin in prevention of symptomatic events. Although it was not associated with decreased rates of overall bleeding, it was found to have higher rates of gastrointestinal bleeding [41, 42]. Additional studies comparing dabigatran to enoxaparin have shown non-inferiority and equivocal bleeding risks as LMWH [32].

Guidelines for VTE Prophylaxis

Guidelines have been developed by both the American Academy of Orthopedic Surgeons (AAOS) and the American College of Chest Physicians (ACCP) in order to enable clinicians to provide effective and safe prophylaxis regimens for their patients.

In 2011, AAOS published a guideline that contains ten recommendations related to VTE prophylaxis [43]. These recommendations were primarily aimed towards elective total hip and total knee arthroplasty, and were based on a systematic review of the literature. The goal is to reduce the rates of symptomatic events, while balancing bleeding risks. Each recommendation was graded individually by the level of evidence supporting it. The guideline does not make a specific recommendation regarding the optimal prophylaxis regimen or duration of prophylaxis because of the limited number of randomized trials assessing the impact of prophylactic agents on symptomatic events. The guidelines did, however, make a strong recommendation against routine screening for VTE at the time of hospital discharge. A summary of the AAOS guidelines can be found in Table 13.3.

Table 13.3

AAOS guidelines for VTE prophylaxis

1. Recommendation against screening for DVTs in postoperative patients who undergo elective hip or knee arthroplasty (Grade: Strong)

2. Assessment of history of prior VTE (Grade: Limited)

3. Assessment of bleeding disorders of liver disease which increase the risk of bleeding and associated complications in patients who undergo elective hip or knee arthroplasty (Grade: Consensus)

4. Recommendation to discontinue the use of antiplatelet agents prior to elective hip or knee arthroplasty (Grade: Moderate)

5. Recommendation for the use of mechanical compressive devices and/or systemic chemoprophylaxis for the prevention of VTE in patients who undergo elective hip or knee arthroplasty (Grade: Moderate)

6. Recommendation for the use of mechanical compressive devices and systemic chemoprophylaxis for the prevention of VTE in patients who undergo elective hip or knee arthroplasty who have history of DVT/PE (Grade: Consensus)

7. Recommendation for the use of mechanical compressive devices for the prevention of VTE in patients who undergo elective hip or knee arthroplasty who have acute liver disease and/or a bleeding disorder (Grade: Consensus)

8. Recommendation for early mobilization in patients who undergo elective hip or knee arthroplasty (Grade: Consensus)

9. Recommendation for neuraxial anesthesia in patients who undergo elective hip or knee arthroplasty to prevent blood loss (Grade: Moderate)

10. Unable to recommend for or against the use of inferior vena cava filters to prevent pulmonary embolism in patients who undergo elective hip or knee arthroplasty and have a contraindication to systemic chemoprophylaxis or residual VTE disease (Grade: Inconclusive)

Summary of the 2011 American Academy of Orthopedic Surgeon’s clinical practice guidelines for the prophylaxis of venous thromboembolism in patients undergoing elective hip or knee arthroplasty.

The ACCP published their most recent guidelines for VTE prophylaxis for total joint arthroplasty patients in 2012 [44]. In contrast to prior ACCP guidelines, the 2012 recommendations now focus on balancing efficacy and perioperative bleeding. These guidelines highlight the recommendations for a combination of systemic and mechanical modalities in elective arthroplasty (Table 13.4).

Table 13.4

ACCP guidelines for VTE prophylaxis in orthopedic patients

Patients undergoing elective THA or TKA

Recommendation for the use of chemoprophylaxis for minimum of 10–14 days versus with one of the following: LMWH, fondaparinux, apixiban, dabigatran, rivaroxaban, low-dose unfractionated heparin, warfarin, or aspirin (Grade: 1B)

LMWH is recommended in preference to the remaining agents irrespective of mechanical compressive devices (Grade: 2B)

Recommendation for the use of mechanical compressive devices for minimum of 10–14 days rather than no prophylaxis (Grade: 1C)

Patients undergoing hip fracture surgery

Recommendation for the use of chemoprophylaxis for minimum of 10–14 days with one of the following: LMWH, fondaparinux, low-dose unfractionated heparin, warfarin, or aspirin (Grade: 1B)

LMWH is recommended in preference to unfractionated heparin or fondaparinux irrespective of mechanical compressive devices (Grade: 2B)

LMWH is recommended in preference to warfarin or aspirin irrespective of mechanical compressive devices (Grade: 2C)

Recommendation for the use of mechanical compressive devices for minimum of 10–14 days rather than no prophylaxis (Grade: 1C)

Patients undergoing major orthopedic surgery and receiving LMWH

Recommendation for the initiation of LMWH either ≥12 h preoperatively or ≥12 h postoperatively (Grade: 1B)

Patients undergoing major orthopedic surgery

Recommendation for concomitant systemic chemoprophylaxis and intermittent pneumatic compression devices throughout hospitalization (Grade: 2C)

Recommendation against the use of IVC filter in patients with contraindications to both mechanical and systemic prophylaxis (Grade: 2C)

Recommendation against the use of postoperative duplex ultrasound screening prior to discharge from hospital (Grade: 1B)

Patients undergoing major orthopedic surgery and high risk of bleeding

Recommendation for the use of intermittent pneumatic compression devices in the place of systemic chemoprophylaxis (Grade: 2C)

Patients undergoing major orthopedic surgery who are noncompliant with injections or intermittent pneumatic compression devices

Recommendation for the use of oral apixaban or dabigatran (rivaroxaban or warfarin if not available) (Grade: 1B)

Summary of the 2012 American College of Chest Physician’s clinical practice guidelines for the prophylaxis of venous thromboembolism in orthopedic patients. Grade 1 is a strong recommendation, whereas Grade 2 equates to a weak recommendation. The qualifiers A, B, and C pertain to the basis for the recommendations being high, moderate, or low-quality evidence respectively.

The Surgical Care Improvement Project (SCIP) guidelines [45] are a series of core measures aimed to reduce surgical complications. It is essential that surgeons adhere to these guidelines because they are a measure of quality with respect to hospital care. The guidelines, which are based on the ACCP guidelines, were recently revised in 2014, with one of the core measures being appropriate VTE prophylaxis initiated within 24 h before or after surgery.

Duration

As mentioned previously, the AAOS guidelines did not include specific recommendations for the duration of prophylaxis due to the scant number of placebo-controlled randomized trials. However, the ACCP guidelines recommend a minimum of 10–14 days of prophylaxis and suggest that 35 days should be considered [44]. Additionally, recent systematic reviews recommend extended prophylaxis of up to 28–35 days in patients undergoing total hip arthroplasty, as this has been shown to decrease the risk of post discharge VTE. Extended prophylaxis should also be considered in high-risk patients with known risk factors for VTE [46, 47].

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