**4. Prevention**

Clinical VTEs occur due to many different causes, but one significant factor is inadequate prophylaxis (Amin et al., 2010). Several barriers exist for inadequate prophylaxis. These include: expense, bleeding concerns, availability of agents, and conflicting recommendations. The American College of Chest Physicians (ACCP) and the American

The coagulation cascade is a complex system in which multiple components are activated to produce fibrin. An overview of the system along with the targets of various therapeutic interventions is shown in Figure 1. The coagulation pathway is separated into the intrinsic and the extrinsic pathways. The latter is activated in response to specific tissue injury. Both lead to the eventual formation of thrombin. Thrombin causes the conversion of fibrinogen to fibrin. Additionally, it activates factor XIII which stabilizes the fibrin. An endogenous fibrinolytic system balances this system. It consists of antithrombins, proteins C and S, and

Cell

Xa <sup>X</sup> VIIa

Fig. 1. Targets for anticoagulant drugs. LMWH = low-molecular-weight heparin. (Reference:

The primary pathophysiology factors that predispose any patient to VTE are the Virchow's Triad: endothelial injury, venous stasis (or turbulent blood flow), and hypercoagulability. Endothelial injury can occur due to manipulation, and retractor placement during surgery. Venous stasis can occur due to positioning and the use of a tourniquet. Hypercoagulability can occur as a result of depletion or dilution of endogenous anticoagulants. It is also associated with several pro-coagulant disease processes such as factor V Leiden deficiency,

The natural history of venous thromboembolism is variable. There are four potential outcomes when thrombosis occurs. The thrombus can propagate, embolize, organize, or undergo fibrinolysis. Proximal thrombi are more likely to propagate and embolize than the smaller distal thrombi in general. 80% of symptomatic DVTs involve the proximal veins

Clinical VTEs occur due to many different causes, but one significant factor is inadequate prophylaxis (Amin et al., 2010). Several barriers exist for inadequate prophylaxis. These include: expense, bleeding concerns, availability of agents, and conflicting recommendations. The American College of Chest Physicians (ACCP) and the American

IXa <sup>V</sup>

IIa

II

Hoffman M, Dougald M. The action of high-dose factor VIIa in a cell-based model of

Va

Va Tissue Factor

IX

VIIa

X

VIIIa

Xa

VII

II

Va

IIa

Platelet Activated Platelet

**3. Pathophysiology** 

the plasmin-plasminogen system.

Xa Inhibitors Heparin/LMWH Warfarin Direct Thrombin Inhibitor

VIIIa

XI

hemostasis. *Disease a Month* 2003; 49: 14-21)

protein C and S deficiency, and others.

(Conduah & Lieberman, 2007).

**3.1 Natural history** 

**4. Prevention** 

vWF

XIa

VIII

Academy of Orthopaedic Surgeons (AAOS) have each released separate guidelines regarding the prevention of VTE. This can be confusing to the providers.

Controversies exist regarding the two major practice guidelines for VTE prophylaxis. The ACCP has been updating its recommendations every 3 years for over 25 years (Hirsh et al., 2008). The AAOS guidelines have been a more recent development. Though the two have many similarities, there are a few significant differences. A major area of disagreement involves the use of DVT as a surrogate for PE in arthroplasty patients. The AAOS guidelines do not emphasize the correlation between DVT and pulmonary embolism (Eikelboom et al., 2009). In fact, the AAOS guidelines are for the prevention of PE following joint arthroplasty. The ACCP recommendations focus on the prevention of both VTE and PE as the goal rather than PE alone in the AAOS guidelines. Both guidelines focus on a balance between the risk of bleeding and the efficacy of anticoagulation. They both define risk-to-benefit ratio for different agents. Some of the most clinically relevant differences between the two guidelines are presented in Table 1. Neither guideline has been universally accepted. A recent survey was conducted by the American Association of Hip and Knee Surgeons regarding the practice standards among its member surgeons. The data demonstrated that 74% of the hospitals had adopted the ACCP guidelines, while 68% of the surgeons preferred the AAOS guidelines (Markel et al., 2010).

Furthermore, compliance with the current guidelines has been suboptimal. Many surgeons continue to under-appreciate the prevalence of VTE and remain concerned with postoperative bleeding. Additionally, patient factors can inhibit appropriate prophylactic treatment. Injectable agents are expensive. Moreover, some patients are not at ease or in compliance with their administration. Oral agents have the challenges including: titration, monitoring, and drug-drug, or drug-food interaction (Moyer et al., 2009).

#### **4.1 Extended duration prophylaxis**

The ACCP guidelines recommend the optimal duration of VTE prophylaxis to be 28 to 35 days following THAs, and 10 to 14 days following TKAs (Kolb et al., 2003). Currently, the mean length of hospital stay is between 3 to 4 days, therefore full compliance with this recommendation is difficult for both the patient and the provider. Several studies have reported that continuation of thromboprophylaxis beyond the hospitalization is efficacious and safe in the risk reduction of late VTE in surgical patients (Planes et al., 1996; Lassen et al., 1998; Comp et al., 2001; Bergqvist et al., 2002; Rasmussen et al., 2006).

Extended duration prophylaxis for VTE requires proper selection of pharmacological agent(s). The ideal anticoagulant should have the following characteristics: standard dosing with self-administration, no requirement for monitoring, established efficacy and safety profiles, acceptable tolerability in populations with co-morbid conditions, and few drugdrug or drug-foot interactions. The ACCP guidelines currently recommend warfarin, lowmolecular weight heparins (LWMH), and fondaparinux. They specifically recommend against using aspirin alone in the high-risk orthopedic patient population as there are insufficient evidence-based data.

The AAOS guidelines recommend 2 to 6 weeks of prophylaxis with warfarin, 6 weeks using aspirin, or 7 to 12 days using LMWH or fondaparinux (AAOS 2007). The ACCP guidelines,

Venous Thromboembolism in Orthopaedic Surgery 163

Variable;

Fixed;

Fixed;

Fixed; Once

Table 2. Comparison of warfarin to new oral anticoagulants. (Reference: Eikelboom JW. Weitz JI. A replacement for warfarin: the search continues. *Circulation* 2007;116:131-133.)

Mechanical prophylaxis using sequential compressive devices (SCDs) or foot pumps can be used as a sole means of VTE prophylaxis. Their clinical efficacy and safety have been documented in multiple studies. This is particularly useful in a patient that is perceived to have an elevated bleeding risk (Geerts et al., 2008). In many practices, mechanical devices are often used in conjunction with pharmacological prophylaxis. Newer devices may be used in the outpatient setting upon hospital discharge. The clinical efficacy, safety, and compliance have been documented in a few studies. It is necessary to continue to follow larger cohorts of patients using outpatient mechanical prophylaxis alone to fully determine

Warfarin has been used as VTE chemoprophylaxis in high-risk orthopedic patients for decades. It is an efficacious agent. However, it requires close monitoring. It can be both difficult and costly in the outpatient setting (Eikelboom & Weitz, 2007). It also has numerous drug-drug and drug-food interactions. These interactions can be particularly challenging considering the issue of poly-pharmacy in the elderly joint arthroplasty patient population. It also has a delayed onset of action, which may require bridging with a shorter acting anticoagulant such as LMWHs or unfractionated heparin. A recent paper by Caprini et al. noted that physicians often used inadequate bridging protocols in the postoperative period. This can have important clinical implications. They found that the 30-day mortality rate was

The ACCP guidelines do not recommend using aspirin alone in any of the high-risk orthopedic patient populations. The AAOS guidelines do sanction its use in patients with

This has been included in the ACCP guidelines for patients undergoing general surgery procedures. However, the ACCP guidelines have recommended against using

found to be 6% for DVT and 12% for PE in this cohort (Caprini et al., 2005).

standard risk profile for pulmonary embolism prevention (Geerts et al., 2008).

Warfarin Vitamin K

Apixaban Factor Xa

Rivaroxaban Factor Xa

Dabigatran etexilate

**4.3.1 Mechanical** 

the efficacy and compliance.

**4.3.2 Warfarin** 

**4.3.3 Aspirin** 

**4.3.4 Unfractionated heparin** 

antagonist

Factor IIa inhibitor

inhibitor

inhibitor

**Drug Mechanism Dosing Monitoring Half Life Renal Clearance**

Twice Daily No 14-17

Twice Daily No 9-14

Daily Yes 40 hours 0%

Daily No 9 hours 65%

hours 100%

hours 25%

in contrast, recommend pharmacological thromboprophylaxis for up to 35 days after THA and for 10 to 35 days after TKA. Moreover, they recommend against the use of aspirin in this patient population.


Table 1. Summary of ACCP and AAOS recommendations for pharmacologic thromboprophylaxis in patients undergoing elective hip or knee surgery. (Reference: Huo M. VTE prophylaxis after total joint arthroplasty: current challenges-potential solutions. *Current Orthopaedic Practice* 2011;22:193-197.)
