Venous thromboembolism (VTE), specifically pulmonary embolism (PE), is the most common cause of death and one of the most common reasons for readmission unrelated to the surgical site after elective total hip replacement (2,3,4,5,6,7,8,9,10,11). While administrative databases have recently drawn attention to inpatient PE after total hip arthroplasty (THA) and total knee arthroplasty (TKA), nearly 85% of all PE following total hip replacement occur after hospital discharge (5). Collectively, elective THA and TKA are the most commonly performed procedures in the United States, totaling nearly 1 million annually with slightly more than 300,000 cases involving the hip (7,12,13). Moreover, they are increasing in number with the aging of the baby boomer generation and constitute the single largest class of procedures covered by Medicare. Yet, despite advancements in surgical and perioperative care, fatal PE occurs in 0.1% to 0.5% of patients and is responsible for more than 1,000 patient deaths each year following these elective operations (14,15,16). Appropriately, considerable effort has been directed at identifying the optimal method to prevent thromboembolic disease in this patient population. However, use of potent anticoagulants in the perioperative period to mitigate the propensity for activation of thrombogenesis after musculoskeletal operations must necessarily be tempered by consideration of the bleeding risk following major orthopedic procedures where hemostasis is imperfect in the setting of exposed bony surfaces. Orthopedic surgeons typically opt for a perioperative thromboprophylaxis regimen that minimizes bleeding risk, while medical practitioners more often prioritize the absolute reduction of thromboembolic events. Accordingly, recommendations of professional associations have historically disagreed on the matter of VTE prophylaxis and, consequently, the ideal prophylaxis is yet to be determined (17,18). It will undoubtedly represent a risk–benefit balance between the fear of fatal PE and respect for the morbidity of hematoma (19,20,21) and secondary infection resulting from bleeding associated with perioperative anticoagulant use.

Superimposed on this backdrop of controversy around VTE prophylaxis, we now also appreciate that there is a unique propensity for VTE after orthopedic procedures that is largely attributable to activation of the clotting cascade by intravasation of marrow fat into the bloodstream. Instrumentation of the intramedullary canal and pressurization during cementation of the femoral component in THA, combined with intimal injury to the femoral vein, are thought to be responsible for the particularly dramatic predilection for PE that was observed to occur early in the evolution of this operation. As noted by Charnley, the seriousness of this complication is underscored by the possibility of a fatal embolic event following THA despite its successful technical performance. Over the ensuing four decades since the popularization of hip replacement, many technical advances have improved the reliability, safety, and durability of the procedure but the risk of deep vein thrombosis (DVT) and PE persists. In a series of 7,959 THAs performed from 1962 to 1973, Johnson et al. (6) reported an overall PE incidence of 7.89% with fatal PE observed in 1.04% of patients. Since that time, considerable effort has been expended in better understanding the pathophysiology of thromboembolic disease after THA, and even more has been devoted to optimizing its prevention. Accordingly, this chapter will focus on current concepts of VTE, as well as contemporary methods for its prevention.

DVT is the most common manifestation of thromboembolic disease as a precursor of PE. Historically, in contrast to TKA, the most prevalent form of DVT after total hip replacement was thrombosis in the femoral vein that was segmental in nature and discontinuous with any clot located more distally in the calf. Proximal thrombi, specifically segmental clots in the femoral vein at the level of the lesser trochanter, predominate after THA and are likely initiated
by intimal injury resulting from torsion of the vein during femoral preparation (Fig. 29.1). Such injury has been shown to occur regardless of surgical approach (22). Traditionally, PE was diagnosed by pulmonary arteriography but is now most sensitively identified by multiplanar CT of the chest (Fig. 29.2), which has arguably resulted in overdiagnosis of clinically insignificant subsegmental peripheral thrombi (23). The prevalence of PE is difficult to quantify and its clinical importance is difficult to ascertain, but in the general population the frequency of autopsy-proven fatal PE is 2.5 times that of symptomatic nonfatal PE.

Moreover, DVT may be solely responsible for other morbidity related to chronic venous insufficiency. Five years after surgery, signs and symptoms of postthrombotic syndrome were found in 67% of patients with asymptomatic, venographically confirmed postoperative DVT, compared with 32% of patients who had a negative postoperative venogram (24). Yet, reports of clinically important postthrombotic syndrome are rare among orthopedic centers performing large numbers of hip replacements. Postthrombotic morbidity is more common after idiopathic spontaneous DVT than after provoked postoperative DVT (24) probably because thrombosis in the latter circumstance is more commonly nonocclusive and flow past the thrombus is maintained.

Historically, the risk of DVT in an unprotected patient was 70% to 84% after THA or TKA; the risk of symptomatic PE approached 15%, and the risk of fatal PE was 1% to 3.4% (3,25). Coventry et al. (3) reported a 3.4% fatal PE rate after 2,012 consecutive THAs from 1969 to 1971; the average duration of surgery was 2.4 hours and the average blood loss was 1,650 cc. These patients were on bed rest for 1 week and the mean postoperative hospital stay was 3 weeks. Since that time, the incidence of DVT after total joint arthroplasty has been substantially reduced. The observed decrease is widely accepted as being attributable to the implementation of several pharmacologic and mechanical prophylactic regimens as well as improved techniques of anesthetic management and technical advances in the operation itself (26,27). Data from two studies with a 3- to 6-month follow-up revealed a fatal PE rate as low as 0.12% to 0.35% in 4,594 patients who underwent THA without any type of chemoprophylaxis (28,29). Compared with patients in earlier studies, these patients benefited from more rapid postoperative mobilization and a shorter length of hospital stay. While the reduction in PE events is welcome news for patients, the rarity of fatal PE increases the difficulty implicit in demonstrating a statistically convincing reduction in the event rate with any one regimen as compared with another. With further decreases in the likelihood of fatal PE, it will be necessary to balance the incremental benefit of eliminating PE by using potent anticoagulants against the risk of bleeding complications induced by these anticoagulants (29). For example, in 1977 Johnson et al. (6) reported a 1.68% overall perioperative mortality after 7,959 THAs, in the absence of VTE prophylaxis. Two later studies involving a total of 12,769 patients undergoing THA found a similar 1.71% overall mortality rate without VTE prophylaxis (27,28). While prophylaxis for VTE has been the standard of care since a 1986 NIH consensus conference on the subject (30), not surprisingly current methods of mitigation of VTE risk are as variable as the underlying perceptions of its prevalence.

Routine prophylaxis for VTE after THA or TKA became the standard of care in North America after it was recommended by the National Institutes of Health (NIH) Consensus Conference in 1986 (30). Low-intensity warfarin has been the agent most commonly used by orthopedic surgeons during the subsequent three decades (31,32,33). Although warfarin use has considerably reduced the incidence of DVT, screening venography reveals asymptomatic venous system thrombi in 15% to 25% of patients after THA and in 35% to 50% after TKA. A similarly smaller reduction in venographic DVT after TKA than after THA has been observed with the use of newer anticoagulant agents (26). The overall risk of DVT is two to three times greater after TKA than after THA with the use of current prophylactic agents (26). The frequency of clinically significant bleeding events in patients treated with warfarin was found to be reduced with acceptance of low-intensity anticoagulation; the frequency was 8% to 12% when a prothrombin time index of 2.0 was routinely targeted, but it was 1% to 2% when the targeted prothrombin time index was 1.3 to 1.5 (International normalized ratio [INR] 2.0 to 2.5) (34). Although these data suggest that VTE is more refractory to standard prophylaxis after TKA than after THA, 85% to 90% of thrombi after TKA occur below the venous trifurcation in the deep calf veins, and the immediate risk of embolization is much smaller (25). In contrast, the distribution of DVT after THA historically was 40% proximal and 60% distal (3,26). It has been reported for
newer prophylactic agents that fewer than 10% thrombi after THA are located proximal to the trifurcation, with the remainder occurring in the calf (35). Because 85% to 90% of all DVTs after lower extremity total joint replacement occur in the calf when current prophylaxis is used, greater attention is being given to distal thrombotic disease. Longitudinal surveillance studies found that 17% to 23% of these distal thrombi extend to the more proximal veins of the thigh, where they acquire considerable embolic potential (36,37). The relationship between asymptomatic nonocclusive calf clots and late postthrombotic syndrome appearing as chronic venous insufficiency is unclear, but the considerable embolic potential of postoperative calf thrombi suggests that anticoagulant therapy with extended
prophylaxis should be continued for several weeks after surgery (35). DVT in the calf was reported to have a proximal propagation rate of almost 25% in general surgical patients, and symptomatic PE was reported in as many as 31% of patients with untreated deep calf thrombosis after total hip replacement (36,37). Conversely, spontaneous calf DVT in a patient who is ambulatory and has not recently undergone a surgical procedure is unlikely to be a precursor of pulmonary embolism.

Knowledge concerning the mechanisms of venous thrombosis and patient predisposition to this condition has paralleled our increased understanding of the basic science of coagulation. Fueled by the same information, the relative risks and benefits of prophylaxis, the choice and duration of specific agents in the face of abbreviated hospitalization, the role of routine diagnostic surveillance, and guidelines for treatment of established VTE have come under increasingly intense scrutiny.

Virchow’s triad, consisting of stasis, hypercoagulability, and damage to the intimal wall, remains the basis of our conceptual understanding of the mechanism of coagulation. Even the slightest of perturbations in the elements of this triad are responsible for abnormalities of thrombosis after musculoskeletal injury, disease, or surgery. Recent discoveries and improved understanding of the clotting cascade form the basis of new therapeutic approaches to preventing and treating thrombotic disease (Fig. 29.3).