INTRODUCTION — In adults undergoing major orthopedic procedures of the lower extremity, the risk of postoperative venous thromboembolism (VTE; lower extremity deep venous thrombosis, pulmonary embolism) is among the highest of all surgical procedures. Major orthopedic surgeries are considered the following:
●Hip replacement surgery (eg, total or partial hip arthroplasty)
●Knee replacement surgery (eg, total or partial knee arthroplasty)
●Hip fracture surgery (including open reduction, internal fixation)
Our approach to management of adults undergoing major orthopedic surgery, all of whom are at high risk for VTE, is reviewed in this topic and is for the most part consistent with the American College of Chest Physicians and the American Society of Hematology recommendations [1,2].
VTE prevention in the following patient populations is not covered in this topic but is discussed elsewhere:
●VTE prevention in adults undergoing orthopedic surgery who are at low risk for VTE – (See "Prevention of venous thromboembolism (VTE) in adults undergoing non-major extremity orthopedic surgery".)
●Nonorthopedic surgical patients – (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients".)
●Pelvic ring fracture/hip fractures related to severe trauma – (See "Severe pelvic fracture in the adult trauma patient" and "Venous thromboembolism risk and prevention in the severely injured trauma patient".)
●Multiple lower extremity fractures from severe trauma – (See "Severe lower extremity injury in the adult patient" and "Venous thromboembolism risk and prevention in the severely injured trauma patient".)
●Hospitalized medical patients – (See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults".)
RISK ASSESSMENT — In patients undergoing major orthopedic surgery including total or partial hip arthroplasty, total or partial knee arthroplasty, and hip fracture surgery (eg, open reduction, internal fixation), we assess the risk of postoperative VTE, as well as postoperative bleeding, to select the optimal method of thromboprophylaxis. Indications for these surgeries are described separately.
●(See "Hip fracture in adults: Epidemiology and medical management" and "Total hip arthroplasty" and "Complications of total hip arthroplasty", section on 'Venous thromboembolism'.)
●(See "Total knee arthroplasty" and "Complications of total knee arthroplasty", section on 'Thromboembolism'.)
●(See "Hip fracture in adults: Epidemiology and medical management".)
Risk of thrombosis — Major orthopedic procedures carry a high baseline risk for symptomatic VTE (approximately 4 to 5 percent), which can be increased further by the presence of additional procedure- and patient-related factors. Among all surgical patients, those undergoing major lower extremity orthopedic surgery are considered to have the highest baseline VTE risk. We do not use the Caprini score to assess VTE risk, since the score was validated in patients undergoing nonorthopedic surgery, and by default, all patients undergoing major orthopedic surgery are designated as high thrombotic risk [3]. (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients", section on 'Thrombosis risk model (Caprini)'.)
In the past, baseline rates of VTE in patients undergoing major orthopedic surgery who were not receiving thromboprophylaxis were reported to be as high as 30 percent; however, later data have reported rates less than 5 percent [1,4,5]. The American College of Chest Physicians (ACCP) has estimated the baseline perioperative, 35-day risk at 4.3 percent, with the highest risk occurring in the first 7 to 14 days (1.8 percent for symptomatic deep venous thrombosis [DVT] and 1 percent for pulmonary embolism [PE]) and lower rates in the subsequent 15 to 35 days (1 percent for symptomatic DVT and 0.5 percent for PE) [1].
Additional procedure- and patient-related risk factors that can further augment the risk of VTE in this population include the following:
●Procedure-related factors:
•Greater extent and longer duration of surgery
•General anesthesia (as opposed to spinal anesthesia)
•Prolonged period of immobilization and/or casting postoperatively
•Bilateral total joint arthroplasty (as opposed to unilateral arthroplasty)
●Patient-related factors (see "Overview of the causes of venous thrombosis"):
•General patient-related factors that can contribute to VTE risk in all surgical patients are listed in the table (table 1).
•Patient-related factors that are specific to those undergoing major orthopedic surgery include age >75 years (particularly ≥85 years), poor ambulation (prior to surgery), obesity, and cardiovascular disease [6-10].
Pathogenetic factors that may contribute to the particularly high risk in this group include compression of the deep veins from positioning of the extremity during hip surgery (eg, flexion and adduction of the hip) and possibly the use of a thigh tourniquet during knee surgery [6,11-13]. (See "Total knee arthroplasty", section on 'Tourniquet use'.)
Risk of bleeding — In estimating the risk of bleeding, the clinician should consider surgical- and patient-related factors:
●Factors attributable to surgery – Most experts consider patients undergoing major orthopedic surgery to have a high baseline risk of bleeding (2 to 4 percent) (table 2). Although the risk of bleeding is high relative to other surgical procedures, in most cases, the risk is not so high as to preclude use of pharmacologic thromboprophylaxis unless the patient has a contraindication.
Estimates of the baseline risk of bleeding in the absence of thromboprophylaxis in orthopedic patients have been hampered by factors, including derivation of data from heterogeneous populations, increasing use of thromboprophylaxis, improved surgical techniques, and use of adjunctive agents to limit bleeding (eg, tranexamic acid) (see "Total hip arthroplasty", section on 'Minimizing blood loss' and "Total knee arthroplasty", section on 'Minimizing perioperative blood loss'). Nonetheless, the ACCP and others have estimated that the average untreated bleeding risk in nontrauma patients is <2 percent [1,14], suggesting that the influence of postoperative pharmacologic thromboprophylaxis has minimal effect on the risk of bleeding. However, rates are likely underestimated by the inclusion in trials of only those patients with a low risk of bleeding, such that the true rate is likely higher than 2 percent.
●Additional patient-related risk factors – Since there are no tools available to assess the risk of bleeding in this population, we obtain a full history and examination to assess the risk of major bleeding. Major bleeding is typically defined as fatal bleeding, symptomatic bleeding in a critical area or organ, bleeding causing a fall in hemoglobin of ≥2 g/dL or leading to transfusion of two or more units of whole blood or red cells, and/or bleeding requiring reoperation [15]. (See "Venous thromboembolism risk and prevention in the severely injured trauma patient".)
The risk of major bleeding is generally considered unacceptably high if any of the following are present (table 3):
•Active, clinically significant bleeding (epistaxis and menstrual bleeding are not contraindications to pharmacologic thromboprophylaxis).
•Intracranial hemorrhage.
•Central nervous system tumor.
•Severe coagulopathy or bleeding diatheses.
•Platelet count <50,000/microL.
•A condition in which bleeding is potentially catastrophic (eg, bleeding into a major organ, eye, or pericardial space).
•Anticipated or recent neuraxial anesthesia. The timing of neuraxial anesthesia relative to use of anticoagulation or antiplatelet medication is presented separately. (See "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication".)
Elective or semielective surgery in patients with conditions that contraindicate anticoagulation can be delayed until the condition is under control (eg, control hypertension, improve platelet function, treat coagulopathy). For those surgeries that must proceed, patients are managed with mechanical prophylaxis alone until the risk of bleeding becomes acceptably low. (See 'Patients with unacceptably high bleeding risk' below.)
APPROACH TO PHARMACOLOGIC THROMBOPROPHYLAXIS (LOW-RISK BLEEDING) — For patients undergoing major lower extremity orthopedic surgery (eg, hip fracture surgery, total or partial hip arthroplasty, total or partial knee arthroplasty) who are at low risk of bleeding, we recommend pharmacologic thromboprophylaxis with or without intermittent pneumatic compression (IPC) devices rather than no thromboprophylaxis. Patients who have contraindications to pharmacologic thromboprophylaxis (table 3) should receive mechanical prophylaxis alone until the contraindication resolves. Risk of bleeding and mechanical prophylaxis are discussed separately. (See 'Risk of bleeding' above and 'Patients with unacceptably high bleeding risk' below.)
The clinician should be aware that any form of thromboprophylaxis reduces but does not eliminate the risk of VTE entirely. In addition, thromboprophylaxis has a greater impact on reducing the rate of asymptomatic rather than symptomatic events and has minimal effect on mortality. This is particularly true in patients with the highest risk of VTE (eg, patient undergoing total hip arthroplasty who has active cancer).
Choosing an agent — Our general approach to choosing an agent for pharmacologic thromboprophylaxis in patients undergoing major lower extremity orthopedic procedures who are at low risk of bleeding is influenced by the type of surgery and comorbidities (algorithm 1):
●First-line agents for patients undergoing total hip or total knee arthroplasty – For most patients undergoing hip or knee arthroplasty, we suggest low molecular weight (LMW) heparin or a direct oral anticoagulant (DOAC) as the initial agent in the early perioperative period (ie, up to 14 days). Enoxaparin or dalteparin are LMW heparin agents that are well studied and commonly used. Among the DOACs, we prefer rivaroxaban or apixaban rather than dabigatran or edoxaban since there are more data to support their use in this setting. Dosing and efficacy of these agents are discussed below. (See 'Low molecular weight heparin' below and 'Direct oral anticoagulants' below.)
●First-line agent for patients undergoing hip fracture surgery – For most patients undergoing hip fracture surgery, we suggest LMW heparin as the preferred agent for the entire duration of prophylaxis (ie, up to 35 days). We generally avoid DOACs in this setting since their safety and efficacy have not been studied in this population. (See 'Duration' below and 'Low molecular weight heparin' below.)
●Patients with renal failure – In patients with severe renal failure (eg, creatinine clearance <30 mL/min or on hemodialysis), unfractionated heparin (UFH) is the preferred agent; however, warfarin may be used if heparin injections are undesirable (target international normalized ratio 2 to 3). Patients with less severe renal insufficiency can receive dose-adjusted LMW heparin (table 4). Some DOACs can also be dose-adjusted. (See 'Unfractionated heparin' below and 'Warfarin' below and 'Low molecular weight heparin' below.)
●Patients with heparin-induced thrombocytopenia (HIT) – Patients with HIT or history of HIT should be treated with a nonheparin agent, the details of which are discussed separately. (See "Management of heparin-induced thrombocytopenia".)
●Role of aspirin – Although some experts use aspirin as the sole initial agent for thromboprophylaxis in the early postoperative period, we suggest not using this approach. However, in select patients who are considered at lower risk for VTE, we switch to aspirin following a short course of anticoagulant therapy (eg, 5 to 10 days of rivaroxaban or LMW heparin followed by aspirin for the remaining duration of thromboprophylaxis), as discussed below. (See 'Duration' below and 'Aspirin' below.)
Timing of initiation — The optimal timing of pharmacologic thromboprophylaxis in patients undergoing major orthopedic surgery is unknown. Practice is variable, depending on surgeon preference and the agent chosen.
●LMW heparin, UFH – Most experts agree that thromboprophylaxis with LMW heparin should not be administered close to surgery (eg, within four hours preoperatively and within four hours postoperatively). We prefer to start LMW heparin preoperatively with an initial dose ≥12 hours before surgery and then continue it postoperatively with a second dose ≥12 hours after surgery. Alternatively, LMW heparin can be started postoperatively with the first dose ≥12 hours after surgery. We use the same approach when using low-dose UFH.
This strategy is based upon trials that have suggested an unacceptably high bleeding risk when LMW heparin is given perioperatively (eg, within four hours of surgery) [16,17]. As an example, one randomized trial of patients undergoing total hip arthroplasty compared perioperative LMW heparin (dalteparin [started two hours before surgery], early postoperative LMW heparin [started four to six hours after surgery]), and postoperative warfarin (started in the evening on the day of surgery). Although rates of symptomatic VTE were lower in the perioperative and early postoperative LMW heparin groups compared with postoperative warfarin (1.5 and 3 versus 4.4 percent, respectively), rates of major bleeding were higher (9 and 7 versus 4 percent, respectively) [16].
●Oral agents – Oral agents such as DOACs and warfarin are generally started postoperatively 6 to 12 hours or more after surgery, provided that the patient can eat. However, if oral intake is expected to be delayed, then LMW heparin (or UFH) should be administered subcutaneously in the interim. Many patients also receive LMW heparin ≥12 hours before surgery, although the value of this practice is unknown.
●Fondaparinux - Fondaparinux is approved to start six or more hours after skin closure, consistent with major trials that demonstrated its efficacy. However, many experts administer the first dose 8 to 12 hours postoperatively to mitigate the bleeding risk, a practice that is also consistent with guidelines [1].
Duration — For most patients undergoing major lower extremity orthopedic surgery, we suggest that the initial thromboprophylaxis agent be continued for a minimum of 10 to 14 days (algorithm 2). Longer or shorter durations may be appropriate depending on the surgery and other risk factors:
●Hip arthroplasty – For patients undergoing hip arthroplasty, we suggest extending thromboprophylaxis for a total of 35 days. For most patients, the same agent is used for the entire 35-day course (typically LMW heparin or a DOAC). However, for select lower-risk patients, we suggest transitioning to aspirin after 5 to 10 days of initial therapy with LMW heparin or DOAC and completing the remainder of the 35-day course with aspirin alone. Lower-risk patients are considered as those who fill all of the following criteria: no other risk factors for VTE, no other indications for long-term anticoagulation, no lower limb or hip fracture in the previous three months, surgery is elective and unilateral, and the patient is ambulatory within 24 hours after surgery.
●Knee arthroplasty – For most patients undergoing knee arthroplasty, we suggest not extending thromboprophylaxis beyond 14 days, provided that the patient is fully ambulatory and discharged to home by the end of this period. For lower-risk patients (as defined above), we suggest transitioning to aspirin after five days of initial therapy with LMW heparin or DOAC and completing the remainder of the 10- to 14-day course with aspirin alone. For other patients, LMW heparin or DOAC prophylaxis is continued for the full 10- to 14-day course. In patients who are not yet ambulatory by 14 days, LMW heparin or DOAC prophylaxis is continued until fully ambulatory or 35 days, whichever is shorter.
●Hip fracture surgery – For patients undergoing hip fracture surgery, we suggest extending thromboprophylaxis for a total of 35 days. The same agent is used for the entire 35-day course (typically LMW heparin).
The practice of extending the duration of thromboprophylaxis beyond 10 to 14 days is supported by clinical trials and meta-analyses demonstrating that extended prophylaxis reduces the incidence of VTE without increasing the risk of major bleeding [18-33]. Most of these trials involved patients undergoing total hip arthroplasty. There are few data on patients undergoing hip fracture surgery, but it is reasonable to believe that extended prophylaxis would have similar benefits in this population. The benefits of extending thromboprophylaxis in patients undergoing total knee replacement are less certain. Two trials directly addressed this population and did not detect significant differences in rates of VTE with extended versus short-term thromboprophylaxis [26,34].
In a meta-analysis of six trials involving 2544 patients undergoing total hip (1795 patients) or knee arthroplasty (749 patients), extended thromboprophylaxis with LMW heparin for 28 to 42 days reduced the overall rate of VTE (3.7 versus 8.3 percent; relative risk [RR] 0.39, 95% CI 0.28-0.59) [33]. The rate of symptomatic VTE was also lower (2 versus 3.3 percent; RR 0.59, 95% CI 0.35-1.01), but the finding did not achieve statistical significance. There were more episodes of minor bleeding in the extended prophylaxis group, but rates of major bleeding were similarly low in both groups (0.2 versus 0.4 percent). Mortality was the same in both groups (0.4 percent).
Extended-duration thromboprophylaxis with DOACs appears to have similar benefit, though the available trials are limited to patients undergoing total hip arthroplasty [18-20,35]. In a trial involving 2509 patients undergoing total hip arthroplasty who were randomly assigned to extended thromboprophylaxis with a DOAC (rivaroxaban) for 31 to 39 days or short-term thromboprophylaxis with LMW heparin for 10 to 14 days, extended prophylaxis reduced both the overall rate of VTE (0.6 versus 5.1 percent) and the rate of symptomatic VTE (0.2 versus 1.2 percent) [18]. Mortality was low in both groups (0.2 versus 0.7 percent). There were more episodes of nonmajor bleeding in the extended prophylaxis group (6.5 versus 5.5 percent), but the rate of major bleeding was similarly low in both groups (one event in each).
The evidence supporting the practice of transitioning to aspirin after five days of pharmacologic thromboprophylaxis in select lower-risk patients is discussed below. (See 'Aspirin' below.)
It is uncertain whether courses shorter than 10 to 14 days can be used in select patients (eg, fast-track, short-stay patients). In one observational study of >17,000 patients undergoing fast-track total hip arthroplasty or total knee arthroplasty who had hospital length of stay <5 days and received thromboprophylaxis only while in the hospital, the VTE rate was 0.4 percent [36]. However, the data are preliminary and we suggest not routinely using a shortened course of thromboprophylaxis unless these findings are confirmed in prospective clinical trials.
Role of combined pharmacologic and mechanical thromboprophylaxis — While a combined strategy is unlikely to be harmful, there are no convincing data demonstrating a clear benefit. In addition, mechanical devices can be bothersome to many patients, particularly in the postoperative setting. Given the uncertainty of the additional benefit when added to pharmacologic prophylaxis, we generally do not insist upon their use. However, other centers may use them more routinely.
●In a post-hoc analysis of a randomized trial involving patients undergoing total knee arthroplasty that compared edoxaban and enoxaparin, there was a nonsignificant reduction in the incidence of VTE in patients who received concomitant anticoagulation and graduated compression stocking (GCS) compared with those who were anticoagulated without GCS (6 versus 13 percent) [37].
●In a small trial involving patients who underwent knee arthroplasty and were managed postoperatively with combined pharmacologic and mechanical prophylaxis, extending the use of mechanical prophylaxis to the outpatient setting reduced the rate of deep venous thrombosis (DVT) [38]. However, the events in this trial may not have been clinically significant, since most DVT were asymptomatic and all resolved within three months. In another trial involving patients undergoing total hip arthroplasty, six weeks of combined mechanical and pharmacologic prophylaxis (ie, IPC plus aspirin) did not significantly reduce rates of VTE compared with aspirin alone [39].
SPECIFIC AGENTS — Common agents that are used are discussed in this section. Investigational agents, such as milvexian (a factor XIa inhibitor), are discussed separately. (See "Investigational anticoagulants", section on 'Inhibitors of factor XI or factor XIa'.)
Low molecular weight heparin — Low molecular weight (LMW) heparin is a first-line agent for VTE prophylaxis in patients undergoing lower extremity major orthopedic surgery (eg, total or partial hip arthroplasty, total or partial knee arthroplasty, hip fracture surgery). Its efficacy is supported by multiple randomized trials that have demonstrated lower rates of symptomatic VTE and similar bleeding rates when compared with prophylactic-dose unfractionated heparin (UFH) or therapeutic anticoagulation with warfarin. (See 'Efficacy' below.)
Additional details of agent choice, timing, and duration are discussed above. (See 'Choosing an agent' above and 'Timing of initiation' above and 'Duration' above.)
Dosing — Our suggested dosing regimens below differ somewhat from product label recommendations but are generally consistent with 2012 American College of Chest Physicians guidelines on antithrombotic therapy and prevention of thrombosis [1]. Additional dosing options, including alternatives found in the labeling, are provided separately in the drug information monographs included with UpToDate. LMW heparin agents are renally cleared to varying degrees, and dose adjustment is advised for patients with renal insufficiency (table 4). LMW heparin is typically avoided in individuals with severe renal failure (eg, creatinine clearance <30 mL/min or on dialysis). Dose adjustment is also necessary for patients who have obesity (table 5).
Suggested dosing in patients without renal insufficiency who are not obese is as follows:
●Enoxaparin – For patients undergoing hip or knee arthroplasty or hip fracture surgery [40]:
•Hip arthroplasty and hip fracture surgery: 30 mg subcutaneously every 12 hours or 40 mg once daily started either ≥12 hours before or ≥12 hours after surgery.
•Knee arthroplasty: 30 mg subcutaneously every 12 hours started either ≥12 hours before or ≥12 hours after surgery. Some experts administer 40 mg once daily, either ≥12 hours before or ≥12 hours after surgery, although this dosing is based upon practice rather than data.
●Dalteparin – For patients undergoing total hip or total knee arthroplasty (off-label): 5000 units subcutaneously once daily started either ≥12 hours before or ≥12 hours after surgery [41,42]. If the initial dose is administered within four to eight hours of surgery (which is not our suggested approach), the United States product labeling recommends using one-half of the initial dose (2500 units) followed by the usual maintenance dose thereafter.
●Tinzaparin – For patients undergoing total hip or total knee arthroplasty: 4500 units subcutaneously once daily started either ≥12 hours before or ≥12 hours after surgery [43,44]. Tinzaparin is not available in the United States.
●Nadroparin – For patients undergoing total hip or total knee arthroplasty: 38 units/kg subcutaneously once daily (maximum: 3800 units) starting either ≥12 hours before or ≥12 hours after surgery; on postoperative day 4, increase the dose to 57 units/kg once daily (maximum: 5700 units) [45]. Nadroparin is not available in the United States.
Efficacy — Clinical trials have evaluated the efficacy of LMW heparin compared with placebo, direct oral anticoagulants (DOACs), UFH, and warfarin:
●LMW heparin versus placebo – In randomized placebo-controlled trials performed in the 1980s to 1990s in patients undergoing total hip arthroplasty, total knee arthroplasty, and hip fracture surgery, LMW heparin consistently reduced the incidence of asymptomatic VTE by approximately 50 percent [46-50]. The effect on symptomatic events, pulmonary embolism (PE), and bleeding was inconsistently reported.
●LMW heparin versus DOACs – Data comparing LMW heparin and DOACs are discussed below. (See 'Direct oral anticoagulants' below.)
●LMW heparin versus warfarin – There have been several randomized trials and meta-analyses comparing LMW heparin with therapeutic warfarin in patients undergoing total hip arthroplasty and total knee arthroplasty but not hip fracture surgery [16,51-61]. Most trials confirm that LMW heparin reduces the VTE rate by approximately one-third compared with warfarin. While earlier studies reported more major bleeding events associated with LMW heparin, later studies that compared these agents in the context of extended thromboprophylaxis did not find important differences in the risk of bleeding [62].
●LMW heparin versus UFH – In patients undergoing major orthopedic surgery, several randomized trials and meta-analyses have reported that LMW heparin is more effective than prophylactic UFH (ie, 5000 units twice daily) and has similar bleeding rates [14].
In a meta-analysis of 64 trials of mixed medical and surgical patients (including >3000 patients undergoing hip or knee arthroplasty or hip fracture surgery), LMW heparin reduced the rate of asymptomatic deep venous thrombosis (DVT) compared with prophylactic UFH (20 percent relative risk reduction) without an increase in the risk of major bleeding [14]. This effect was consistent among the subgroups of total hip arthroplasty, total knee arthroplasty, and hip fracture surgery.
LMW heparin also appears to have similar efficacy compared with higher doses of UFH (eg, 7500 units every 12 hours) but with lower bleeding risk [63]. A comparison of LMW heparin and eight hourly regimen of low-dose UFH has not been adequately studied in orthopedic patients. However, one meta-analysis that included surgical patients, some of whom had orthopedic surgery, showed similar rates of VTE between 8 hourly and 12 hourly regimens of UFH [64]. (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients", section on 'Low-dose unfractionated heparin'.)
●LMW heparin versus aspirin – Most studies testing the efficacy of aspirin for thromboprophylaxis after major orthopedic surgery suggest that it is less effective than LMW heparin [65-69]. These data are discussed below. (See 'Aspirin' below.)
●LMW heparin versus fondaparinux – Studies comparing LMW heparin and fondaparinux are discussed below. (See 'Fondaparinux' below.)
●LMW heparin versus mechanical thromboprophylaxis – LMW heparin has been poorly studied in comparison with mechanical methods (intermittent pneumatic compression [IPC], venous foot pump [VFP] devices, graduated compression stockings [GCS]) [70-74]. In one randomized trial involving 1761 patients undergoing total knee arthroplasty, LMW heparin reduced the composite endpoint of DVT or death compared with GCS alone (0.9 versus 3.2 percent) [70]. However, most of the events in the composite outcome were episodes of asymptomatic distal DVT.
In another randomized trial of 274 patients undergoing total hip arthroplasty, there was a nonsignificant trend toward fewer proximal DVT in the LMW heparin group compared with those assigned to VFP alone (9 versus 13 percent) [73]. There were no major bleeding complications, but many patients (>20 percent) were intolerant of the VFP.
Direct oral anticoagulants — Several DOACs that inhibit either factor Xa (rivaroxaban, apixaban, edoxaban) or thrombin (dabigatran) are approved and are being increasingly used as an alternative to LMW heparin for VTE prophylaxis following major orthopedic surgery [75,76]. Together with LMW heparin, DOACs are a first-line agent for VTE prophylaxis in patients undergoing total hip or knee arthroplasty. We avoid their use in patients following hip fracture surgery because there are insufficient data in this population. On balance, evidence from meta-analyses of randomized trials involving patients undergoing total hip or knee arthroplasty suggests that DOACs have equivalent efficacy and safety when compared with LMW heparin. (See 'Efficacy' below.)
A key advantage of DOACs is that they avoid injections and monitoring associated with LMW heparin and warfarin, respectively. In addition, they can be used in patients with a history of heparin-induced thrombocytopenia (HIT). DOACs should be avoided in patients with severe renal insufficiency (eg, creatinine clearance <30 mL/min).
Additional details regarding agent choice, timing, and duration are discussed above. (See 'Choosing an agent' above and 'Timing of initiation' above and 'Duration' above.)
Dosing — Suggested dosing for individual DOACs are the following (see "Direct oral anticoagulants (DOACs) and parenteral direct-acting anticoagulants: Dosing and adverse effects"):
●Rivaroxaban – 10 mg once daily started 6 to ≥10 hours after surgery
●Apixaban – 2.5 mg twice daily started ≥12 hours after surgery
●Dabigatran – 110 mg given one to four hours after surgery and 220 mg once daily thereafter
Dosing in patients with obesity is unclear. The International Society on Thrombosis and Haemostasis suggests that for patients with a body mass index >40 kg/m2 or weight >120 kg, standard dosing for rivaroxaban and apixaban rather than other DOACs can be used in this population [77].
Efficacy — In the available randomized trials evaluating the efficacy of DOACs, rates of symptomatic DVT have generally been similar to or lower than LMW heparin [18-20,35,51,78-100]. While most analyses report no difference in rates of bleeding, some studies report a possible modest increase in bleeding risk with DOACs compared with LMW heparin. On balance, we believe the data suggest that the safety and efficacy of DOACs for the prevention of VTE are similar to LMW heparin.
●Meta-analyses of DOACs versus LMW heparin – In a meta-analysis of 22 randomized trials (32,159 patients) that compared the factor Xa inhibitors (eg, rivaroxaban, apixaban, edoxaban) with LMW heparin for VTE prevention following hip or knee arthroplasty, there were fewer symptomatic DVTs in the DOAC group (4 fewer events per 1000) but at the expense of an increased risk of bleeding (2 more bleeding events per 1000) [80]. One limitation of these data is that follow-up was incomplete in some of the trials. In addition, most trials that compared DOACs with enoxaparin used the lower dose of enoxaparin (40 mg daily rather than 30 mg twice daily), which may have led to overestimation of the efficacy (and bleeding risk) of DOACs relative to LMW heparin.
In a subsequent network meta-analysis, patients who received factor Xa inhibitors had a lower incidence of DVT compared with LMW heparin (odds ratio [OR] 0.45, 95% CI 0.35-0.57) without an apparent increase in the rate of bleeding (OR 1.21, 95% CI 0.79-1.90) [51].
A meta-analysis evaluating the direct thrombin inhibitor dabigatran, compared with LMW heparin, did not detect significant differences in rates of symptomatic VTE (relative risk [RR] 0.71, 95% CI 0.23-2.12) or clinically important bleeding (RR 1.12, 95% CI 0.94-1.35) [82].
●Studies of individual DOACs versus LMW heparin – Data comparing the individual DOAC agents with LMW heparin include the following:
•Rivaroxaban – Clinical trials involving patients undergoing total hip and total knee arthroplasty, but not hip fracture surgery, reported that rivaroxaban has similar or superior efficacy compared with LMW heparin [18,35,85-90]. Some trials showed a trend toward an increase in bleeding; however, this was not a consistent finding.
•Dabigatran – The efficacy of dabigatran has been evaluated in randomized controlled trials involving patients undergoing total hip and total knee arthroplasty but not hip fracture surgery (including REMODEL, RENOVATE, REMOBILIZE) [19,91-95]. A meta-analysis of these trials reported similar efficacy and safety of dabigatran when compared with LMW heparin [93].
•Apixaban – Randomized trials involving patients undergoing total hip and total knee arthroplasty report comparable rates of VTE between apixaban and LMW heparin without an increased risk of bleeding [20,101-103].
•Edoxaban – Data regarding the use of edoxaban for the prevention of VTE come from two randomized trials in Japanese patients undergoing total hip arthroplasty or total knee arthroplasty (STARS E-3 and STARS J-5) [96-98]. In a pooled analysis of the two trials, edoxaban lowered the incidence of VTE compared with LMW heparin (5.1 versus 10.7 percent) with a similar safety profile [104]. Edoxaban has not yet received regulatory approval for prevention of VTE in most countries.
●Studies comparing DOACs with one another – The different DOAC agents have not been directly compared with one another in head-to-head clinical trials. Studies comparing them indirectly using network meta-analysis methodology have reached variable conclusions [83,84,105]. In a network meta-analysis of data from six randomized trials that compared different DOACs with LMW heparin (apixaban in one trial [5395 patients], dabigatran in two trials [7400 patients], edoxaban in one trial [8240 patients], and rivaroxaban in two trials [8255 patients]), there were no important differences among the DOACs with regard to the risk of VTE [105]. The risk of major or clinically significant bleeding was lower with apixaban compared with rivaroxaban (RR 0.47, 95% CI 0.36-0.61), dabigatran (RR 0.69, 95% CI 0.51-0.94), and edoxaban (RR 0.54, 95% CI 0.41-0.69). Dabigatran was also associated with lower bleeding risk compared with rivaroxaban (RR 0.68, 95% CI 0.53-0.87) and edoxaban (RR 0.77, 95% CI 0.60-0.99).
●Studies of extended-duration thromboprophylaxis – Limited data of DOACs in the extended-duration setting (eg, for 35 days) suggest similar efficacy to DOACs administered for 10 to 15 days. Studies evaluating shorter versus longer duration of thromboprophylaxis are discussed above. (See 'Duration' above.)
●Studies comparing DOACs with agents other than LMW heparin – Studies comparing DOACs with other agents, such as aspirin (for extended prophylaxis) and fondaparinux, are discussed below (see 'Aspirin' below and 'Fondaparinux' below). DOACs have not been directly compared with warfarin or UFH.
●Studies in patients with HIT – The use of DOACs in patients with a history of HIT is discussed separately. (See "Management of heparin-induced thrombocytopenia", section on 'Direct oral anticoagulants'.)
Aspirin — The use of aspirin for thromboprophylaxis in patients undergoing major orthopedic surgery is best supported for select lower-risk patients as an extended-duration prophylactic agent following an initial 5- to 10-day course of anticoagulant prophylaxis (eg, LMW heparin or DOAC) [21,106]. We do not use aspirin as a sole initial agent during the early postoperative course.
When aspirin is used in this setting, the typical dosing is 81 mg once daily [107] or, less commonly, 160 mg once daily [108]. Higher doses do not appear to be more effective [109]. In the past, doses as high as 500 mg three times a day were used; however, adverse effects were unacceptably high with the higher dosing.
The efficacy of aspirin as a prophylactic agent is supported by randomized clinical trials [21,68,107,108,110]:
●Studies on transitioning to aspirin for extended prophylaxis in lower-risk patients – The largest trial evaluating the use of aspirin for extended thromboprophylaxis in patients undergoing major orthopedic surgery was the EPCAT II trial [21]. In this trial, 3424 patients who underwent total hip or total knee arthroplasty and who received initial thromboprophylaxis for five days with the DOAC rivaroxaban were then randomized to aspirin (81 mg) or rivaroxaban for ongoing thromboprophylaxis on subsequent days [21]. The duration of thromboprophylaxis depended on the surgery: Patients who underwent total knee arthroplasty received an additional nine days of therapy, and those who underwent total hip arthroplasty received an additional 30 days of therapy. Patients included in this trial were highly selected and included only those at the lower end of the spectrum of risk for VTE (ie, no other risk factors for VTE, no other indications for long-term anticoagulation, no lower limb or hip fracture in the previous three months, surgery was elective and unilateral, and patient was ambulatory within 24 hours after surgery). In this population, transitioning to aspirin after the initial five days resulted in similar rates of VTE (<1 percent) and major bleeding (<1 percent) compared with continued rivaroxaban. An earlier and smaller trial (EPCAT) in patients undergoing total hip arthroplasty reported similar findings [107].
There are no data on the use of aspirin for this purpose in patients undergoing hip fracture surgery.
●Studies on aspirin as the sole thromboprophylactic agent – Compared with no thromboprophylaxis, aspirin has been shown to reduce the incidence of symptomatic VTE in patients undergoing major orthopedic surgery, particularly hip fracture surgery, with a relative risk reduction of approximately 30 percent [108]. The efficacy of aspirin compared with anticoagulant thromboprophylaxis (LMW heparin, DOACs, warfarin, or UFH) in this setting is less certain, with most trials reporting inferior or similar efficacy [68,110].
•In a randomized crossover trial (CRISTAL) of 9711 patients, aspirin (100 mg orally per day) was compared with enoxaparin (40 mg subcutaneously per day) for 35 days after hip arthroplasty and 14 days after knee arthroplasty [69]. Enoxaparin was superior to aspirin in preventing symptomatic VTE (above- or below-knee DVT and PE) at 90 days (1.82 versus 3.45 percent). There was no difference in the rates of major bleeding (<0.5 percent) and death. The outcome was mostly driven by enoxaparin's superiority at preventing distal DVT (1.2 versus 2.4 percent) rather than proximal DVT (0.2 percent each) or PE (0.6 versus 1.1 percent). Interpretation is limited since the trial was stopped early for harm, hospitals were not blinded to treatment allocation, and 5 percent of patients were lost to follow-up.
•A meta-analysis of 13 randomized trials (6060 participants) that did not include the trial above compared aspirin with various anticoagulants (LMW heparin, rivaroxaban, warfarin) in patients undergoing total hip or total knee arthroplasty [110]. No significant difference in VTE rate (RR 1.12, 95% CI 0.78-1.62) or rate of major bleeding (RR 1.11, 95% CI 0.47-2.59) was reported. However, there was considerable heterogeneity between studies, which limits the certainty of the findings. In addition, the meta-analysis included the two trials discussed above (EPCAT and EPCAT II [21,107]), in which aspirin was not the sole agent, and did not include CRISTAL [69].
•Retrospective studies have reached variable conclusions regarding the efficacy of aspirin in this setting [111-114], with some reporting similar VTE rates in patients treated with aspirin compared with other agents [111], while others reported lower VTE rates in patients receiving aspirin [112,113]. However, data from retrospective studies are fundamentally limited since they are highly susceptible to selection bias (ie, aspirin is more often used in lower-risk patients), and thus firm conclusions cannot be drawn from these studies.
•In one older trial, warfarin administered for 21 days was also found to be superior to aspirin for the prevention of venographically detected DVT following hip fracture surgery (20 versus 41 percent) [115].
Second-line options — Second-line options include prophylactic-dose UFH, warfarin, and fondaparinux. Use of these agents for VTE prophylaxis in the setting of major lower extremity orthopedic surgery is generally limited to patients in whom LMW heparin and DOACs cannot be administered (eg, patients with severe renal insufficiency, cost prohibitive).
Unfractionated heparin — UFH is a second-line option that can be used in patients who cannot receive LMW heparin or DOACs (eg, due to renal failure). Choosing an agent is described above. (See 'Choosing an agent' above.)
It is given at a dose of 5000 units subcutaneously twice daily (less commonly, three times daily). In patients with obesity, the optimal dose is unknown and some experts use 7500 units twice daily, but data to support this regimen are limited [116,117]. No renal adjustment is necessary.
The efficacy of UFH in this setting was studied in randomized trials carried out in the 1970s to 1990s. In a meta-analysis of eight trials involving >500 patients undergoing hip arthroplasty, UFH reduced the incidence of DVT by 44 percent compared with no thromboprophylaxis (RR 0.53, 95% CI 0.32-0.89). Similar findings were noted in trials involving patients undergoing hip fracture surgery (RR 0.56, 95% CI 0.39-0.81; six trials) [1,14].
Trials demonstrating the inferiority of UFH compared with LMW heparin are described above. (See 'Low molecular weight heparin' above.)
Warfarin — Warfarin is a second-line agent for VTE prophylaxis following major orthopedic surgery. Its use is mostly limited to patients who cannot take DOACs or LMW heparin (eg, patients with severe renal insufficiency). Choosing an agent is described above. (See 'Choosing an agent' above.)
Typical dosing regimens for warfarin start at 5 mg orally once daily; occasionally, a lower or higher starting dose is warranted. Warfarin is started 12 to 24 hours after surgery (provided that the patient can eat) or the evening before surgery. While some experts adjust thereafter for a therapeutic target international normalized ratio (INR) of 1.5 to 2.5 [118-120], most experts adjust to target an INR of 2.5 (range 2 to 3). We use a validated warfarin dose adjustment nomogram since genotype-guided warfarin dosing does not offer any advantage over standard dosing regimens. (See "Warfarin and other VKAs: Dosing and adverse effects".)
Compared with no thromboprophylaxis, therapeutic anticoagulation with warfarin has been shown in older trials to reduce the incidence of asymptomatic VTE in patients undergoing major hip surgery, particularly hip fracture surgery, with a relative risk reduction of 55 percent [14,115,121]. In one trial, warfarin was also found to be superior to aspirin for the prevention of DVT following hip fracture surgery [115]. In addition, warfarin has been shown to be more effective than mechanical methods of thromboprophylaxis (eg, IPC devices) in most trials [122-125]. However, more recent clinical trials and meta-analyses report inferiority of warfarin compared with LMW heparin, as discussed above. (See 'Low molecular weight heparin' above.)
Whether low-intensity regimens are of similar efficacy to standard-intensity regimens is unclear. A randomized trial involving older patients (mean age 72 years) undergoing total hip or knee arthroplasty compared a low-intensity regimen of warfarin (target INR 1.8) with a standard-intensity regimen (target INR 2.5) [126]. There was no difference in the rate of VTE or major bleeding, but interpretation is limited due to its open-label design and the low proportion of patients who achieved the target INR. Until further data are available, we continue to target an INR of 2.5.
Fondaparinux — Fondaparinux, a factor Xa inhibitor, is a second-line agent for VTE prophylaxis in patients undergoing lower extremity major orthopedic surgery. It is an option in patients with HIT. Choosing an agent is described above. (See 'Choosing an agent' above.)
In this setting, fondaparinux is given at a dose of 2.5 mg subcutaneously once daily. Fondaparinux is contraindicated in patients who weigh <50 kg and avoided in those with renal insufficiency [127].
The efficacy of fondaparinux has been evaluated in randomized trials and meta-analyses [1,128-134].
●In a 2016 meta-analysis of 25 trials including 21,000 mixed medical and surgical medical patients (most were undergoing major orthopedic surgery), fondaparinux reduced the incidence of symptomatic VTE compared with placebo (0.2 versus 1.2 percent; RR 0.15, 95% CI 0.06-0.36) and increased the risk of major bleeding (1.2 versus 0.5 percent; RR 2.56, 95% CI 1.48-4.44) [131].
●In trials comparing fondaparinux with LMW heparin, rates of symptomatic VTE were similar in both groups (0.6 percent in each; RR 1.03, 95% CI 0.65-1.63; nine trials), but major bleeding events were more common with fondaparinux (2.5 versus 1.8 percent; RR 1.38, 95% CI 1.09-1.75; 11 trials) [131].
●Fondaparinux has also been compared with DOACs. Retrospective studies report that DOACs (rivaroxaban, edoxaban) resulted in lower rates of VTE and either a similar or improved safety profile when compared with fondaparinux [135,136].
Extended-duration thromboprophylaxis with fondaparinux was studied in a randomized trial of 656 patients undergoing hip fracture surgery [137]. Compared with a one-week treatment course, one month of fondaparinux reduced the incidence of symptomatic VTE (0.3 versus 2.7 percent). There was a nonsignificant trend toward an increase in major bleeding with extended therapy.
The use of fondaparinux in patients with HIT is discussed separately. (See "Management of heparin-induced thrombocytopenia", section on 'Fondaparinux'.)
PATIENTS WITH UNACCEPTABLY HIGH BLEEDING RISK — For patients with an unacceptably high risk of bleeding and/or contraindications to pharmacologic thromboprophylaxis (table 3), we suggest mechanical thromboprophylaxis. Among the options, we prefer intermittent pneumatic compression (IPC) devices. Vena cava filters should not be routinely used in this setting.
Mechanical methods are less effective than pharmacologic prophylaxis. Thus, it is important to switch to or add a pharmacologic agent as soon as hemostasis is assessed as adequate, bleeding risk becomes acceptably low, and/or the bleeding diathesis has been reversed. Mechanical methods are also frequently used in combination with pharmacologic methods, although there are limited data to support this practice. (See 'Approach to pharmacologic thromboprophylaxis (low-risk bleeding)' above and 'Role of combined pharmacologic and mechanical thromboprophylaxis' above.)
Mechanical prophylaxis — Mechanical prophylaxis devices are effective for reducing the risk of VTE in this population and are appropriate for patients who cannot receive pharmacologic prophylaxis [1]. However, mechanical prophylaxis alone is generally less effective with regimens that contain pharmacologic prophylaxis [122-125,138,139].
Devices — Options for mechanical thromboprophylaxis include IPC, graduated compression stockings (GCS), and the venous foot pump (VFP). We prefer IPC since there are more data supporting its use in orthopedic patients [1].
●IPC – Data supporting the use of IPC for the prevention of VTE in orthopedic surgical patients are limited and subject to bias due to lack of blinding and small numbers. Nevertheless, the available data suggest that IPC may reduce the incidence of VTE (symptomatic and asymptomatic) by as much as 50 percent compared with no prophylaxis.
Several small trials of patients undergoing total hip arthroplasty, total knee arthroplasty, or hip fracture surgery compared IPC with no thromboprophylaxis and, in general, demonstrated a reduction in the rate of deep venous thrombosis (DVT) [39,140-143]. As an example, in a randomized trial of 310 patients who underwent total hip arthroplasty, IPC reduced the rate of venographic DVT from 49 to 24 percent and proximal DVT from 27 to 14 percent [140]. It is noteworthy that the residual rates of DVT were still high despite mechanical prophylaxis. Studies that suggest inferiority of IPC compared with low molecular weight heparin or warfarin are discussed separately. (See 'Low molecular weight heparin' above and 'Warfarin' above.)
●GCS – Evidence to support the use of GCS is derived from indirect data in other surgical and medical patients; outcome associated with the use of GCS in those populations is mixed and associated with an increase in the risk of local skin complications. Only one small trial in orthopedic patients has been performed and showed a similar lack of benefit [144]. Nonetheless, they are frequently used in combination with pharmacologic methods in high-risk patients undergoing orthopedic surgery. (See "Prevention and treatment of venous thromboembolism in patients with acute stroke", section on 'Ineffective or unproven treatments'.)
●VFP – Several small studies suggest that VFP devices may be effective in reducing the incidence of VTE in patients undergoing major orthopedic surgery, although data are biased and have small numbers [145-150]. (See "Venous thromboembolism risk and prevention in the severely injured trauma patient".)
Placement and timing of devices — For patients in whom mechanical methods (IPC, GCS, VFP) are indicated, devices are typically placed on the patient just prior to the start of surgery and used continuously postoperatively until hospital discharge, ambulation, or pharmacologic thromboprophylaxis is initiated.
If a mechanical device cannot be applied to the operated lower extremity, it can be applied to the contralateral extremity to decrease the risk for DVT (up to 20 percent of DVT occur in the nonoperated leg) and may theoretically prevent DVT in both lower extremities.
Although most operating rooms have mechanical devices, compliance postoperatively may be poor [151,152]. However, portable battery-powered devices may improve compliance [153].
Adverse effects including skin breakdown and contraindications to device use are discussed separately. (See "Prevention of venous thromboembolic disease in adult nonorthopedic surgical patients", section on 'Intermittent pneumatic compression and venous foot pump'.)
No role for vena cava filters — Prophylactic inferior vena cava (IVC) filters should not be routinely used in this setting. The risks of IVC filter placement are unacceptably high relative to the risk of VTE in this population. (See "Placement of vena cava filters and their complications".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Superficial vein thrombosis, deep vein thrombosis, and pulmonary embolism" and "Society guideline links: Anticoagulation".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●The Basics topics (see "Patient education: Deep vein thrombosis (blood clot in the legs) (The Basics)" and "Patient education: Pulmonary embolism (blood clot in the lungs) (The Basics)" and "Patient education: Choosing a medicine for blood clots (The Basics)" and "Patient education: Taking medicines for blood clots (The Basics)")
●Beyond the Basics topics (see "Patient education: Deep vein thrombosis (DVT) (Beyond the Basics)" and "Patient education: Pulmonary embolism (Beyond the Basics)" and "Patient education: Warfarin (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Risk assessment – Patients undergoing major lower extremity orthopedic surgery (eg, total or partial hip arthroplasty, total or partial knee arthroplasty, hip fracture surgery) should be assessed for risk of venous thromboembolism (VTE; lower extremity deep venous thrombosis and pulmonary embolism) and risk of bleeding. (See 'Risk assessment' above.)
•Major lower extremity orthopedic surgery is associated with a higher risk of symptomatic VTE compared with most other surgeries, with an estimated incidence of approximately 4 percent. The risk is greatest in the first 7 to 14 days.
•The risk of major bleeding is also high relative to other surgeries, with an estimated rate of 2 to 4 percent.
•Additional individual risk factors for VTE (eg, previous VTE) and bleeding (eg, thrombocytopenia) can further increase the baseline risk. In most cases, the bleeding risk is not so high as to preclude use of pharmacologic thromboprophylaxis unless the patient has a specific contraindication (table 3).
●Patients at low risk of bleeding – For patients undergoing major lower extremity orthopedic surgery who are at low risk of bleeding, we recommend pharmacologic thromboprophylaxis with or without intermittent pneumatic compression (IPC) devices rather than no thromboprophylaxis (Grade 1B). The choice of initial agent is influenced by the type of surgery and comorbidities (algorithm 1):
•Patients undergoing knee or hip arthroplasty – For most patients undergoing knee or hip arthroplasty, we suggest low molecular weight (LMW) heparin or a direct oral anticoagulant (DOAC) as the initial agent in the early perioperative period (Grade 2C). Enoxaparin or dalteparin are LMW heparin agents that are well studied and commonly used. Among the DOACs, we suggest rivaroxaban or apixaban rather than dabigatran or edoxaban (Grade 2C) since there are more data to support their use in this setting. We do not use aspirin as the sole initial agent for VTE prophylaxis in the early postoperative period. Dosing and efficacy of these agents are provided above. (See 'Low molecular weight heparin' above and 'Direct oral anticoagulants' above.)
•Patients undergoing hip fracture surgery – For most patients undergoing hip fracture surgery, we suggest LMW heparin as the preferred agent for the entire duration of prophylaxis (Grade 2C). We generally avoid DOACs in this setting since their safety and efficacy have not been studied in this population. (See 'Low molecular weight heparin' above.)
•Patients with renal failure – Options for patients with severe renal failure (eg, creatinine clearance <30 mL/min or on hemodialysis) include unfractionated heparin (UFH) or warfarin. In most cases, we suggest UFH (Grade 2C). However, warfarin may be used if heparin injections are undesirable. Patients with less severe renal insufficiency can receive LMW heparin with appropriate dose adjustment and monitoring as summarized in the table (table 4). Some DOACs can also be dose-adjusted. (See 'Unfractionated heparin' above and 'Warfarin' above and 'Low molecular weight heparin' above.)
•Patients with heparin-induced thrombocytopenia (HIT) – Patients with HIT or history of HIT should be treated with a nonheparin agent, the details of which are discussed separately. (See "Management of heparin-induced thrombocytopenia".)
●Timing of pharmacologic agents – If LMW heparin is selected for initial pharmacologic prophylaxis, it is typically started preoperatively with an initial dose ≥12 hours before surgery and then continued postoperatively with a second dose ≥12 hours after surgery. Oral agents are generally started 6 to 12 hours or more after surgery, provided that the patient can eat. (See 'Timing of initiation' above.)
●Duration of pharmacologic prophylaxis – For most patients, we suggest that the initial thromboprophylaxis agent be continued for a minimum of 10 to 14 days (algorithm 2) (Grade 2B). Longer or shorter duration may be appropriate depending on the surgery and other risk factors (see 'Duration' above):
•Hip arthroplasty – For patients undergoing total hip arthroplasty, we suggest extending thromboprophylaxis for a total of 35 days (Grade 2B). For most patients, the same agent is used for the entire 35-day course (typically LMW heparin or a DOAC). However, for select lower-risk patients, we suggest transitioning to aspirin after 5 to 10 days of initial therapy with LMW heparin or DOAC and completing the remainder of the 35-day course with aspirin alone (Grade 2B). Lower-risk patients are considered as those who fill all of the following criteria: no other risk factors for VTE, no other indications for long-term anticoagulation, no lower limb or hip fracture in the previous three months, surgery is elective and unilateral, and the patient is ambulatory within 24 hours after surgery. (See 'Duration' above and 'Aspirin' above.)
•Knee arthroplasty – For most patients undergoing total knee arthroplasty who are fully ambulatory and discharged to home within 10 to 14 days, we suggest not extending thromboprophylaxis beyond 14 days (Grade 2C). For lower-risk patients (as defined in the previous bullet), we suggest transitioning to aspirin after five days of initial therapy with LMW heparin or DOAC and completing the remainder of the 10- to 14-day course with aspirin alone (Grade 2B). For other patients, LMW heparin or DOAC prophylaxis is continued for the full 10- to 14-day course. In patients who are not yet ambulatory by 14 days, LMW heparin or DOAC prophylaxis is continued until fully ambulatory or 35 days, whichever is shorter. (See 'Duration' above and 'Aspirin' above.)
•Hip fracture surgery – For patients undergoing hip fracture surgery, we suggest extending thromboprophylaxis for a total of 35 days (Grade 2C). The same agent is used for the entire 35-day course (typically LMW heparin).
●Patients with contraindications to pharmacologic thromboprophylaxis or at high risk of bleeding – For patients with an unacceptably high risk of bleeding from pharmacologic thromboprophylaxis (table 3), we suggest mechanical methods rather than no thromboprophylaxis (Grade 2B). We suggest IPC devices rather than other methods (Grade 2C) since there are more available data on their use in this setting. Vena cava filters should not be routinely used. Mechanical devices are typically placed on the patient just prior to the start of surgery and continued until ambulation, discharge, or transition to pharmacologic thromboprophylaxis. Mechanical methods are less effective than pharmacologic prophylaxis, and it is important to switch to or add a pharmacologic agent as soon as bleeding risk becomes acceptably low. (See 'Patients with unacceptably high bleeding risk' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Menaka Pai, MD, FRCPC, who contributed to earlier versions of this topic review.
