SIGN publication No. The panel judged the costs associated with combined prophylaxis to be moderate based on very low certainty in the evidence about resource requirements. There was possibly important uncertainty or variability about how patients may value these outcomes. The small amount of direct evidence, with a lack of information on undesirable outcomes, together with the very low certainty on the treatment effect, led the panel to consider the indirect data from hip fracture repair studies for treatment RR estimates255-266  and applying baseline VTE and bleeding risks from studies on trauma patients.391,392. Comparison of heparin and foot impulse pump, Prophylaxis of deep venous thrombosis after total hip arthroplasty by using intermittent compression of the plantar venous plexus, A comparison of intermittent calf compression and enoxaparin for thromboprophylaxis in total hip replacement. The panel recognized that this particular comparison applied only to patients undergoing TURP considered at very high risk for VTE (eg, patients with a history of VTE) in whom pharmacological prophylaxis might be considered. The risk of symptomatic proximal DVTs may be reduced (RR, 0.48; 95% CI, 0.25-0.93, very low certainty in the evidence of effects), but we are uncertain of this finding. Our experience in 88 cases [in Italian], Effectiveness and side effects of low-molecular weight heparin-dihydroergotamine in preventing thromboembolism in abdominal surgery [in German], Effect of low molecular weight heparin (Certoparin) versus unfractionated heparin on cancer survival following breast and pelvic cancer surgery: A prospective randomized double-blind trial, Antithrombotic defense during the postoperative period. Likewise, use of LMWH prophylaxis vs UFH prophylaxis appears to result in little or no difference in symptomatic PEs (RR, 0.91; 95% CI, 0.63-1.3; low certainty in the evidence of effects). The guideline panel developed and graded the recommendations and assessed the certainty in the supporting evidence following the GRADE approach.5,6,12-16  The overall guideline-development process, including funding of the work, panel formation, management of conflicts of interest, internal and external review, and organizational approval, was guided by ASH policies and procedures derived from the Guidelines International Network–McMaster Guideline Development Checklist (http://cebgrade.mcmaster.ca/guidecheck.html) and was intended to meet recommendations for trustworthy guidelines by the Institute of Medicine and the Guidelines International Network.1-4. The guideline panel suggests using ASA or anticoagulants for patients undergoing total hip arthroplasty or total knee arthroplasty (conditional recommendation based on very low certainty in the evidence of effects). Distal DVTs may be reduced (RR, 0.52; 95% CI, 0.31-0.87; low certainty in the evidence of effects), but this also corresponds to a negligible effect of 0 fewer symptomatic distal DVT events, irrespective of baseline risk category. This relates to the very low baseline risk of VTE for patients undergoing laparoscopic cholecystectomy. We identified 14 studies139-152  in these reviews that fulfilled our inclusion criteria and measured outcomes relevant to this context. For patients at moderate risk for VTE who are not at high risk for major bleeding complications, it was suggested to use LMWH, low-dose UFH, or mechanical prophylaxis with intermittent pneumatic compression over no prophylaxis. The panel determined that there was possibly important uncertainty or variability in how much affected individuals valued the main outcomes. Five studies reported the effect of pneumatic compression prophylaxis compared with graduated compression stockings prophylaxis on risk of mortality.94,96,97,101,102  Eight studies reported the effect on the development of symptomatic PEs,37,95,96,97,98,99,102,103  and 4 studies reported the effect on any PE.94,100,101,103  One study reported data on symptomatic proximal and symptomatic distal DVTs,98  whereas 6 studies reported on any proximal DVT,37,94,96,98-100  and 5 studies reported on any distal DVT.37,94,96,98,100. For a short explanation of why the committee made the 2020 recommendations and how they might affect practice, see the rationale and impact section on anticoagulation treatment for confirmed DVT or PE . There were no concerns about the feasibility of implementation. The panel judged that this question was only of relevance for patients considered at very high risk for postoperative VTEs following cardiac or major vascular surgery in whom pharmacological prophylaxis would be considered over no prophylaxis. We were unable to assess the effect on reoperations. Considering the very low certainty in the evidence, and possibly important uncertainty about or variability in how much people value the main outcomes, the balance of effects favored LMWH. 17-EHC021-EF, Prevention of venous thromboembolic disease following primary total knee arthroplasty. Supplement 2 provides the complete “Disclosure of Interests” forms of all panel members. They determined that there was very low certainty evidence for any net health benefit/harm from using ASA vs anticoagulants. The guideline panel determined that there was very low certainty evidence for a net health benefit/harm from using LMWH rather than warfarin. It further suggests against placement of an IVC filter for primary VTE prevention, as well as against periodic surveillance with venous compression ultrasound. We rated the overall certainty in the evidence of effects as very low based on the lowest certainty in the evidence for the critical outcomes, downgrading for study limitations and very serious imprecision. Randomised comparison between a low-molecular-weight heparin (nadroparin) and mechanical prophylaxis with a foot-pump system, KANT (Knee Arthroscopy Nadroparin Thromboprophylaxis) Study Group, Low-molecular-weight heparin versus compression stockings for thromboprophylaxis after knee arthroscopy: a randomized trial, Thromboembolic prophylaxis after major abdominal surgery [in Turkish], Thromboembolic prophylaxis for total knee arthroplasty in Asian patients: a randomised controlled trial, Prevention of deep vein thrombosis in urological patients: a controlled, randomized trial of low-dose heparin and external pneumatic compression boots, Thrombosis prevention after total hip arthroplasty: a prospective, randomized trial comparing a mobile compression device with low-molecular-weight heparin, Prevention of postoperative deep venous thrombosis. Based upon available evidence, the panel judged that the incremental desirable and undesirable effects of pharmacological prophylaxis were trivial and, therefore, balanced. Once again, we are very uncertain about this finding. The panel did not consider potential harms of IVC filters beyond VTE. We identified 1 systematic review that addressed this question.389  Our update of the systematic review identified 1 additional study that fulfilled the inclusion criteria,394  and our systematic search of RCTs identified 2 studies that fulfilled the inclusion criteria394,395  and were not included in the review. and P.D. Remark: Patients with other risk factors for VTE (such as history of VTE, thrombophilia, or malignancy) may benefit from pharmacological prophylaxis. For patients experiencing major trauma in whom pharmacological prophylaxis is used, the ASH guideline panel suggests using LMWH or UFH (conditional recommendation based on low certainty in the evidence of effects ⊕⊕◯◯). Sixteen studies122,125,274-278,284,285,291,293,296,297,299,300,302  reported the effect of pharmacological prophylaxis vs no pharmacological prophylaxis on the risk of mortality, and 11 studies125,273,276-279,285,286,289,293,295  reported the effect on the development of symptomatic PEs. https://guidelines.gradepro.org/profile/434A9C2D-3417-F3ED-B7C1-4A0BA3EC6699. Mechanical methods of perioperative VTE prophylaxis have been addressed by a number of guidelines.398,400-404  The 2012 ACCP guidelines did not provide a detailed comparison of the effectiveness of graduated compression stockings and pneumatic compression stockings, but they generally favor pneumatic compression stockings on the basis of indirect evidence, from the Clots in Legs or Stockings after Stroke trial for patients with stroke, that elastic stockings increased the risk of skin complications without reducing the risk of VTEs.405  Other guidelines presented by SIGN,400  NICE,401  the American Academy of Orthopedic Surgeons (AAOS),402  the Neurocritical Society,404  and the International Union of Angiology403  discuss the use of pneumatic compression and graduated compression stockings in various surgical settings but generally consider these modalities together as “mechanical devices” and do not offer a direct comparison of their effectiveness or safety other than noting that graduated compression stockings cannot be used for patients with certain lower extremity pathologies. The panel recommended a need for large clinical trials using clinically relevant end points comparing different DOACs. Available at: Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery, Prolonged versus standard-duration venous thromboprophylaxis in major orthopedic surgery: a systematic review, Extended thromboprophylaxis with low-molecular-weight heparins after hospital discharge in high-risk surgical and medical patients: a review, Low molecular weight heparin versus other anti-thrombotic agents for prevention of venous thromboembolic events after total hip or total knee replacement surgery: a systematic review and meta-analysis, The effectiveness of graduated compression stockings for prevention of venous thromboembolism in orthopedic and abdominal surgery patients requiring extended pharmacologic thromboprophylaxis, Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomised trials, Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review, Reduction of out-of-hospital symptomatic venous thromboembolism by extended thromboprophylaxis with low-molecular-weight heparin following elective hip arthroplasty: a systematic review, Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement, North American Fragmin Trial Investigators, Low-molecular-weight heparin prophylaxis using dalteparin extended out-of-hospital vs in-hospital warfarin/out-of-hospital placebo in hip arthroplasty patients: a double-blind, randomized comparison, Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty--the Danish Prolonged Prophylaxis (DaPP) Study, Prolonged prophylaxis with unfractioned heparin is effective to reduce delayed deep vein thrombosis in total hip replacement, Prolonged thromboprophylaxis with oral anticoagulants after total hip arthroplasty: a prospective controlled randomized study, Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer, Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study, PENTasaccharide in HIp-FRActure Surgery Plus Investigators, Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery: a multicenter, randomized, placebo-controlled, double-blind study, Postoperative activation of the haemostatic system--influence of prolonged thromboprophylaxis in patients undergoing total hip arthroplasty, The post-discharge prophylactic management of the orthopedic patient with low-molecular-weight heparin: enoxaparin, Prolonged thromboprophylaxis following hip replacement surgery--results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin (Fragmin), Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo, Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement, Incidence and prevention of deep venous thrombosis occurring late after general surgery: randomised controlled study of prolonged thromboprophylaxis, Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial, The use of extended perioperative low molecular weight heparin (tinzaparin) to improve disease-free survival following surgical resection of colon cancer: a pilot randomized controlled trial, Reduction of venous thromboembolism following prolonged prophylaxis with the low molecular weight heparin certoparin after endoprothetic joint replacement or osteosynthesis of the lower limb in elderly patients, Extended prophylaxis with bemiparin for the prevention of venous thromboembolism after abdominal or pelvic surgery for cancer: the CANBESURE randomized study, A randomized study on 1-week versus 4-week prophylaxis for venous thromboembolism after laparoscopic surgery for colorectal cancer, Efficacy and safety of rivaroxaban in preventing deep venous thromboembolism after major orthopedic operations, Steering Committee of the Pentasaccharide in Major Knee Surgery Study, Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery, Flexibility in administration of fondaparinux for prevention of symptomatic venous thromboembolism in orthopaedic surgery, PENTATHALON 2000 Study Steering Committee, Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial [published correction appears in, BAY 59-7939: an oral, direct factor Xa inhibitor for the prevention of venous thromboembolism in patients after total knee replacement. Effectiveness and tolerance of low molecular weight heparin in combination with dihydroergotamine, Role of low molecular weight heparin in the prevention of postoperative deep venous thrombosis. For the subset of patients undergoing major neurosurgical procedures for whom pharmacological prophylaxis is used, the ASH guideline panel suggests using LMWH over UFH (conditional recommendation based on very low certainty in the evidence of effects ⊕◯◯◯). This would correspond to 4 fewer deaths (11 fewer to 5 more) per 1000 patients based on a baseline risk of 7.1% from the control group event rate in the meta-analysis. Implementation of the guidelines will be facilitated by the related interactive forthcoming decision aids. Question: Should combined pharmacological and mechanical prophylaxis vs pharmacological prophylaxis alone be used for patients undergoing major surgery? Decision aids may be useful in helping individuals to make decisions consistent with their individual risks, values, and preferences. Question: Should pharmacological prophylaxis vs no pharmacological prophylaxis be used for patients undergoing major gynecological surgery? Because of the paucity of studies related to TURP, data across all major general, urological, and gynecological surgical procedures were pooled, and TURP-specific baseline risk estimates were applied, where available. For patients undergoing radical prostatectomy in whom pharmacological prophylaxis is used, the ASH guideline panel suggests using LMWH or UFH (conditional recommendation based on very low certainty in the evidence of effects ⊕◯◯◯). Pharmacological prophylaxis may result in more major bleeding than no prophylaxis (RR, 1.24; 95% CI, 1.12-1.37; very low certainty in the evidence of effects), but this finding is uncertain. Of the 7 studies included in the analysis, 2 studies compared ASA with UFH,193,195  4 studies compared ASA with LMWH,194,196,198,199  and 2 studies compared ASA with oral anticoagulants.197,199  All 7 studies reported the outcomes of mortality and PE,193-199  6 studies reported on proximal and distal DVTs,195-199  and 5 studies reported on major bleeding.194-196,198,199  We found no studies addressing the outcome of reoperation. Based primarily on the very low baseline risk of VTE following TURP, the panel judged that the balance of effects ultimately favored not using pharmacological prophylaxis. Thirty-one49,122,125,131,275-279,281-293,295-300,302  studies were conducted on patients undergoing major general surgery. We rated the overall certainty in the evidence of effects as low based on the lowest certainty in the evidence for the critical outcomes, downgrading twice for very serious imprecision. We rated the overall certainty in the evidence of effects as moderate based on the lowest certainty in the evidence for the critical outcomes, downgrading for imprecision. A compararative study of calcium heparinate and sodium pentosan polysulfate, Intraoperative single-dose heparin prophylaxis against deep-vein thrombosis, Efficacy of low doses of heparin in prevention of deep-vein thrombosis after major surgery. Question: If pharmacological prophylaxis is indicated, should LMWH vs UFH be used for patients undergoing radical prostatectomy? For patients undergoing laparoscopic cholecystectomy, the ASH guideline panel suggests against using pharmacological prophylaxis (conditional recommendation based on very low certainty in the evidence of effects ⊕◯◯◯). Is the 2 hour daily minimum application sufficient? The panel did not believe that there were important implementation considerations with use of postoperative LMWH or UFH pharmacological prophylaxis in this patient population. This would correspond to 8 more (17 fewer to 122 more) symptomatic proximal DVTs per 1000 patients and 0 more (1 fewer to 4 more) symptomatic distal DVTs per 1000 patients based on baseline risks of 2.4% and 0.2%, respectively. For patients deemed at high risk for major bleeding (because of the nature of the surgical procedure), there is likely a net benefit in favor of mechanical prophylaxis. For policy makers: policy-making will require substantial debate and involvement of various stakeholders. We identified 1 systematic review254  that addressed this question. Extended antithrombotic prophylaxis vs short-term antithrombotic prophylaxis, 8. The panel followed best practice for guideline development recommended by the Institute of Medicine (now the National Academy of Medicine) and the Guidelines International Network.1-4  The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach5,6  to assess the certainty in the evidence and formulate recommendations. The trials were reviewed by the panel but were not included in the main meta-analysis because of differences in the comparator groups. Conflict-of-interest disclosure: All authors were members of the guideline panel or of the systematic review team. Costs and saving would likely be negligible, and the panel saw no particular issues related to equity, acceptability, or feasibility. Cost-effectiveness likely differs by country but probably favors LMWH. Sixteen individuals or organizations submitted comments. A randomized prospective study, Prospective double-arm study of fibrinolysis in surgical patients, Venous thromboembolism prophylaxis after head and spinal trauma: intermittent pneumatic compression devices versus low molecular weight heparin, Prevention of deep venous thrombosis in spinal surgery: comparison of intermittent sequential pneumatic compression versus low molecular weight heparin, Prevention of venous thromboembolism after total knee replacement by high-dose aspirin or intermittent calf and thigh compression, Prophylaxis of deep vein thrombosis after major abdominal surgery. Based upon the very low baseline risk for patients undergoing TURP, this would correspond to 0 fewer symptomatic events per 1000 higher-risk patients. These guidelines focus on the optimal management of anticoagulant drugs for the prevention and treatment of VTE following the choice of an anticoagulant. 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