1 Venous Thromboembolism Prophylaxis – Adult – Inpatient/Ambulatory Consensus Care Guideline Table of Contents INTRODUCTION: .................................................................................................................................. 3 DEFINITIONS ........................................................................................................................................ 3 RECOMMENDATIONS: ......................................................................................................................... 3 METHODOLOGY ................................................................................................................................. 12 COLLATERAL TOOLS & RESOURCES: .................................................................................................... 13 APPENDIX A. VTE PROPHYLAXIS IN MEDICAL PATIENTS ..................................................................... 14 APPENDIX B. VTE PROPHYLAXIS IN SURGICAL PATIENTS .................................................................... 15 APPENDIX C. VTE PROPHYLAXIS IN ORTHOPEDIC SURGERY ................................................................ 17 Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 2 Content Expert(s): Name: Anne Rose, PharmD - Pharmacy Email Address: arose@uwhealth.org Contact for Changes: Name: Anne Rose, PharmD - Pharmacy Email Address: arose@uwhealth.org Guideline Author(s): Anne Rose, PharmD – Pharmacy Workgroup Members: Carlie Wilke, PharmD – Pharmacy East Madison Hospital Reviewer(s): Ann O’Rourke, MD – Surgery/Trauma Inpatient Anticoagulation Committee Committee Approval(s): Inpatient Anticoagulation Committee: • Initial review: April 2010 • Last periodic review: March 2023 Pharmacy & Therapeutics Committee • Initial review: April 2010 • Last periodic review: March 2023 Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 3 Introduction: Hospital admission for surgical interventions or acute medical illness accounts for nearly 50% of all venous thromboembolism (VTE) events.1,2 Hospital acquired VTE has been considered the most common cause of preventable death. Both patient specific risk factors and procedural risk factors should be considered to determine who is at high risk for VTE.2,3 There have been many risk factors identified in both the medical and surgical patient populations that can increase the risk of developing VTE. This guideline provides recommendations on the use of risk assessment models (RAM), validated in their respective patient populations, with the intent to identify patients who are at high risk for VTE and to provide recommendations for appropriate VTE prophylaxis modalities. Definitions 1. Obesity Class 3 – patients with a BMI > 40 (kg/M2) 4,5 2. Renal failure – patients with a CrCl< 30 mL/min or evidence of stage 4 [eGFR 15-29 mL/min/1.73M2] or 5 [eGFR < 15 mL/min/M2] renal dysfunction 3. Mechanical prophylaxis – methods may include graduated compression stockings (GCS), intermittent pneumatic compression devices (IPC), and venous foot pumps (VFP)3 Recommendations: 1. Considerations for Hospitalized Patients3,6 1.1. All hospitalized patients should be evaluated for both bleeding and VTE risk within 24 hours of admission, upon transferring level of care, and periodically during the hospital stay. (UW Health GRADE Moderate quality evidence, strong recommendation) 1.2 Documentation of initial bleeding and VTE risk should occur in the medical record within 24 hours of hospital admission or postsurgical procedure. (UW Health GRADE Very low quality evidence, strong recommendation) 1.3 Reassessment of bleeding and VTE risk should occur in the medical record when there is a change in medical condition or level or care. (UW Health GRADE Very low quality evidence, strong recommendation) 2. Evaluation of Bleeding Risk There is no universally validated model to assess the potential for bleeding from receiving prophylactic anticoagulation in surgical patients.3 The IMPROVE investigators did create an externally validated RAM for bleeding in medical patients.7,8 This is described in Table 1. Additional general considerations for both surgical and medical patients are listed in Table 2. Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 4 Table 1. IMPROVE bleeding RAM for medical patients7,8 Renal dysfunction (GFR 30-59 mL/min) 1 Male 1 Age 40-84 years old 1.5 Current cancer 2 Rheumatic disease 2 Central venous catheter 2 ICU/Critical care unit during admission 2.5 Renal failure (GFR < 30 mL/min) 2.5 Hepatic failure (INR > 1.5) 2.5 Age >84 years old 3.5 Platelet count < 50 x109/L 4 Bleeding in the 3 months prior to admission 4 Active gastroduodenal ulcer 4 • A score of < 7: 0.4%-1.5% risk for bleeding • A score of > 7: 4.1%-7.9% risk for bleeding Table 2. Bleeding risk factor consideration for medical and surgical patients2,3 Medical Patients* Surgical Patients Platelet count < 50 x109/L Active bleeding or previous major bleeding Bleeding in the 3 months prior to admission Renal failure (CrCl < 30 mL/min) Active gastroduodenal ulcer Hepatic failure (INR > 1.5 without anticoagulants) Thrombocytopenia Acute stroke Uncontrolled systemic hypertension Concomitant use of anticoagulants, antiplatelets or thrombolytics • *Risk factors listed under medical patients are considered absolute contraindications to anticoagulation while risk factors listed under surgical patients are relative contraindications 3. Evaluating VTE risk in medical patients 3.1 UW Health endorses the use of the Padua RAM and modified this to incorporate additional VTE risk factors. This RAM was selected based on support in the literature and ease of use for medical patients.1,3,9 (UW Health GRADE Moderate quality evidence, strong recommendation) See Table 3. Table 3: Modified Padua Risk Assessment Model1,3,10,11 Risk Factor Points Critically Ill 4 Inflammatory Bowel Disease 4 Admission for trauma (injured patient with fracture) 4 Active COVID-19 infection 4 Active Cancer 3 Previous VTE 3 Reduced Mobility 3 Thrombophilic Condition 3 Recent (< 1month) Trauma/Surgery 2 Age ≥ 70 years 1 Heart or Respiratory Failure 1 Acute Myocardial Infarction or Ischemic Stroke 1 Acute Infection or Rheumatologic Disorder 1 BMI ≥ 30 1 Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 5 Ongoing Hormonal Treatment 1 Total Points Low VTE Risk – no prophylaxis needed < 4 High VTE Risk – prophylaxis recommended > 4 • Critically ill is defined as a patient being followed by a critical care service, admitted under an ICU status, or has been admitted for stroke • Inflammatory bowel disease is limited to Crohn’s disease and ulcerative colitis. • Active cancer is defined as local or distant metastases and with chemotherapy or radiation in the previous 6 months • Reduced mobility is defined as anticipated bed rest with bathroom privileges for at least 3 days, if immobile at baseline, or admitted from an outside facility where they were immobile > 72 hours • Thrombophilic condition is defined as defects of antithrombin, protein C or S, factor V Leiden, G20210A prothrombin mutation, active heparin induced thrombocytopenia or antiphospholipid syndrome • Heart or respiratory failure implies an admission for heart failure exacerbation, asthma or COPD exacerbation, cystic fibrosis exacerbation or admitted for continuous BiPAP. • Rheumatologic disorder examples: rheumatoid arthritis, Lupus, Sjögren’s Syndrome • Ongoing hormonal treatment includes: oral contraceptives, estrogen replacement or testosterone injections 3.2 Medical patients identified as high VTE risk should receive the corresponding prophylaxis based on individual considerations. See recommendations in Table 4. (UW Health GRADE Low quality evidence, strong recommendation) 3.2.1 Enoxaparin is the preferred pharmacologic prophylaxis agent for medical patients.3 (UW Health GRADE Moderate quality evidence, strong recommendation) 3.2.2 If UFH is heparin is used, every 12 hours dosing regimen is preferred.12,13 (UW Health GRADE Moderate quality evidence, strong recommendation) 3.2.3 When utilizing mechanical prophylaxis IPC devices are preferred14-16 (UW Health GRADE Moderate quality evidence, strong recommendation) Table 4: VTE Prophylaxis Regimens for High VTE Risk Medical Patients3,12,13,17-21 Patient Population VTE Prophylaxis Regimens Preferred Option Alternative Option High VTE Risk Enoxaparin 40 mg SQ every 24 hrsa Heparin 5000 units SQ every 8-12 hrsa Trauma/Injury with fracture Enoxaparin 30 mg SQ every 12 hrsa Enoxaparin 0.5 mg/kg every 12 hrs Heparin 5000 units SQ every 8-12 hrsc Renal failure (CrCl < 30 mL/min)* *Not on renal replacement therapy Heparin 5000 units SQ every 8-12 hrsa Enoxaparin 30 mg SQ every 24 hrsb Obesity Class 3 (BMI > 40 kg/M2) Enoxaparin 40 mg SQ every 12 hrsb Heparin 5000 units SQ every 8 hrsb Low body weight (weight < 50 kg) Heparin 5000 units SQ every 8-12 hrsa Enoxaparin 30 mg SQ every 24 hrsc High Bleeding Risk Intermittent pneumatic compression devices (IPC)a Graduated compression stockings (GCS) or Venous foot pumps (VFP)c a: UW Health GRADE Moderate quality evidence, strong recommendation b: UW Health GRADE Low quality evidence, strong recommendation Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 6 c: UW Health GRADE Low quality evidence, weak/conditional recommendation 3.3 Refusal of parenteral prophylaxis during hospital admission22-25 Oral anti-Xa inhibitors have been studied for extended VTE prevention versus enoxaparin. While similar outcomes in VTE prevention were seen when compared to enoxaparin, higher major bleeding was also seen with these agents. 3.3.1 Oral anticoagulants may be considered in high VTE risk medical patients who refuse parenteral VTE prophylaxis.22-25 (UW Health GRADE Low quality evidence, weak/conditional recommendation) 3.3.2 Apixaban 2.5 mg by mouth twice daily22 (UW Health GRADE Moderate quality evidence, weak/conditional recommendation) 3.3.3 Rivaroxaban 10 mg by mouth daily23,25 (UW Health GRADE Moderate quality evidence, weak/conditional recommendation) 3.3.4 Avoid use in patients with CrCl < 30 mL/min 4. Evaluating VTE risk in surgical patients 4.1 UW Health endorses the use of the Caprini RAM. This RAM was selected based on support in the literature for general surgery patients. It should be used to assess VTE risk in general and abdominal-pelvic surgery patients.6,26 See Table 5. (UW Health GRADE Moderate quality evidence, strong recommendation) Table 5: Caprini Risk Assessment Model2,26 (UW Health GRADE Moderate quality evidence, strong recommendation) 1 Point 2 Points 3 Points 5 Points Age 41-60 Age 61-74 Age ≥ 75 Acute spinal cord injury (< 1 mo) Acute MI (<1 mo) Central venous access Established thrombophilia Elective lower extremity arthroplasty BMI > 25 Immobile > 72 hrs HIT Hip, pelvis, or leg fracture (< 1 mo) CHF exacerbation (<1 mo) Leg plaster cast or brace Hx of VTE Stroke (< 1 mo) Hx of Inflammatory Bowel Disease Malignancy Family hx VTE (1 degree relative) Procedure with local anesthesia Surgery- arthroscopic Swollen legs or Varicose veins Surgery > 45 mins Sepsis (< 1 mo) Serious lung dx ex. Pneumonia (<1 mo) 1 point (For Women Only) Oral contraceptives or HRT Pregnancy or postpartum (< 1 month) Hx of unexplained stillborn infant, spontaneous abortion (≥3), premature birth with toxemia or growth restricted infant Points Risk Recommendation 0 Very Low VTE Risk Early and frequent ambulation 1-2 Low VTE Risk Mechanical Prophylaxis 3-4 Moderate VTE Risk and Low Bleed Risk Pharmacologic Prophylaxis Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 7 > 5 High VTE Risk and Low Bleed Risk Mechanical AND Pharmacologic Prophylaxis > 2 High Bleed Risk Mechanical Prophylaxis • Established thrombophilia is defined as factor V Leiden, G20210A prothrombin mutation, antiphospholipid syndrome, and lupus anticoagulant.2,26 (UW Health GRADE Moderate quality evidence, strong recommendation) • Inflammatory bowel disease is limited to Crohn’s disease and ulcerative colitis. • Malignancy is defined as local or distant metastases and with chemotherapy or radiation in the previous 6 months 4.3 Surgical patients not included in the Caprini RAM who classify as high VTE risk should receive the corresponding prophylaxis based on individual considerations. See recommendations in Table 6. (UW Health GRADE Low quality evidence, strong recommendation) Table 6: VTE Prophylaxis Regimens for High VTE Risk General Surgery Patients2,12,13,15,16,20,27-34 Patient Population VTE Prophylaxis Regimens Preferred Option Alternative Option High VTE Risk Heparin 5000 units SQ every 8-12 hrsa Enoxaparin 40 mg SQ every 24 hrsa Renal impairment (CrCl < 30 mL/min)* *Not on hemodialysis Heparin 5000 units SQ every 8-12 hrsa Enoxaparin 30 mg SQ every 24 hrsb Bariatric Surgery Enoxaparin 40 mg SQ every 12 hrsa Heparin 5000 units SQ every 8-12 hrsc Major Trauma Enoxaparin 30 mg SQ every 12 hrsa Enoxaparin 0.5 mg/kg every 12 hrs Heparin 5000 units SQ every 8-12 hrsc Abdominal/Pelvic Surgery for Cancer Enoxaparin 40 mg SQ every 24 hrsb Heparin 5000 units SQ every 8-12 hrsc High Bleed Risk Intermittent pneumatic compression devices (IPC)a Graduated compression stockings (GCS) or Venous foot pumps (VFP)c Cardiac Surgery Heparin 5000 units SQ every 8-12 hrs Enoxaparin 40 mg SQ every 24 hrs Craniotomy Intermittent pneumatic compression devices (IPC)a Graduated compression stockings (GCS) or Venous foot pumps (VFP)c Spinal Surgery Intermittent pneumatic compression devices (IPC)a Graduated compression stockings (GCS) or Venous foot pumps (VFP)c Thoracic Surgery Heparin 5000 units SQ every 8-12 hrs Enoxaparin 40 mg SQ every 24 hrs Trauma Surgery Enoxaparin 30 mg every 12 hrsa Enoxaparin 0.5 mg/kg every 12 hrs Heparin 5000 units SQ every 8-12 hrsc a: UW Health GRADE Moderate quality evidence, strong recommendation b: UW Health GRADE Low quality evidence, strong recommendation c: UW Health GRADE Low quality evidence, weak/conditional recommendation 4.4 Orthopedic Surgery35-43 There is no validated VTE RAM for orthopedic patients. Generally, patients undergoing orthopedic surgery are considered at risk for VTE. Determining if a surgical orthopedic patient is at a standard or elevated VTE risk is based on the additional risk factors present. While most patients will receive pharmacologic prophylaxis for VTE, it is the Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 8 level of VTE risk balanced with the bleed risk that dictates the selected regimen.35-43 Table 7 outlines considerations for elevated VTE risk based on specific risk factors. Recommendations for VTE prevention strategies for patients undergoing elective hip or knee arthroplasty or hip fracture surgery based on VTE and bleeding risks are listed in Table 8. Selections are listed alphabetically. Table 7. VTE Risk Categories for Orthopedic Surgery Population 35-43 (UW Health GRADE moderate quality of evidence, weak/conditional recommendation) Elevated Risk (if any are present) Elevated Risk (if 2 or more are present) Hip fracture surgery Age > 70 years Surgical revision or protective weight bearing New onset ischemic stroke Personal history of DVT or PE Morbid obesity (BMI > 40 or >120 kg) History of active malignancy Venous stasis (varicose veins) History of known thrombophilia Active heart failure (NYHA Class III or IV) Acute myocardial infarction Acute respiratory disease (COPD or asthma exacerbation or pneumonia) 1st degree family history of DVT or PE Active (treated) inflammatory disease (IBD, rheumatic disease Immobility (bedridden > 72 hrs, immobilizing lower extremity cast, paralysis) • Active malignancy is defined as local or distant metastases and/or in whom chemotherapy or radiotherapy had been performed in the last 6 months • Known thrombophilia is defined as factor V Leiden, prothrombin gene mutation, antiphospholipid antibody syndrome, lupus anticoagulant, anticardiolipin antibodies, antithrombin deficiency, protein C deficiency, protein S deficiency, sickle cell anemia, myeloproliferative disorder, JAK-2 mutation Table 8. VTE prophylaxis regimens for orthopedic surgeries35-43 Standard VTE Risk Elevated VTE Risk High Bleed Risk Total Hip, Total Knee, or Shoulder Arthroplasty Apixaban 2.5 mg PO BIDa ASA 81 mg BID b ASA 325 mg QD - BID b Enoxaparin 40 mg SQ dailya Enoxaparin 30 mg SQ every 12 hrsa *Fondaparinux 2.5 mg daily b Rivaroxaban 10 mg PO dailya Warfarin (target INR 1.8-2.2) b Apixaban 2.5 mg PO BIDa Enoxaparin 30 mg SQ every 12 hrsa Enoxaparin 40 mg SQ dailya *Fondaparinux 2.5 mg daily b Rivaroxaban 10 mg PO dailya Warfarin (target INR 1.8-2.2) b Mechanical prophylaxis Hip Fracture Surgery All patients considered at elevated VTE risk: Apixaban 2.5 mg BID Enoxaparin 30 mg SQ every 12 hrsa Enoxaparin 40 mg Sq every 24 hrsa *Fondaparinux 2.5 mg daily b Rivaroxaban 10 mg PO dailya Warfarin (target INR 1.8-2.2) b Mechanical prophylaxis * May be considered for patients with heparin allergy a: UW Health GRADE Moderate quality evidence, strong recommendation b: UW Health GRADE Very Low quality evidence, strong recommendation Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 9 4.4.1 Patients receiving therapeutic anticoagulation prior to procedure should resume therapeutic anticoagulation therapy post procedure. (UW Health GRADE Moderate quality evidence, strong recommendation) 5. VTE Prophylaxis for Special Populations 5.1 Acute kidney injury (AKI) or chronic kidney disease (CKD) 5.1.1 UFH is the preferred agent for patients who are on renal replacement therapy44 (UW Health GRADE Low quality evidence, strong recommendation) 5.1.2 Enoxaparin 30 mg every 24 hours may be considered18,19,21,44 (UW Health GRADE Low quality evidence, weak/conditional recommendation) 5.1.2.1 Consider monitoring anti-Xa level after 7-10 doses to evaluate for accumulation (UW Health GRADE Low quality evidence, weak/conditional recommendation) 5.1.2.2 Goal anti-Xa 0.2-0.4 units/mL 5.2 Obesity17,19,21,44-47 5.2.1 Optimal thromboprophylaxis has not been established (UW Health GRADE Low quality evidence, weak/conditional recommendation) 5.2.2 Enoxaparin 40 mg every 12 hours is the preferred agent for VTE prevention in obese patients (UW Health GRADE Moderate quality evidence, strong recommendation) 5.2.2.1 Routine anti-Xa monitoring is not recommended (UW Health GRADE Very low quality evidence, weak/conditional recommendation) 5.2.3 Prophylactic UFH has not been adequately studied in morbidly obese patients (UW Health GRADE Low quality evidence, weak/conditional recommendation) 5.2.3.1 May consider heparin 5000 - 7,500 units every 8 hours45-47 (UW Health GRADE Low quality evidence, weak/conditional recommendation) 5.3 History of Heparin Induced Thrombocytopenia 5.3.1 Unfractionated and low molecular weight heparins are not recommended.48 (UW Health GRADE High quality evidence, strong recommendation) 5.3.2 Fondaparinux 2.5 mg SQ every 24 hours42 (UW Health GRADE Low quality evidence, strong recommendation) 5.3.3 Apixaban 2.5 mg BID for 30 days or rivaroxaban 10 mg daily (UW Health GRADE Low quality evidence, weak/conditional recommendation) 18-21 6. Extended duration VTE prophylaxis upon hospital discharge. 6.1 Bariatric surgery15,49 6.1.1 Recommended for patients with high VTE risk, low bleed risk and BMI > 55 kg/m2 (UW Health GRADE Moderate quality evidence, strong recommendation) 6.1.2 Enoxaparin 40 mg SQ every 12 hours for 10 days (UW Health GRADE Moderate quality evidence, strong recommendation) 6.2 Abdominal or pelvic surgery for cancer49,50 6.2.1 Recommended for patients with a cancer diagnosis who received a traditional laparotomy or vulvectomy and is either > 60 years or < 60 years old with a history of VTE (UW Health GRADE Low quality evidence, strong recommendation) 6.2.2 Enoxaparin 40 mg SQ every 24 hours for 28 days (UW Health GRADE Moderate quality evidence, strong recommendation) Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 10 6.2.3 If patient refuses 28 days of prophylactic therapy then enoxaparin or UFH may be considered for 14 days (UW Health GRADE Low quality evidence, strong recommendation) 6.3 Orthopedic surgery43,51 6.3.2 Total hip or knee arthroplasty: 10-14 days (UW Health GRADE Moderate quality evidence, strong recommendation) 6.3.3 Hip fracture surgery: 4 – 6 weeks (UW Health GRADE Moderate quality evidence, strong recommendation) 6.3.4 For major orthopedic surgery extended prophylaxis up to 35 days may be considered. (UW Health GRADE Low quality evidence, strong recommendation) 6.4 Medical patients:22-25 The oral Xa inhibitors have been compared to enoxaparin for prevention of VTE after hospital discharge. In these extended VTE prophylaxis studies the oral Xa inhibitors did not provide additional benefit in preventing VTE 30-45 days post discharge but were associated with an increased risk in major bleeding. Extended VTE prophylaxis for medical patients is not a standard of care for most patients. Identifying the highest risk patients who may benefit from extended prophylaxis has yet to be determined. 6.4.1 Apixaban 2.5 mg BID for 30 days or rivaroxaban 10 mg daily for 45 days may be considered for high risk medical patients to prevent VTE post discharge. (UW Health GRADE Low quality evidence, weak/conditional recommendation) 6.5 COVID-19 Hospitalization52-54 6.5.1 Extended VTE prophylaxis is not necessary for all patients with COVID-19 who are being discharged after acute hospital admission. (UW Health GRADE Low quality evidence, weak/conditional recommendation 6.5.2 Extended VTE prophylaxis may be considered for patients with an IMPROVED-D VTE score of 4 or more (see Table 9). The primary team should determine ongoing VTE risk factors and if the patient may benefit from extended post-hospital VTE prophylaxis. (UW Health GRADE Low quality evidence, weak/conditional recommendation 6.5.3 If extended VTE prophylaxis is deemed reasonable, recommend use of adequately studied and/or approved agent and suggest limiting the total duration as used in the clinic trials (i.e., enoxaparin 40 mg daily for 6-14 days; rivaroxaban 10 mg daily for 31-39 days) adjusted as needed based on weight, renal/liver function and drug-drug interactions. (UW Health GRADE Low quality evidence, strong recommendation Table 9. IMPROVED-D VTE RAM for Extended VTE Prophylaxis Risk Factor Score History of VTE 3 Thrombophilia 2 Paralysis of lower extremity during hospitalization 2 Current malignancy 2 D-dimer > 2x ULN 2 Immobilization for at least 7 days 1 ICU or CCU during hospitalization 1 Age > 60 years 1 Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 11 7. Anticoagulant Monitoring44 7.1 Platelets (PLT) 7.1.1 Baseline PLT should be obtained within 48 hours of starting heparin or enoxaparin (UW Health GRADE very low quality evidence, strong recommendation) 7.1.2 Recheck PLT 24 hours after initiating heparin or enoxaparin therapy and every other day thereafter for up to 14 days or until therapy is discontinued (UW Health GRADE very low quality evidence, strong recommendation) 7.1.3 If PLT count decreases > 50% from baseline or if PLT count falls below 100 x 109/L; See Heparin Induced Thrombocytopenia – Adult- CPG (UW Health GRADE very low quality evidence, strong recommendation) 7.2 Hemoglobin/Hematocrit (Hgb/HCT) 7.2.1 Obtain a baseline Hgb or HCT prior to initiating anticoagulant therapy (UW Health GRADE very low quality evidence, strong recommendation) 7.2.2 Recheck Hgb/HCT a minimum of every 3 days thereafter (UW Health GRADE very low quality evidence, strong recommendation) 7.3 After hospital discharge PLT and CBC should be monitored only as clinically indicated (UW Health GRADE very low quality evidence, strong recommendation) Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 12 Disclaimer Consensus care models assist clinicians by providing a framework for the evaluation and treatment of patients. This guideline outlines the preferred approach for most patients. It is not intended to replace a clinician’s judgment or to establish a protocol for all patients. It is understood that some patients will not fit the clinical condition contemplated by a guideline and that a guideline will rarely establish the only appropriate approach to a problem. Conflicts of Interest All guideline workgroup members are expected to follow institutional policies and procedures around conflicts of interest. Actions in which a guideline member discloses a conflict of interest relevant to the guideline topic may include, but is not limited to, abstaining from voting, dismissal during comment and voting period, or recusal from requesting and/or participation in the decision-making process. Methodology Development Process Each guideline is reviewed and updated approximately every 3 years, in consideration of the primary literature and relevant practice changes. All guidelines are developed using the guiding principles, standard processes, and styling outlined in the UW Health Clinical Practice Guideline Resource Guide. This includes expectations for workgroup composition and recruitment strategies, disclosure and management of conflict of interest for participating workgroup members, literature review techniques, evidence grading resources, required approval bodies, and suggestions for communication and implementation. GRADE Methodology adapted by UW Health Rating Scheme for the Strength of the Evidence/Recommendations: Table 1. GRADE Ranking of Evidence High We are confident that the effect in the study reflects the actual effect. Moderate We are quite confident that the effect in the study is close to the true effect, but it is also possible it is substantially different. Low The true effect may differ significantly from the estimate. Very Low The true effect is likely to be substantially different from the estimated effect. Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 13 Table 2. GRADE Ratings for Recommendations for or Against Practice Strong (S) Generally, should be performed (i.e., the net benefit of the treatment is clear, patient values and circumstances are unlikely to affect the decision.) Conditional (C) May be reasonable to perform (i.e., may be conditional upon patient values and preferences, the resources available, or the setting in which the intervention will be implemented.) Revise guideline as necessary, based on workgroup feedback and continued evidence Collateral Tools & Resources: The following collateral tools and resources support staff execution and performance of the evidence-based guideline recommendations in everyday clinical practice. Metrics 1. Performance Measure VTE CMS 108: VTE prophylaxis received within 24 hours of admission or documented reason why none received 2. Performance Measure VTE CMS 190: VTE prophylaxis received within 24 hours of admission or documented reason why none received for ICU patients 3. Patient Safety Indicator 12: Post-operative VTE events 4. Hospital acquired VTE events Best Practice Alerts (BPA) 1. VTE risk assessment BPA for pharmacists Order Sets & Smart Sets Included in all admission, transfer, and postoperative order sets Patient Resources 1. Health Facts For You #7522 – Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) Treatment and Prevention 2. Health Facts For You #6915 – Heparin (Unfractionated and Low Molecular Weight Heparin) 3. Health Facts For You #6900 – Warfarin (Coumadin®, Jantoven®) Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 14 Venous Thromboembolism Prophylaxis – Adult – Inpatient/Ambulatory Appendix A. VTE Prophylaxis in Medical Patients Modified Padua Risk Assessment Model1,3,10,11 Risk Factor Points Critically Ill 4 Inflammatory Bowel Disease 4 Admission for trauma (injured patient with fracture) 4 Active COVID-19 infection 4 Active Cancer 3 Previous VTE 3 Reduced Mobility 3 Thrombophilic Condition 3 Recent (< 1month) Trauma/Surgery 2 Age ≥ 70 years 1 Heart or Respiratory Failure 1 Acute Myocardial Infarction or Ischemic Stroke 1 Acute Infection or Rheumatologic Disorder 1 BMI ≥ 30 1 Ongoing Hormonal Treatment 1 Total Points Low VTE Risk – no prophylaxis needed < 4 High VTE Risk – prophylaxis recommended > 4 VTE Prophylaxis Regimens for High VTE Risk Medical Patients3,12,13,17-21 Patient Population VTE Prophylaxis Regimens Preferred Option Alternative Option High VTE Risk Enoxaparin 40 mg SQ every 24 hrsa Heparin 5000 units SQ every 8-12 hrsa Trauma/Injury with fracture Enoxaparin 30 mg SQ every 12 hrsa Enoxaparin 0.5 mg/kg every 12 hrs Heparin 5000 units SQ every 8-12 hrsc Renal failure (CrCl < 30 mL/min)* *Not on renal replacement therapy Heparin 5000 units SQ every 8-12 hrsa Enoxaparin 30 mg SQ every 24 hrsb Obesity Class 3 (BMI > 40 kg/M2) Enoxaparin 40 mg SQ every 12 hrsb Heparin 5000 units SQ every 8 hrsb Low body weight (weight < 50 kg) Heparin 5000 units SQ every 8-12 hrsa Enoxaparin 30 mg SQ every 24 hrsc High Bleeding Risk Intermittent pneumatic compression devices (IPC)a Graduated compression stockings (GCS) or Venous foot pumps (VFP)c a: UW Health GRADE Moderate quality evidence, strong recommendation b: UW Health GRADE Low quality evidence, strong recommendation c: UW Health GRADE Low quality evidence, weak/conditional recommendation Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 15 Venous Thromboembolism Prophylaxis – Adult – Inpatient/Ambulatory Appendix B. VTE Prophylaxis in Surgical Patients Caprini Risk Assessment Model2,26 1 Point 2 Points 3 Points 5 Points Age 41-60 Age 61-74 Age ≥ 75 Acute spinal cord injury (< 1 mo) Acute MI (<1 mo) Central venous access Established thrombophilia Elective lower extremity arthroplasty BMI > 25 Immobile > 72 hrs HIT Hip, pelvis, or leg fracture (< 1 mo) CHF exacerbation (<1 mo) Leg plaster cast or brace Hx of VTE Stroke (< 1 mo) Hx of Inflammatory Bowel Disease Malignancy Family hx VTE (1 degree relative) Procedure with local anesthesia Surgery- arthroscopic Swollen legs or Varicose veins Surgery > 45 mins Sepsis (< 1 mo) Serious lung dx ex. Pneumonia (<1 mo) 1 point (For Women Only) Oral contraceptives or HRT Pregnancy or postpartum (< 1 month) Hx of unexplained stillborn infant, spontaneous abortion (≥3), premature birth with toxemia or growth restricted infant Points Risk Recommendation 0 Very Low VTE Risk Early and frequent ambulation 1-2 Low VTE Risk Mechanical Prophylaxis 3-4 Moderate VTE Risk and Low Bleed Risk Pharmacologic Prophylaxis > 5 High VTE Risk and Low Bleed Risk Mechanical AND Pharmacologic Prophylaxis > 2 High Bleed Risk Mechanical Prophylaxis VTE Prophylaxis Regimens for High VTE Risk General Surgery Patients2,12,13,15,16,20,27-34 Patient Population VTE Prophylaxis Regimens Preferred Option Alternative Option High VTE Risk Heparin 5000 units SQ every 8-12 hrsa Enoxaparin 40 mg SQ every 24 hrsa Renal impairment (CrCl < 30 mL/min)* *Not on hemodialysis Heparin 5000 units SQ every 8-12 hrsa Enoxaparin 30 mg SQ every 24 hrsb Bariatric Surgery Enoxaparin 40 mg SQ every 12 hrsa Heparin 5000 units SQ every 8-12 hrsc Major Trauma Enoxaparin 30 mg SQ every 12 hrsa Enoxaparin 0.5 mg/kg every 12 hrs Heparin 5000 units SQ every 8-12 hrsc Abdominal/Pelvic Surgery for Cancer Enoxaparin 40 mg SQ every 24 hrsb Heparin 5000 units SQ every 8-12 hrsc Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 16 High Bleed Risk Intermittent pneumatic compression devices (IPC)a Graduated compression stockings (GCS) or Venous foot pumps (VFP)c Cardiac Surgery Heparin 5000 units SQ every 8-12 hrs Enoxaparin 40 mg SQ every 24 hrs Craniotomy Intermittent pneumatic compression devices (IPC)a Graduated compression stockings (GCS) or Venous foot pumps (VFP)c Spinal Surgery Intermittent pneumatic compression devices (IPC)a Graduated compression stockings (GCS) or Venous foot pumps (VFP)c Thoracic Surgery Heparin 5000 units SQ every 8-12 hrs Enoxaparin 40 mg SQ every 24 hrs Trauma Surgery Enoxaparin 30 mg every 12 hrsa Enoxaparin 0.5 mg/kg every 12 hrs Heparin 5000 units SQ every 8-12 hrsc a: UW Health GRADE Moderate quality evidence, strong recommendation b: UW Health GRADE Low quality evidence, strong recommendation c: UW Health GRADE Low quality evidence, weak/conditional recommendation Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 17 Venous Thromboembolism Prophylaxis – Adult – Inpatient/Ambulatory Appendix C. VTE Prophylaxis in Orthopedic Surgery VTE prophylaxis regimens for orthopedic surgeries35-43 Standard VTE Risk Elevated VTE Risk High Bleed Risk Total Hip, Total Knee, or Shoulder Arthroplasty Apixaban 2.5 mg PO BIDa ASA 81 mg BID b ASA 325 mg QD - BID b Enoxaparin 40 mg SQ dailya Enoxaparin 30 mg SQ every 12 hrsa *Fondaparinux 2.5 mg daily b Rivaroxaban 10 mg PO dailya Warfarin (target INR 1.8-2.2) b Apixaban 2.5 mg PO BIDa Enoxaparin 30 mg SQ every 12 hrsa Enoxaparin 40 mg SQ dailya *Fondaparinux 2.5 mg daily b Rivaroxaban 10 mg PO dailya Warfarin (target INR 1.8-2.2) b Mechanical prophylaxis Hip Fracture Surgery All patients considered at elevated VTE risk: Apixaban 2.5 mg BID Enoxaparin 30 mg SQ every 12 hrsa Enoxaparin 40 mg Sq every 24 hrsa *Fondaparinux 2.5 mg daily b Rivaroxaban 10 mg PO dailya Warfarin (target INR 1.8-2.2) b Mechanical prophylaxis * May be considered for patients with heparin allergy a: UW Health GRADE Moderate quality evidence, strong recommendation b: UW Health GRADE Very Low quality evidence, strong recommendation Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 18 References 1. Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. Nov 2010;8(11):2450-7. doi:10.1111/j.1538-7836.2010.04044.x 2. Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. Feb 2012;141(2 Suppl):e227S- e277S. doi:10.1378/chest.11-2297 3. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence- Based Clinical Practice Guidelines. Chest. Feb 2012;141(2 Suppl):e195S-e226S. doi:10.1378/chest.11-2296 4. Forgione N, Deed G, Kilov G, Rigas G. Managing Obesity in Primary Care: Breaking Down the Barriers. Adv Ther. Feb 2018;35(2):191-198. doi:10.1007/s12325-017-0656-y 5. Garvey WT, Mechanick JI, Brett EM, et al. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITY. Endocr Pract. Jul 2016;22 Suppl 3:1-203. doi:10.4158/ep161365.Gl 6. Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest. Jan 2011;139(1):69-79. doi:10.1378/chest.09-3081 7. Rosenberg D, Eichorn A, Alarcon M, McCullagh L, McGinn T, Spyropoulos AC. External Validation of the Risk Assessment Model of the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) for Medical Patients in a Tertiary Health System. Journal of the American Heart Association. 2014;3(6):e001152-e001152. doi:10.1161/jaha.114.001152 8. Spyropoulos AC, Anderson FA, Jr., FitzGerald G, et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. Sep 2011;140(3):706-714. doi:10.1378/chest.10-1944 9. Germini F, Agnelli G, Fedele M, et al. Padua prediction score or clinical judgment for decision making on antithrombotic prophylaxis: a quasi-randomized controlled trial. J Thromb Thrombolysis. Oct 2016;42(3):336-9. doi:10.1007/s11239-016-1358-z 10. Nguyen GC, Sam J. Rising prevalence of venous thromboembolism and its impact on mortality among hospitalized inflammatory bowel disease patients. Am J Gastroenterol. Sep 2008;103(9):2272-80. doi:10.1111/j.1572-0241.2008.02052.x 11. Bernstein CN, Blanchard JF, Houston DS, Wajda A. The incidence of deep venous thrombosis and pulmonary embolism among patients with inflammatory bowel disease: a population-based cohort study. Thromb Haemost. Mar 2001;85(3):430-4. 12. King CS, Holley AB, Jackson JL, Shorr AF, Moores LK. Twice vs three times daily heparin dosing for thromboembolism prophylaxis in the general medical population: A metaanalysis. Chest. Feb 2007;131(2):507-16. doi:10.1378/chest.06-1861 13. Phung OJ, Kahn SR, Cook DJ, Murad MH. Dosing frequency of unfractionated heparin thromboprophylaxis: a meta-analysis. Chest. Aug 2011;140(2):374-381. doi:10.1378/chest.10-3084 14. Kierkegaard A, Norgren L. Graduated compression stockings in the prevention of deep vein thrombosis in patients with acute myocardial infarction. Eur Heart J. Oct 1993;14(10):1365-8. doi:10.1093/eurheartj/14.10.1365 15. Collaboration CT, Dennis M, Sandercock PA, et al. Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial. Lancet. Jun 6 2009;373(9679):1958-65. doi:10.1016/S0140-6736(09)60941-7 16. Muir KW, Watt A, Baxter G, Grosset DG, Lees KR. Randomized trial of graded compression stockings for prevention of deep-vein thrombosis after acute stroke. QJM. Jun 2000;93(6):359-64. doi:10.1093/qjmed/93.6.359 17. Heparin (Generic) [prescribing information]. Fresnius Kabi; Norway. 2017. 18. Enoxaparin (Lovenox®) [prescribing information]. Sanofi-Aventis; Bridgewater, NJ. 2009. Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 19 19. Nutescu EA, Spinler SA, Wittkowsky A, Dager WE. Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother. Jun 2009;43(6):1064-83. doi:10.1345/aph.1L194 20. Scholten DJ, Hoedema RM, Scholten SE. A comparison of two different prophylactic dose regimens of low molecular weight heparin in bariatric surgery. Obes Surg. Feb 2002;12(1):19-24. doi:10.1381/096089202321144522 21. Duplaga BA, Rivers CW, Nutescu E. Dosing and monitoring of low-molecular-weight heparins in special populations. Pharmacotherapy. Feb 2001;21(2):218-34. 22. Goldhaber SZ, Leizorovicz A, Kakkar AK, et al. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med. Dec 8 2011;365(23):2167-77. doi:10.1056/NEJMoa1110899 23. Cohen AT, Spiro TE, Buller HR, et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. Feb 7 2013;368(6):513-23. doi:10.1056/NEJMoa1111096 24. Cohen AT, Harrington RA, Goldhaber SZ, et al. Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients. N Engl J Med. Aug 11 2016;375(6):534-44. doi:10.1056/NEJMoa1601747 25. Spyropoulos AC, Ageno W, Albers GW, et al. Rivaroxaban for Thromboprophylaxis after Hospitalization for Medical Illness. N Engl J Med. Sep 20 2018;379(12):1118-1127. doi:10.1056/NEJMoa1805090 26. Bahl V, Hu HM, Henke PK, Wakefield TW, Campbell DA, Jr., Caprini JA. A validation study of a retrospective venous thromboembolism risk scoring method. Ann Surg. Feb 2010;251(2):344-50. doi:10.1097/SLA.0b013e3181b7fca6 27. Roderick P, Ferris G, Wilson K, et al. Towards evidence-based guidelines for the prevention of venous thromboembolism: systematic reviews of mechanical methods, oral anticoagulation, dextran and regional anaesthesia as thromboprophylaxis. Health Technol Assess. Dec 2005;9(49):iii-iv, ix- x, 1-78. 28. Urbankova J, Quiroz R, Kucher N, Goldhaber SZ. Intermittent pneumatic compression and deep vein thrombosis prevention. A meta-analysis in postoperative patients. Thromb Haemost. Dec 2005;94(6):1181-5. doi:10.1160/TH05-04-0222 29. Bartlett MA, Mauck KF, Daniels PR. Prevention of venous thromboembolism in patients undergoing bariatric surgery. Vasc Health Risk Manag. 2015;11:461-77. doi:10.2147/VHRM.S73799 30. Borkgren-Okonek MJ, Hart RW, Pantano JE, et al. Enoxaparin thromboprophylaxis in gastric bypass patients: extended duration, dose stratification, and antifactor Xa activity. Surg Obes Relat Dis. Sep-Oct 2008;4(5):625-31. doi:10.1016/j.soard.2007.11.010 31. Geerts WH, Jay RM, Code KI, et al. A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med. Sep 5 1996;335(10):701-7. doi:10.1056/NEJM199609053351003 32. Bush S, LeClaire A, Hampp C, Lottenberg L. Review of a large clinical series: once- versus twice- daily enoxaparin for venous thromboembolism prophylaxis in high-risk trauma patients. J Intensive Care Med. Mar-Apr 2011;26(2):111-5. doi:10.1177/0885066610384462 33. Ebeid A, Cole E, Stallwood-Hall C. The efficacy of weight-based enoxaparin dosing for venous thromboembolism prophylaxis in trauma patients: A systematic review and meta-analysis. J Trauma Acute Care Surg. Aug 1 2022;93(2):e71-e79. doi:10.1097/ta.0000000000003707 34. Verhoeff K, Raffael K, Connell M, et al. Relationship between anti-Xa level achieved with prophylactic low-molecular weight heparin and venous thromboembolism in trauma patients: A systematic review and meta-analysis. J Trauma Acute Care Surg. Aug 1 2022;93(2):e61-e70. doi:10.1097/ta.0000000000003580 35. Turpie AG, Lassen MR, Eriksson BI, et al. Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty. Pooled analysis of four studies. Thromb Haemost. Mar 2011;105(3):444-53. doi:10.1160/TH10-09-0601 36. Lassen MR, Gallus A, Raskob GE, et al. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med. Dec 23 2010;363(26):2487-98. doi:10.1056/NEJMoa1006885 37. Lassen MR, Raskob GE, Gallus A, et al. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. Mar 6 2010;375(9717):807-15. doi:10.1016/S0140-6736(09)62125-5 38. Eriksson BI, Bauer KA, Lassen MR, Turpie AG, Steering Committee of the Pentasaccharide in Hip- Fracture Surgery S. Fondaparinux compared with enoxaparin for the prevention of venous Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions 20 thromboembolism after hip-fracture surgery. N Engl J Med. Nov 1 2001;345(18):1298-304. doi:10.1056/NEJMoa011100 39. Bauer KA, Eriksson BI, Lassen MR, Turpie AG, Steering Committee of the Pentasaccharide in Major Knee Surgery S. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med. Nov 1 2001;345(18):1305-10. doi:10.1056/NEJMoa011099 40. Rivaroxaban (Xarelto®) [prescribing information]. Janssen Pharmaceuticals, Inc.; Leverkusen, Germany. 2019; 41. Apixaban (Eliquis®) [prescribing information]. Bristol-Myers Squibb Company.; Princeton, New Jersey. 2019; 42. Fondaparinux Sodium (Arixtra®) [prescribing information]. GlaxoSmithKline; Research Triangle Park, NC. 2010; 43. Falck-Ytter Y, Francis CW, Johanson NA, et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. Feb 2012;141(2 Suppl):e278S- e325S. doi:10.1378/chest.11-2404 44. Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. Feb 2012;141(2 Suppl):e24S-e43S. doi:10.1378/chest.11-2291 45. Wang TF, Milligan PE, Wong CA, Deal EN, Thoelke MS, Gage BF. Efficacy and safety of high-dose thromboprophylaxis in morbidly obese inpatients. Thromb Haemost. Jan 2014;111(1):88-93. doi:10.1160/TH13-01-0042 46. Beall J, Woodruff A, Hempel C, Wovkulich M, Zammit K. Efficacy and Safety of High-Dose Subcutaneous Unfractionated Heparin Prophylaxis for the Prevention of Venous Thromboembolism in Obese Hospitalized Patients. Hosp Pharm. May 2016;51(5):376-81. doi:10.1310/hpj5105-376 47. Joy M, Tharp E, Hartman H, et al. Safety and Efficacy of High-Dose Unfractionated Heparin for Prevention of Venous Thromboembolism in Overweight and Obese Patients. Pharmacotherapy. Jul 2016;36(7):740-8. doi:10.1002/phar.1775 48. Linkins LA, Dans AL, Moores LK, et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. Feb 2012;141(2 Suppl):e495S-e530S. doi:10.1378/chest.11-2303 49. Raftopoulos I, Martindale C, Cronin A, Steinberg J. The effect of extended post-discharge chemical thromboprophylaxis on venous thromboembolism rates after bariatric surgery: a prospective comparison trial. Surg Endosc. Nov 2008;22(11):2384-91. doi:10.1007/s00464-008-0031-9 50. Schmeler KM, Wilson GL, Cain K, et al. Venous thromboembolism (VTE) rates following the implementation of extended duration prophylaxis for patients undergoing surgery for gynecologic malignancies. Gynecol Oncol. Feb 2013;128(2):204-8. doi:10.1016/j.ygyno.2012.11.027 51. Mont MA, Jacobs JJ, Boggio LN, et al. Preventing venous thromboembolic disease in patients undergoing elective hip and knee arthroplasty. J Am Acad Orthop Surg. Dec 2011;19(12):768-76. 52. Ramacciotti E, Barile Agati L, Calderaro D, et al. Rivaroxaban versus no anticoagulation for post- discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial. The Lancet. 2022;399(10319):50-59. doi:10.1016/s0140- 6736(21)02392-8 53. COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at https://www.covid19treatmentguidelines.nih.gov/. Accessed February 8, 2023. 54. Gibson C, Spyropoulos A, Cohen A, et al. The IMPROVEDD VTE Risk Score: Incorporation of D- Dimer into the IMPROVE Score to Improve Venous Thromboembolism Risk Stratification. TH Open. 2017;01(01):e56-e65. doi:10.1055/s-0037-1603929 Copyright © 2023 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission. Contact: CCKM@uwhealth.org Last Revised: 03/2023 Effective 3/16/2023. Contact CCKM@uwhealth.org for previous versions