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TITLE VENOUS THROMBOEMBOLISM PROPHYLAXIS SCOPE Provincial Acute and Sub-Acute Care Facilities APPROVAL AUTHORITY Alberta Health Services Executive Committee SPONSOR Vice President, Quality and Chief Medical Officer Venous Thromboembolism Prophylaxis Policy (#PS-09) DOCUMENT # PS-09-01 INITIAL EFFECTIVE DATE August 29, 2012 REVISION EFFECTIVE DATE SCHEDULED REVIEW DATE December 01, 2019 NOTE: The first appearance of terms in bold in the body of this document (except titles) are defined terms please refer to the Definitions section. If you have any questions or comments regarding the information in this document, please contact the Policy & Forms Department at policy@ahs.ca. The Policy & Forms website is the official source of current approved policies, procedures, directives, standards, protocols and guidelines. OBJECTIVES To outline the recommended approach to venous thromboembolism (VTE) prophylaxis for all patients admitted to an Alberta Health Services acute and sub-acute care facility. Clinical judgment may be exercised when a situation is determined to be outside the parameters provided in this guideline. If a deviation from this guideline is determined to be appropriate or necessary, documentation of the rationale shall be included on the patient s health record. PRINCIPLES The underlying principle guiding the use of thromboprophylaxis in Alberta Health Services is that all acute and sub-acute care patients at risk receive thromboprophylaxis. An assessment of risk of venous thromboembolism and bleeding risk should be made by the most responsible health practitioner at the time of admission to an acute and/or sub-acute care facility. All health care professionals should identify patients who are at risk that are not receiving thromboprophylaxis or whose bleeding risk has subsided. This information is to be provided to the patient s health care team immediately. APPLICABILITY Compliance with this document is required by all Alberta Health Services employees, members of the medical and midwifery staffs, Students, Volunteers, and other persons acting on behalf of Alberta Health Services (including contracted service providers as necessary) working in Acute Care and Sub-Acute Facilities. Alberta Health Services (AHS) PAGE: 1 OF 17

ELEMENTS The approach to thromboprophylaxis in Alberta Health Services involves three steps: Step 1 Is Thromboprophylaxis NOT INDICATED? 1.1 For patients who are fully mobile and expected to have a length of stay less than 48 hours, thromboprophylaxis is generally not needed unless multiple other venous thromboembolism risk factors are present. 1.2 If no specific thromboprophylaxis is provided, patients should be encouraged to be as mobile as possible. 1.3 If a patient s clinical status changes significantly, a decision about thromboprophylaxis should be reassessed at that time. 1.4 For patients whose goals of care designation is Medical Care and Interventions, Focused on Comfort, anticoagulant prophylaxis is not given. See Alberta Health Services Advance Care Planning and Goals of Care Designation Policy and Procedure. Step 2 Is Anticoagulant Thromboprophylaxis CONTRAINDICATED? 1.1 Absolute contraindications to anticoagulant thromboprophylaxis are: a) active, clinically-important bleeding; b) platelets less than 30 x 10 9 /L; and/or c) major bleeding disorder. 1.2 Relative contraindications to anticoagulant thromboprophylaxis are: a) recent intracranial haemorrhage; b) recent paraspinal bleeding; and/or c) recent high-risk bleeding surgery. 1.3 For patients who are actively bleeding or have a high risk of bleeding, anticoagulant prophylaxis is not given. In this situation, intermittent pneumatic compression devices or bilateral, properly measured and fitted, calf-length graduated compression stockings are placed. a) These patients should be reassessed daily for proper use of the stockings/compression device and bleeding risk. When the high bleeding risk decreases, anticoagulants should be started. Alberta Health Services (AHS) PAGE: 2 OF 17

b) High Bleeding Risk Considerations in Hospitalized Patients: (i) peptic ulcer disease *; (ii) prior bleeding history *; (iii) thrombocytopenia *; (iv) (v) (vi) (vii) (viii) (ix) hepatic failure; rheumatic diseases; current cancer; age; renal failure; and/or Intensive Care Unit / Cardiac Care Unit stay. Note: * indicates high bleeding risk, either as a single factor or associated with other risk factors. 1.4 For patients with heparin-induced thrombocytopenia (HIT), either currently or in the past, unfractionated heparin (UFH) or low molecular weight heparin (LMWH) is contraindicated. In this setting, the internal medicine or haematology service should be contacted for advice the most appropriate anticoagulant thromboprophylaxis in the setting of heparin-induced thrombocytopenia is generally fondaparinux 2.5 milligrams (mg) subcutaneously (SC) once daily or intravenous argatroban. a) In order to avoid the higher risk of heparin-induced thrombocytopenia, use of unfractionated heparin should be minimized. 2.1 Assess risk of thromboembolism based on known risk factors: a) Major risk factors for thromboembolism: (i) (ii) (iii) (iv) (v) active cancer and its treatment; ischemic stroke or paralysis; trauma (especially of abdomen, pelvis and/or lower extremity); age greater than 75 years; major surgery (especially of abdomen, pelvis and/or lower extremity); Alberta Health Services (AHS) PAGE: 3 OF 17

(vi) congenital and/or acquired thrombophilia states; (vii) (viii) (ix) prior venous thromboembolism; intubated and mechanically ventilated; and/or spinal cord injury. b) Minor risk factors for Venous Thromboembolism: (i) (ii) (iii) (iv) (v) (vi) (vii) (viii) (ix) (x) (xi) (xii) (xiii) (xiv) (xv) age 60 to 74 years; general anesthesia greater than one (1) hour; obesity; sepsis; collagen vascular disease; inflammatory bowel disease; postpartum (six [6] weeks); severe respiratory disease; congestive heart failure; myeloproliferative disorders; pregnancy; varicose veins; estrogen therapy; nephrotic syndrome; and/or prolonged immobility greater than 24 hours. 2.2 See Table 1: Levels of Thromboembolism Risk and Recommended Thromboprophylaxis in Hospital Patients. Alberta Health Services (AHS) PAGE: 4 OF 17

Table 1 Levels of Thromboembolism Risk and Recommended Thromboprophylaxis in Hospital Patients. Level of venous thromboembolism risk (approximate deep vein thrombosis risk without prophylaxis) Low (Less than 10%) Risk Factors for venous thromboembolism Expected length of stay less than 72 hours Minor surgery Mobile medical Patient Suggested thromboprophylaxis options Early ambulation Moderate (10-40%) High (40-60%) Very High (40-80%) High bleeding risk Age less than 60 years Most general, gynaecology or urological surgery patients Immobilized medical patients Age greater than 75 years Major or multiple minor risk factors for venous thromboembolism Major abdominal surgery Major trauma Spinal cord injury Major cancer surgery Hip fracture Hip arthroplasty Knee arthroplasty low molecular weight heparin low dose unfractionated heparin bid or tid fondaparinux low molecular weight heparin low dose unfractionated heparin tid fondaparinux low molecular weight heparin Consider extended prophylaxis Vitamin K Antagonists Also Consider: fondaparinux Also Consider: rivaroxaban apixaban (Anti-Xa inhibitors) Mechanical prophylaxis with intermittent pneumatic compression Alberta Health Services (AHS) PAGE: 5 OF 17

DEFINITIONS TITLE EFFECTIVE DATE DOCUMENT # 2.3 For most patients, the recommended anticoagulant thromboprophylaxis is low molecular weight heparin once daily. a) In general, for weight less than 40 kilograms, it is recommended that a dose reduction be considered. b) In general, for weight greater than 100 kilograms (and body mass index [BMI] greater than 35), it is recommended that a dose increase be considered. For weight greater than 120 kilograms, even higher doses should be considered. c) A dosage reduction is recommended for prophylactic doses of low molecular weight heparins for patients with severe renal impairment (creatinine clearance [CrCl] less than 20-30 millilitres/minute [ml/min]). For patients with creatinine clearance less than 20 ml/min, low dose unfractionated heparin prophylaxis is preferred over low molecular weight heparin. d) For arthroplasty patients, the first dose of low molecular weight heparin is generally given six (6) hours post-operatively and then daily. e) If patients are already receiving low molecular weight heparin and are scheduled for an epidural insertion, it is recommended that the anticoagulant be held for 18 to 24 hours prior to insertion. f) For patients with epidural catheters, the low molecular weight heparin dose is held to facilitate catheter removal in the morning and to allow for at least 18 hours after the previous low molecular weight heparin dose before catheter removal. For patients who have had an epidural catheter removed, the next dose of low molecular weight heparin should be delayed for at least two (2) hours after removal. Deep vein thrombosis means a thrombus ( blood clot ) occurring in one or more deep veins, especially in the legs, where it may produce leg swelling and/or pain. Goals of care designation means a codified instruction that provides direction regarding general care intentions, specific health interventions, transfer decisions and locations of care, for a patient as established after consultation between the most responsible health practitioner, patient and when appropriate, alternate decision-maker. Health care professional means an individual who is a member of a regulated health discipline, as defined by the Health Disciplines Act (Alberta) or the Health Professions Act (Alberta), and who practises within scope or role. Most responsible health practitioner means the health practitioner who has responsibility and accountability for the specific treatment/procedure(s) provided to a patient and who is Alberta Health Services (AHS) PAGE: 6 OF 17

authorized by Alberta Health Services to perform the duties required to fulfill the delivery of such a treatment/procedure(s) within the scope of his/her practice. Patient means an adult or child who receives or has requested health care or services from Alberta Health Services and its health care providers or individuals authorized to act on behalf of Alberta Health Services. This term is inclusive of residents, clients and outpatients. Thromboprophylaxis means the use of mechanical methods or anticoagulant medication to prevent venous thromboembolism from developing in patients who are at risk. Venous thromboembolism (VTE) means a thromboembolic event ( blood clot ) that develops within the venous system and includes both deep vein thrombosis and pulmonary embolism. REFERENCES Appendix A: Recommended Thromboprophylaxis Therapy by Patient Group Appendix B: Thromboprophylaxis Pharmacologic Dosing in Patients with Reduced Renal Function or Extremes of Weight Alberta Health Services Governance Documents o Advance Care Planning and Goals of Care Designation Policy and Procedure (#HCS - 38) o Venous Thromboembolism Prophylaxis Policy (#PS-09) VERSION HISTORY Date November 17, 2012 Action Taken Non-substantive change Revised Alberta Health Services (AHS) PAGE: 7 OF 17

APPENDIX A Recommended Thromboprophylaxis Therapy by Patient Group General Considerations: 1. Although the recommended options apply to most patients in each group, individual patient factors may suggest an alternate approach. 2. For all patients in whom it is possible and appropriate, early and frequent mobilization and ambulation are essential. 3. In general, for weight less than 40 kg or creatinine clearance less than 30 ml/min, it is suggested that the prophylactic low molecular weight heparin dose be reduced to the next lower pre-filled syringe dose for enoxaparin only. In general, for weight greater than 100 kg (and body mass index [BMI] greater than 35), consider doubling the low molecular weight heparin dose. At weights greater than 120 kg, even higher doses should be considered. 4. The duration of thromboprophylaxis is not based on pre-hospitalization mobility status alone. Given evidence suggesting low to moderate bleeding risk associated with use of prophylactic dosages of low molecular weight heparin, in absence of clinically significant bleeding or in setting of procedures involving critical areas where achieving hemostasis is limited or potentially catastrophic bleeding is possible, in most instances, thromboprophylaxis should not be withheld.[bump, 2008] Alberta Health Services (AHS) PAGE: 8 OF 17

Patient group Recommended Thromboprophylaxis Option High bleeding risk Intermittent pneumatic compression graduated compression stockings used continuously (except for bathing or ambulating) Neuraxial blockade / spinal anaesthesia Heparin-induced thrombocytopenia (HIT) unfractionated heparin bid/tid Can use low molecular weight heparin after epidural removed Suggest haematology / internal medicine consult No heparin or low molecular weight heparin fondaparinux 2.5 mg SC once daily (previous heparin-induced thrombocytopenia) argatroban IV (current heparin-induced thrombocytopenia) Initiation ASAP after emergency admission Just prior to surgery for elective surgical procedures unfractionated heparin hold 12-24 hours prior to procedure and hold four (4) hours post procedure low molecular weight heparin hold 18-24 hours prior to procedure and hold four (4) hours post procedure As soon as the diagnosis of heparin-induced thrombocytopenia considered Duration Until bleeding risk allows the use of anticoagulants Discharge and platelet count greater than 120 x 10 9 /L Alberta Health Services (AHS) PAGE: 9 OF 17

Patient group Recommended Thromboprophylaxis Option Burn unit patients low molecular weight heparin every 24 hours or low dose unfractionated heparin bid/tid Cardiovascular surgery Chronic kidney disease Critical care low molecular weight heparin every 24 hours or low dose unfractionated heparin bid/tid Initiation When there is evidence of primary hemostasis Primary hemostasis Duration unfractionated heparin bid/tid On admission Use Critical Care order sets In most cases, the prophylaxis is low molecular weight heparin every 24 hours or low dose unfractionated heparin bid/tid graduated compression stockings until anticoagulants can be started First dosing time after admission, if possible See Critical Care order sets Include thromboprophylaxis in transfer orders Alberta Health Services (AHS) PAGE: 10 OF 17

General surgery (major) Use General Surgery order sets In most cases, the prophylaxis is low molecular weight heparin every 24 hours or low dose unfractionated heparin bid/tid graduated compression stockings until low molecular weight heparin can be started Zero one (0-1) hour pre-op (if no epidural) or Four (4) hours after insertion of epidural Post-op day one if bleeding concerns Consider extended prophylaxis for abdominopelvic cancer surgeries Gynaecology Use Gynaecology order sets In most cases, the prophylaxis is low molecular weight heparin every 24 hours or low dose unfractionated heparin bid/tid graduated compression stockings or until anticoagulants can be started First dosing time after emergency room admission or post-op or The following morning if there are bleeding concerns Consider extended prophylaxis for abdominopelvic cancer surgeries Alberta Health Services (AHS) PAGE: 11 OF 17

Hip & knee arthroplasty Use Arthroplasty order sets In most cases, the prophylaxis is low molecular weight heparin every 24 hours For patients with moderate renal dysfunction, use dose reduced low molecular weight heparin SC every 24 hours or low dose unfractionated heparin bid Six-eight (6 8) hours post-op 15 days 28 days if higher risk and total hip replacement Or fondaparinux or rivaroxaban/apixaban or vitamin K antagonist Hip fracture Use Hip Fracture admission and postop order sets low molecular weight heparin every 24 hours or fondaparinux or warfarin If surgery is delayed, start low molecular weight heparin on admission 28 35 days Dosage reduction if weight less than 40 kg or creatinine clearance less than 30 ml/min Alberta Health Services (AHS) PAGE: 12 OF 17

Internal medicine (and medical subspecialties) Use Medicine admission order sets / deep vein thrombosis prophylaxis order sets For most Patients, low molecular weight heparin every 24 hours First dosing time after admission Consider extended for cancer, stroke or low dose unfractionated heparin bid/tid or fondaparinux Dosage adjustment for high or low weight and renal dysfunction graduated compression stockings until anticoagulant can be started Neurosurgery graduated compression stockings until anticoagulant can be started low molecular weight heparin every 24 hours or low dose unfractionated heparin bid/tid or start with intermittent pneumatic compression / bilateral calf-length graduated compression stockings and switch to low molecular weight heparin when risk of bleeding decreases For intermittent pneumatic compression/graduated compression stockings, start just prior to surgery for elective surgical procedure and ASAP after admission for major neurotrauma or non-traumatic intracranial haemorrhage For low molecular weight heparin, no sooner than day after surgery Alberta Health Services (AHS) PAGE: 13 OF 17

Obstetrics low molecular weight heparin every 24 hours Oncology (medical and radiation) Paediatrics low molecular weight heparin every 24 hours graduated compression stockings until low molecular weight heparin can be started Early mobilization except in very high risk population No clear evidence supporting thromboprophylaxis in paediatric population Plastic surgery low molecular weight heparin, every 24 hours, fondaparinux, low dose unfractionated heparin bid/tid Initial dose of unfractionated heparin given immediately post caesarean for high risk individuals low molecular weight heparin started at least two (2) hours after epidural removed First dosing time after admission Pre-op or post-op six-twelve (6-12) hours Extended for six (6) weeks and/or converted to warfarin for those with prior venous thromboembolism or with thrombophilia Consider benefits vs. risk of post-discharge or extended thromboprophylaxis Alberta Health Services (AHS) PAGE: 14 OF 17

Spinal cord injury low molecular weight heparin every 12 or 24 hours Spine surgery low molecular weight heparin every 24 hours Stroke ischemic Stroke haemorrhagic Use Stroke admission order sets For most patients, low molecular weight heparin every 24 hours Dosage adjustment for low or high weight and renal dysfunction graduated compression stockings until low molecular weight heparin can be started Use Stroke admission order sets Intermittent pneumatic compression or bilateral, properly-fitted, calf-length graduated compression stockings After approximately five seven (5 7) days, consider switch to low molecular weight heparin as for ischemic stroke ASAP after admission (once hemostasis is evident) Evening or morning after surgery First dosing time after admission On admission from rehab, consider extended prophylaxis six-twelve (6-12) weeks Consider extended prophylaxis for hemiplegia for sixtwelve (6-12) weeks Alberta Health Services (AHS) PAGE: 15 OF 17

Sub-acute care low molecular weight heparin every 24 hours or low dose unfractionated heparin bid Trauma Urology For extended prophylaxis in spinal cord injury, stroke associated with paralysis, hip fracture or total joint and abdominal/pelvic cancer therapy graduated compression stockings until low molecular weight heparin can be started Usual risk patients: low molecular weight heparin every 24 hours High risk patients (lower extremity fracture): low molecular weight heparin every 12 hours Use Urology order sets In most cases, the prophylaxis is low molecular weight heparin every 24 hours or low dose unfractionated heparin bid graduated compression stockings until low molecular weight heparin can be started Continuation of prophylaxis at transitions ASAP after admission (once hemostasis is evident) Options: First dosing time after surgery Morning after surgery if there are bleeding concerns First dosing time after emergency room admission or post-op 10 35 days from rehabilitation Alberta Health Services (AHS) PAGE: 16 OF 17

Drug Thromboprophylaxis Pharmacologic Dosing in Patients with Reduced Renal Function or Extremes of Weight Reduced renal function Creatinine Clearance less than 30 ml/min Obesity Weight greater than 100 kg (and BMI greater than 35) Low weight Weight less than 40 kg enoxaparin 20-30 mg subcutaneously daily 40-60 mg subcutaneously twice daily 20-30 mg subcutaneously daily APPENDIX B dalteparin 2500-5000 units subcutaneously daily 7500 units subcutaneously daily 2500 units subcutaneously daily tinzaparin No adjustment 75 units/kg subcutaneously daily 75 units/kg subcutaneously daily unfractionated heparin 5000 units subcutaneously twice daily 5000 units subcutaneously every eight (8) hours 5000 units subcutaneously twice daily Note: Monitoring anti-xa levels may be useful in selected patients. Note: At weights greater than 120 kg, even higher doses should be considered. Alberta Health Services (AHS) PAGE: 17 OF 17