II. Precautions: Venous Thromboembolism Risk Reduction

  1. Early mobilization after surgery is critical
  2. Perioperative risk of VTE varies by surgery, Anesthesia
  3. Decision to anticoagulate is individualized to patients
    1. Does the risk of bleeding outweigh the VTE Risk
    2. Most non-surgical patients do not require DVT Prophylaxis after discharge (unless VTE or other indication)
      1. Minimal benefit and associated with bleeding risk
      2. Spyropoulos (2018) N Engl J Med 379(12):1118-27 [PubMed]

III. Approach: Perioperative Anticoagulation

  1. Anticoagulation start varies per medication and risk
  2. Continue Anticoagulation for at least 10 to 14 days post-orthopedic surgery
  3. Indications for extended Anticoagulation (28-35 days)
    1. Total hip replacement
    2. Hip Fracture
    3. Other risk factors
      1. Obesity
      2. Prior Venous Thromboembolism
      3. Immobility
      4. Advanced age
      5. Comorbid active malignancy

IV. Management: Perioperative protocol for the Highest Risk Patients

  1. Criteria
    1. Major surgery in high risk patient over age 40 years
      1. Venous Thromboembolism
      2. Cancer
      3. Thrombophilia
    2. Surgery at highest risk of Thromboembolism
      1. Hip or knee arthroplasty
      2. Hip Fracture surgery
      3. Major surgery
      4. Acute Spinal Cord Injury
  2. Management
    1. Anticoagulation options
      1. Low Molecular Weight Heparin
        1. Enoxaparin (Lovenox)
          1. Start: 40 mg SC 1-2 hours before surgery
          2. Then: 30 mg SC q12 hours (8-12 hours post-op)
        2. Dalteparin (Fragmin)
          1. Start: 5000 units SC 8-12 hours pre-op
          2. Then: 5000 units SC daily
      2. Warfarin with target INR 2-3
      3. Unfractionated Heparin 5000 units q8-12 hours
      4. Weight based Heparin nomogram
      5. Aspirin (not a first-line agent)
        1. Chest guidelines approved Aspirin for use as of 2012
          1. Total knee arthroplasty or total hip arthroplasty (as alternative agent)
        2. However, Low Molecular Weight Heparin is much more effective
          1. Prevents 11 more major VTE events than Aspirin per 1000 patients when used for 35 days
        3. Dose 162 mg daily for at least 10-14 days (preferably 35 days in hip or knee replacement)
          1. Some protocols use DOAC for the first 5 days, then Aspirin
        4. References
          1. (2012) Presc Lett 19(3): 16 [PubMed]
    2. Additional strategies (with Anticoagulation)
      1. Intermittent Pneumatic Compression Stockings or
      2. Graduated Compression Stockings or
      3. Foot and calf pumping devices
  3. Special circumstances: Prophylaxis after Total Knee Arthroplasty (TKA) or Total Hip Arthroplasty (THA)
    1. Duration of DVT Prophylaxis (may be adjusted for mobility)
      1. Total Hip Arthroplasty: 10-14 days
      2. Total Knee Arthroplasty: 35 days
    2. Low Molecular Weight Heparin (e.g. Enoxaparin or Lovenox)
      1. Gold standard Subcutaneous Injection therapy continued for 14 days after surgery (no monitoring needed)
    3. Apixaban (Eliquis)
      1. Dose 2.5 mg orally twice daily for 14 days
      2. Compared with LMWH, Apixaban has equivalent efficacy in DVT Prophylaxis
    4. Rivoroxaban (Xarelto)
      1. Dose: 10 mg orally once daily for 14 days (no monitoring needed)
      2. Compared with LMWH, prevents 4 more DVTs
      3. However is associated with 9 more serious bleeding events per 1000 patients
    5. Warfarin
      1. Indicated in Creatinine Clearance <30 ml/min in which DOACs are contraindicated
      2. Variable dosing orally for 14 days (requires monitoring)
      3. Compared with LMWH, prevents 3 fewer DVTs
      4. However is associated with 2 more fatal bleeding events per 1000 patients
    6. Aspirin
      1. Switch after 5 days on DOAC (e.g. Xarelto) and LMWH (e.g. Lovenox) to Aspirin
      2. Continue Aspirin 81 mg orally daily for at least 14 days, but preferably 35 days
      3. Consider in those without significant additional VTE Risks
        1. Do not use Aspirin prophylaxis in high risk patients (e.g. prior VTE, active cancer, immobile)
      4. References
        1. Anderson (2018) N Engl J Med 378(8):699-707 +PMID: 29466159
    7. Dabigatran (Pradaxa)
      1. Not available in appropriate 220 mg dose for VTE Prophylaxis in United States
    8. References
      1. (2014) Presc Lett 21(6): 31-2
      2. (2018) Presc Lett 25(5): 25
  4. Special circumstances: Hip Fracture protocol
    1. Fondaparinux is preferred
    2. Heparin or LMWH started pre-operatively
      1. Delay 12-24 hours post-op if bleeding high-risk
    3. Continue LMWH, Warfarin or Fondaparinux post-op
      1. Continue for at least 10-14 days after surgery
      2. Consider continuing for 28 to 35 days post-op
  5. Special circumstances: Elective hip surgery
    1. Lose weight before surgery
    2. Ambulation before the second post-surgical day
  6. Special circumstances: Gynecologic Surgery
    1. Unfractionated Heparin is the preferred agent

V. Management: Perioperative for High Risk Patients

  1. Criteria
    1. Patient with Thromboembolism risk and
      1. Age over 60 years and nonmajor surgery or
      2. Age over 40 years and major surgery
  2. Management
    1. Low Molecular Weight Heparin or
      1. Enoxaparin (Lovenox)
        1. Start: 40 mg SC 1-2 hours before surgery
        2. Then: 30 mg SC q12 hours (8-12 hours post-op)
      2. Dalteparin (Fragmin)
        1. Start: 5000 units SC 8-12 hours pre-op
        2. Then: 5000 units SC daily (12-24 hours post-op)
    2. Unfractionated Heparin 5000 units q8-12 hours or
    3. Intermittent Pneumatic Compression Stockings

VI. Management: Perioperative for Moderate Risk Patients

  1. Criteria
    1. Orthopedic Surgery (40-60% Thromboembolism risk)
    2. Thromboembolism risk and minor surgery
    3. No Thromboembolism risk
      1. Age over 60 years and nonmajor surgery or
      2. Age over 40 years and major surgery
  2. Management
    1. Low Molecular Weight Heparin
      1. Enoxaparin (Lovenox)
        1. 30 mg SC q12 hours (start 12-24 hours post-op) or
        2. 40 mg SC daily (start 12 hours post-op)
      2. Dalteparin (Fragmin)
        1. Start: 5000 units SC 8-12 hours pre-op
        2. Then: 5000 units SC daily (12-24 hours post-op)
      3. Tinzaparin (Innohep)
        1. Start: 3500 units SC 2 hours before surgery
        2. Then: 3500 units SC daily
    2. Unfractionated Heparin 5000 units q8-12 hours or
    3. Intermittent Pneumatic Compression Stockings

VII. Management: Perioperative for Low Risk Patients

  1. Criteria
    1. Minor surgery in age <40 and no Thromboembolism risk
  2. Management
    1. No Anticoagulation
    2. Early mobilization
    3. Consider graduated Compression Stockings

VIII. Management: Thromboprophylaxis in Critical Illness and Major Trauma

  1. Precautions
    1. Thromboprophylaxis assumes patient is hemodynamically stable without active bleeding (e.g. major Trauma)
    2. Start within 12-24 hours of major Trauma or when otherwise hemodynamically stable without active bleeding
    3. Most procedures (aside from Lumbar Puncture) can be performed without stopping Anticoagulation
      1. Prepare for planned procedures if holding Anticoagulation is required
  2. Pharmacologic Thromboprophylaxis
    1. Contraindications
      1. Active Hemorrhage
      2. Severe Thrombocytopenia (Platelet Count <30,000 or <50,000 and decreasing)
      3. Cirrhosis and increased INR is NOT a contraindication to Anticoagulation (unless actively bleeding)
    2. Low Molecular Weight Heparin (LMWH or Enoxaparin or Lovenox)
      1. Standard dose: 40 mg every 24 hours
      2. Very high VTE Risk: 30 mg SC every 12 hours
        1. Indications: Major Trauma or knee or hip surgery
      3. Low body weight (<50 kg): 30 mg SC every 24 hours
      4. Morbid Obesity (BMI >40 or weight >120 kg): 0.5 mg/kg every 24 hours
      5. Renal Failure (Creatinine Clearance <30 mg/dl): 30 mg once daily
        1. Consider Low dose Unfractionated Heparin (LDUH) instead
      6. Anti-Factor Xa Levels (monitored in pregnancy, weight outside norm, decreased Renal Function)
        1. Obtain Anti-Factor Xa Level 4 hours after third LMWH dose and expect 0.3 to 0.5 IU/ml
    3. Low dose Unfractionated Heparin (LDUH)
      1. Indications: Glomerular Filtration Rate <30 ml/min
      2. Contraindications: Hip or knee surgery
      3. Standard dose: 5000 units every 8 hours
      4. Modified dosing based on weight and BMI
        1. Weight <50 kg: 5000 units every 12 hours
        2. Weight >120 kg or BMI >50: Increase dose to 7500 units every 8 hours
  3. Mechanical Thromboprophylaxis
    1. Indications
      1. Alternative to Pharmacologic Thromboprophylaxis in patients who are bleeding or high risk of bleeding
    2. Efficacy
      1. Lower efficacy than Pharmacologic Thromboprophylaxis
      2. No additional benefit when added to Pharmacologic Thromboprophylaxis in critically ill patients
        1. Arabi (2019) N Engl J Med 380(14):1305-15 [PubMed]
    3. Methods
      1. Graded Compression Stockings (e.g. TED Stockings)
        1. Low efficacy compared with all other options
        2. Never recommended as single prophylaxis option
      2. Intermittent pneumatic compression (IPC)
        1. Applies intermittent compression pressures of 35 mmHg at ankle, 20 mmHg at thigh
        2. More effective than Graded Compression Stockings
        3. Indicated after surgeries at high risk of bleeding (e.g. craniotomy)
        4. Not well tolerated to awake, non-sedated patients
  4. References
    1. Marino (2014) The ICU Book, Wolters Kluwer, Philadelphia, p. 100-5
    2. Internet Book of Critical Care (Farkas, EM:Crit)
      1. https://emcrit.org/ibcc/guide/

IX. Management: Thromboprophylaxis in General Hospitalized Patients

  1. See above for Thromboprophylaxis in Critical Illness and Major Trauma
  2. Precautions
    1. Incidence of VTE 13 to 30% in those not receiving Thromboprophylaxis
  3. Indications
    1. Respiratory Failure
    2. Acute infection
    3. Active cancer
    4. Acute extremity paralysis, immobility or disuse
    5. Thrombophilia
    6. Autoimmune Conditions
    7. Inflammatory conditions
    8. Congestive Heart Failure history
    9. Venous Thromboembolism (VTE) history
    10. Renal Failure
    11. Intensive Care Unit Admission
  4. Contraindications
    1. High risk of bleeding
      1. Use Intermittent pneumatic compression (IPC) until patient is able to be anticoagulated
      2. Active Duodenal Ulcer
      3. Major bleeding event within prior 3 months of admission
      4. Intracranial Hemorrhage
      5. Scheduled invasive procedure
      6. Thrombocytopenia with Platelet Count <50 x10^3
    2. Anticoagulation not indicated
      1. Low risk patients
      2. Patient chronically anticoagulated (e.g. Atrial Fibrillation)
        1. Continue previously prescribed Anticoagulant
  5. Preferred Anticoagulants for Thromboprophylaxis in hospitalized patients
    1. Low Molecular Weight Heparin (LMWH, Lovenox)
      1. Give 40 units SQ daily (if BMI >=40 kg/m2, increase to twice daily)
      2. Overall preferred Anticoagulant for Thromboprophylaxis
    2. Low dose Unfractionated Heparin
      1. Give 5000 units every 8 to 12 hours SQ
      2. Preferred in renal Impairment
    3. Fondaparinux
      1. Give 2.5 mg SQ daily (if BMI >=40 kg/m2, increase to 5 mg daily)
      2. Preferred in Heparin Induced Thrombocytopenia (HIT) or NSTEMI
      3. Higher risk of bleeding than LMWH
  6. Other Anticoagulants for Thromboprophylaxis in hospitalized patients (esp. post-surgical)
    1. Precautions
      1. See specific agents for contraindications and precautions
      2. Avoid these agents in medically treated cancer patients
    2. Apixaban (Eliquis)
      1. Give 2.5 mg orally twice daily
      2. May be used in total hip and total knee arthroplasty
    3. Rivaroxaban
      1. Give 10 mg orally daily
      2. Avoid in Creatinine Clearance <30 ml/min and moderate to severe liver Impairment
    4. Dabigatran (Pradaxa)
      1. Start 110 mg postoperatively, then 220 mg daily
      2. Avoid in Creatinine Clearance <30 ml/min and moderate to severe liver Impairment

X. Management: Thromboprophylaxis in Casting

  1. Long leg cast above knee (especially in elderly)
    1. Kock (1995) 346:459-61 [PubMed]
  2. Lower leg cast
    1. Typically does not require DVT Prophylaxis in most cases
      1. van Adrichem (2017) N Engl J Med 376(6): 515-25 +PMID:27959702 [PubMed]
    2. Exceptions in which DVT Prophylaxis is appropriate in lower leg Casting
      1. History of prior Venous Thromboembolism
      2. Achilles Tendon Rupture (controversial)
      3. Long distance air travel >6 hours planned
        1. Cesarone (2002) Angiology 53(1): 1-6 +PMID:11863301 [PubMed]
    3. References
      1. Orman, DeLoughery and Ramadorai in Herbert (2017) EM:Rap 17(7): 13-4

XI. Management: Venous Thromboembolism Prevention in Cancer

  1. Indications
    1. Active Solid Tumor or Lymphoma AND
    2. Khorona Score >=3 (associated with 6-7% risk of VTE in next 2.5 months)
      1. https://www.mdcalc.com/khorana-risk-score-venous-thromboembolism-cancer-patients
  2. Contraindications
    1. Increased bleeding risk (e.g. HAS-BLED Score)
    2. Platelets <50,000
    3. Significantly decreased Life Expectancy
  3. Preparations used for prophylaxis in cancer
    1. Eliquis 2.5 mg orally twice daily
    2. Xarelto
    3. Low Molecular Weight Heparin (Enoxaparin or Lovenox)
  4. References
    1. (2020) Presc Lett 27(6): 32-3

XII. Resources

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