Perioperative Thromboembolism Prophylaxis

Fundamentals of Thromboembolism Prophylaxis

• Key Concept:
• Any surgical procedure activates the coagulation system, leading to hypercoagulability.
• Surgical Risk Levels:
• Low Risk:
  • Short procedures (<45 minutes), minimal trauma, low soft tissue damage, no additional risk factors.
• Moderate Risk:
  • General surgical procedures lasting >45 minutes.
  • Low-risk procedures with additional patient risk factors.
  • Immobilization of the lower limbs.
• High Risk:
  • Polytrauma, pelvic, knee, hip, or spinal surgery.
  • Major thoracic, abdominal, or pelvic operations for malignancies or inflammatory diseases.
  • Moderate-risk procedures in patients with additional risk factors.
  • History of thrombosis or pulmonary embolism.

Risk Factors

• Genetic and Acquired Factors:
• Genetic: Factor V Leiden, prothrombin mutation, antithrombin III deficiency, protein C/S deficiency.
• Acquired: Antiphospholipid syndrome, dehydration, estrogen therapy, smoking, malignancy (especially abdominal).
• Other Risk Factors:
• Thrombosis history, heart failure (NYHA III/IV), systemic infections/SIRS, pregnancy, postpartum period, chronic venous insufficiency, nephrotic syndrome, obesity, age >50 years.

Thromboembolism Incidence Without Prophylaxis

Therapeutic Strategies

• Short-Term Therapy:
• Immediate treatment with heparin for any indication.
• Long-Term Therapy:
• Venous indications: Coumarin derivatives.
• Arterial indications: Antiplatelet agents may also be used.

Adjunctive Measures

• For Venous Thrombosis Prevention:
• Early mobilization, active movement.
• Appropriately fitted compression stockings applied before surgery to prevent intraoperative microthrombosis.
• If pre-made stockings are unsuitable, use venous compression bandages.
• For Arterial Thrombosis Prevention:
• Maintain normal blood pressure.

General Indications for Thromboembolism Prophylaxis

• Hospitalized Patients:
• All admitted patients and those undergoing ambulatory surgery with prolonged bed rest.
• Exceptions: Minor procedures on extremities or superficial trunk surgeries.
• Immobilization or Trauma:
• After injuries or cardiovascular diseases.
• Recurrence Prevention:
• Following pulmonary embolism or deep vein thrombosis.
• After venous thrombectomy or surgeries on the venous system.
• Arterial Thrombosis Prevention:
• After arterial procedures, small vessel anastomoses, arterial replacements with prosthetics, artificial heart valves, stents, or PTA.
• Recurrence Prevention After Arterial Embolism:
• Following arterial embolectomy.

Heparin in Perioperative Thromboembolism Prophylaxis

Key Information

• Mechanism of Action:
• Heparin works by activating antithrombin III (AT-III).
• In cases of AT-III deficiency (<70%), heparin’s efficacy is reduced.
  • Management: Substitute AT-III or increase heparin dosage until PTT/TZ is in the therapeutic range.

Indications

• Prophylactic Heparinization (Low-Dose):
• Immobility, post-surgical or trauma recovery, cardiovascular conditions.
• Therapeutic Heparinization (High-Dose):
• Thromboembolic diseases, extracorporeal circulation (e.g., dialysis), acute coronary syndrome, post-heart valve replacement, disseminated intravascular coagulation (DIC).

Contraindications

Prophylactic Heparinization

• Heparin allergy, Heparin-induced thrombocytopenia type II (HIT II).

Therapeutic Heparinization

• Bleeding diathesis, active bleeding, coagulation factor deficiency, severe thrombocytopenia, GI ulcers, esophageal varices, bronchiectasis, malignancies, severe hypertension (diastolic BP >105 mm Hg), severe atherosclerosis, significant liver/kidney/pancreatic insufficiency, bacterial endocarditis, retinal disorders, CNS surgeries/trauma, spinal/peridural anesthesia, lumbar punctures, arterial or organ punctures, imminent abortion.

Special Considerations

• Renal Insufficiency: Avoid low molecular weight heparin (LMWH) due to accumulation risks. Use unfractionated heparin (UFH) instead.
• HIT II Monitoring:
• Regular platelet counts (e.g., every 5 days).
• Diagnosed using the HIPA test (Heparin-induced platelet activation test).
• Management: Stop heparin immediately, consider alternative agents like Lepirudin.

Side Effects

• Heparin-Induced Thrombocytopenia (HIT):
• Type I (Non-Immunologic):
  • Early onset (1–2 days post-administration), mild thrombocytopenia.
  • Reversible, can continue heparin.
• Type II (Immunologic):
  • Late onset (5–14 days post-administration), significant thrombocytopenia (<80,000/µl).
  • Complications: “White clot syndrome,” high mortality with thromboembolic events.
  • Management: Discontinue heparin; use alternatives.
• Bleeding:
• Management:
  • Stop heparin for mild bleeding.
  • Use protamine sulfate for severe bleeding (1 ml neutralizes 1000 IU heparin).
• Other Side Effects:
• Allergic reactions, elevated liver enzymes, alopecia, headaches, osteoporosis (long-term use).

Dosage and Administration

Prophylactic Heparinization (Low-Dose)

Therapeutic Heparinization (High-Dose)

Monitoring and Antagonism

• Therapy Monitoring:
• Use PTT (Partial Thromboplastin Time) and TZ (Thrombin Time).
• Therapeutic PTT: 1.5–2.5× baseline.
• Therapeutic TZ: 60 seconds.
• Antagonist for Bleeding:
• Protamine Sulfate: 1 ml neutralizes 1000 IU UFH.
• Start with 5 ml protamine, followed by PTT monitoring.
• Side Effects: Allergic reactions, hypotension, pulmonary hypertension.

Key Points

• Only UFH can be administered intravenously.
• Adjust doses for obese patients based on body weight.
• Prophylactic heparin reduces the risk of DVT by ~67% and PE by ~50%.

Coumarin Derivatives

Mechanism of Action

• Action: Competitively antagonizes vitamin K, reducing the synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X (as well as proteins C and S) in the liver.

Indications

• Long-Term Anticoagulation:
• Post-thromboembolic events (e.g., deep vein thrombosis (DVT), pulmonary embolism (PE), stroke).
• Increased risk of thromboembolic complications (e.g., atrial fibrillation, heart valve replacement, left ventricular thrombus, prolonged immobilization).
• Note: Perioperative thrombosis prophylaxis is generally performed with heparin due to the increased bleeding risk associated with coumarin therapy.

Contraindications

• General Contraindications:
• Heparin-induced thrombocytopenia (HIT II), pregnancy (teratogenic), lactation, epilepsy, poor patient compliance.
• Additional Contraindications for Long-Term Use:
• Absolute: Pregnancy, active bleeding, severe liver/kidney disease, untreated infections, and more (see therapeutic heparinization contraindications).
• Relative: Epilepsy, poor patient compliance, and other conditions.

Side Effects

• Common Side Effects:
• Bleeding, appetite loss, nausea, diarrhea, skin necrosis, urticaria, dermatitis, reversible alopecia, elevated liver enzymes.
• Monitoring:
• Regular INR and Quick tests are required to adjust dosage and minimize risks.

Key Points

• Drug Interactions:
• Coumarins interact with many other drugs. Always check drug interactions before administering any new medication.
• Patient Education:
• Before initiating therapy, patients must be thoroughly informed about risks and potential side effects. Provide a patient pass.

Commonly Used Preparations

• Example: Phenprocoumon (e.g., Marcumar) 3 mg/tablet, Half-life 6.2 days.

Dosing Guidelines

• Initial Dosing:
• Day 1: 3 tablets = 9 mg.
• Day 2: 2 tablets = 6 mg.
• Day 3: 1 tablet = 3 mg.
• Maintenance Dosing:
• Adjust according to INR or Quick values (see below).
• Typically, 1/2 to 1 1/2 tablets daily (take in the evening).
• Special Considerations:
• In elderly patients (≥60 years) or those with renal insufficiency, start with 2 tablets.

Monitoring and Dose Adjustment

• INR (International Normalized Ratio):
• Aiming for an INR of 2.0–3.0.
• For mechanical heart valves, aim for INR of 3.25.
• For myocardial infarction, aim for INR of 3.0.
• Quick (Thromboplastin Time, TPZ):
• Normal range: 70–100%.
• Therapeutic range: 35–23%.

Duration of Therapy

Overdose Management

• Action: Pause therapy and monitor Quick daily until therapeutic range is reached.
• When Quick is <12% (INR >5):
• Administer Vitamin K (e.g., Konakion MM) 5–10 mg orally or intravenously.
• Effects appear after 8–12 hours.
• Maximum Vitamin K Dose:
• Single dose: 20 mg, total dose: 40 mg.
• For Life-Threatening Bleeding:
• Administer PPSB (Plasma Prothrombin Complex Concentrate) or 1–2 units of FFP (Fresh Frozen Plasma), along with 10 mg Vitamin K (1 ampule) slowly IV.

Antiplatelet Agents

Indications

• Conditions Treated:
• Coronary artery disease (CAD)
• Post-myocardial infarction (MI)
• Acute coronary syndrome (ACS)
• Post-ischemic cerebral stroke
• Peripheral arterial disease (PAD)
• Post-vascular surgical procedures

Acetylsalicylic Acid (Aspirin)

• Dosage: 100 – 300 mg/day orally.
• First-line therapy for the above conditions.
• Contraindications and Side Effects: See Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) section (p. 87).

Thienopyridines (Alternative for Aspirin Intolerance)

• Clopidogrel (Plavix, Iscover):
• Dosage: 75 mg/day orally.
• Contraindications: Coagulation disorders, head trauma (SHT), allergy, GI ulcers, pregnancy, lactation.
• Side Effects: Bleeding, gastrointestinal disturbances, skin rash, liver dysfunction.
• Ticlopidine (Tiklyd):
• Dosage: 250 mg twice daily orally.
• Indication: Used before the approval of Clopidogrel for treatment initiation. Note: Ticlopidine is now largely replaced by Clopidogrel, but should not be switched for previously well-treated patients.
• Side Effects: Neutropenia.

GPIIb/IIIa Antagonists

• Drugs:
• Abciximab (ReoPro):
  • Initial Dose: 0.25 mg/kg body weight as an intravenous bolus.
  • Maintenance Dose: 0.125 µg/kg body weight/min intravenously for 12 hours post-procedure.
• Tirofiban (Aggrastat):
  • Initial Dose: 0.4 µg/kg body weight/min over 30 minutes.
  • Maintenance Dose: 0.1 µg/kg body weight/min intravenously for 12–24 hours post-procedure.
• Indications:
• High-risk percutaneous coronary interventions (PTCA).
• Acute coronary syndrome.
• Used in combination with heparin and aspirin.
• Contraindications:
• Active internal bleeding, hypersensitivity to components or monoclonal antibodies, recent major surgery or trauma within the last 2 months.
• Intracranial tumors, cerebrovascular complications in the last 2 years, AV malformations, aneurysms, hemorrhagic diathesis, thrombocytopenia.
• Severe liver or kidney dysfunction, coagulation disorders (e.g., with warfarin), vasculitis, uncontrolled hypertension, retinopathy.
• Side Effects:
• Bleeding, hypotension, nausea, bradycardia, fever, thrombocytopenia.

Pragmatic Approach to Perioperative Thromboembolism Prophylaxis

Routine Prophylaxis for Most Patients

• Low-Molecular-Weight Heparin (NMH):
• Dosage: Refer to Table 4.4.
• First dose administered the evening before the surgery, followed by a second dose after surgery, and then daily doses until full mobilization is achieved.

After Major Surgeries and/or for Intensive Care Patients

• Unfractionated Heparin (UFH):
• Administered intravenously, preferably as a continuous infusion using a perfusor for rapid dose adjustments.
• Dosage: See Table 4.4 for high thromboembolic risk.

Patients on Coumarin Therapy

• Preoperative Management:
• If possible, discontinue coumarin therapy approximately 10 days before surgery.
• Adjust the Quick value to 50% (INR 1.5).
• Switch to perioperative administration of low-molecular-weight heparin (NMH) for thrombosis risk management.
• If Anticoagulation Cannot Be Interrupted:
• Replace coumarin therapy with intravenous heparin (UFH) therapy (refer to Table 4.5 for dosage).
• Increase Quick value through Konakion (Vitamin K) administration.
• In case of emergency, provide FFP (Fresh Frozen Plasma) and PPSB (Prothrombin Complex Concentrate) until drainage no longer shows blood, then resume coumarin therapy.

Patients on Antiplatelet Therapy

• Management:
• No additional perioperative heparin therapy is required.
• Discontinue aspirin (ASS) or clopidogrel 7-10 days before surgery.
• Start low-molecular-weight heparin 1-2 days postoperatively, once drainage is not actively bleeding.
• Resuming aspirin or clopidogrel should only occur 1 week postoperatively unless undergoing vascular procedures.