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Intraoperative Blood Products & Anticoagulants in the OT

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PART 1: PROCOAGULANT / HEMOSTATIC BLOOD PRODUCTS

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1. Fresh Frozen Plasma (FFP)

• Composition: Contains all coagulation factors (I, II, V, VII, VIII, IX, X, XI), fibrinogen, AT-III, proteins C and S. Prepared by rapid freezing of the plasma supernatant after centrifugation of whole blood - rapid freezing preserves the labile factors V and VIII.
• Indications:
  • Reversal of warfarin effect (immediate; vitamin K takes hours)
  • Correction of multiple coagulation factor deficiencies
  • Massive transfusion protocols - 1:1:1 ratio (FFP : platelets : PRBCs) used in trauma damage control resuscitation
  • Coagulopathy of liver disease
  • Dilutional coagulopathy after large-volume PRBCs
• Dose: Typically 10-15 mL/kg; 1 unit raises factor levels by ~2-3%
• Key monitoring: INR/PT, aPTT
• Risks: Transfusion-related acute lung injury (TRALI), TACO, allergic reactions, ABO incompatibility, infection
• Source: Morgan and Mikhail's Clinical Anesthesiology, 7e; Barash Clinical Anesthesia, 9e; Current Surgical Therapy, 14e

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2. Cryoprecipitate

• Composition: Prepared by slow thawing of FFP - yields a gelatinous precipitate containing concentrated factor VIII, factor XIII, von Willebrand factor (vWF), and fibrinogen.
• Indications:
  • Hypofibrinogenemia (fibrinogen <100-150 mg/dL)
  • Hemophilia A (factor VIII deficiency)
  • von Willebrand disease
  • Uremic bleeding
  • Major surgical hemorrhage with depleted fibrinogen
• Dose: 1 unit per 5-10 kg body weight; raises fibrinogen by ~50 mg/dL per 10 units
• Source: Morgan and Mikhail's, 7e; Barash, 9e

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3. Platelets

• Storage: 20°C-24°C for up to 5 days; ~50-70 mL plasma per unit
• Indications:
  • Thrombocytopenia with bleeding (threshold: count <50,000 for most surgery; <100,000 for neurosurgery)
  • Platelet dysfunction (e.g., post-cardiopulmonary bypass, uremia, antiplatelet drugs)
  • Massive transfusion (1:1:1 protocol)
• Dose: 1 apheresis unit raises platelet count by 30,000-60,000/µL
• Neurosurgery note: Patients having neurosurgical procedures should have platelet count >100,000 preoperatively - intraoperative or postoperative bleeding has a significantly adverse impact on outcome. - Barash, 9e
• Source: Morgan and Mikhail's, 7e; Barash, 9e

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4. Prothrombin Complex Concentrate (PCC)

• Types:
  • 3-factor PCC - contains factors II, IX, X
  • 4-factor PCC - contains factors II, VII, IX, X + proteins C and S
• Indications:
  • Urgent reversal of warfarin/vitamin K antagonists (preferred over FFP for speed and volume)
  • Life-threatening hemorrhage
  • Perioperative coagulopathy when benefit outweighs thrombosis risk
• Advantage over FFP: Small volume (20-40 mL vs. 250 mL), no cross-matching, immediate availability
• Source: Morgan and Mikhail's, 7e; Fischer's Mastery of Surgery, 8e

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5. Recombinant Factor VIIa (rFVIIa, NovoSeven)

• Mechanism: Activates the extrinsic pathway by forming a complex with tissue factor at the site of vascular injury, generating a large thrombin burst. Acts at supraphysiologic doses even without tissue factor.
• Indications (OT):
  • Hemophilia A or B with inhibitors
  • Uncontrolled surgical hemorrhage refractory to conventional therapy
  • Major liver surgery, trauma, necrotizing enterocolitis with massive bleeding
• Caution: Risk of thromboembolism; use only when benefit outweighs risk
• Source: Morgan and Mikhail's, 7e; Fischer's Mastery of Surgery, 8e

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6. Fibrinogen Concentrate

• Mechanism: Directly supplements fibrinogen (Factor I), the substrate for thrombin to form fibrin clot
• Indications: Congenital afibrinogenemia, acquired hypofibrinogenemia in massive hemorrhage
• Advantage over cryoprecipitate: Standardized dosing, no blood group compatibility required, smaller volume, faster administration
• Source: Miller's Anesthesia, 10e; Fischer's Mastery of Surgery, 8e

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7. Packed Red Blood Cells (PRBCs)

• Hematocrit: ~70% per unit; volume ~250-350 mL
• Trigger: Hb <7 g/dL in most patients; Hb <8-10 g/dL in cardiac disease or high-risk surgery
• Intraoperative use: Restore oxygen-carrying capacity; threshold must balance against transfusion risks
• Storage anticoagulant: CPDA-1 (citrate as anticoagulant, phosphate as buffer, dextrose, adenosine) - shelf life 35 days; AS-1/AS-3 extend to 6 weeks
• Massive transfusion: 1:1:1 with FFP and platelets
• Source: Morgan and Mikhail's, 7e

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PART 2: ANTICOAGULANTS USED INTRAOPERATIVELY

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1. Unfractionated Heparin (UFH)

• Mechanism: Activates antithrombin III (AT-III), which then inhibits thrombin (IIa) and factor Xa (and to a lesser extent IXa, XIa, XIIa). Prevents fibrin formation.
• Primary intraoperative use: Standard anticoagulant for cardiopulmonary bypass (CPB) in cardiac surgery; also used in vascular surgery (e.g., carotid endarterectomy, peripheral arterial bypass, AV fistula creation)
• Dose for CPB: 300-400 units/kg IV; target activated clotting time (ACT) >480 sec for CPB, >200 sec for vascular procedures
• Monitoring: ACT (intraoperatively); aPTT (ward)
• Reversal: Protamine sulfate (1 mg per 100 units of heparin administered); given at end of CPB
• Complication: Heparin-Induced Thrombocytopenia with Thrombosis (HITT) - immune complex causes paradoxical thrombosis; must switch to direct thrombin inhibitors
• Source: Current Surgical Therapy, 14e; Barash, 9e

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2. Low-Molecular-Weight Heparin (LMWH) - e.g., Enoxaparin, Dalteparin

• Mechanism: Consists of smaller, more uniform molecules than UFH; inhibits factor Xa only (not thrombin/IIa) - acts higher up in the cascade
• Intraoperative relevance: Primarily a preoperative/postoperative anticoagulant; must be stopped before surgery (last dose 12-24 hrs prior). Not typically used during active surgery.
• Reversal: Partial reversal with protamine (~60% efficacy)
• Source: Current Surgical Therapy, 14e

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3. Bivalirudin (Angiomax)

• Class: Direct thrombin inhibitor (DTI)
• Mechanism: Directly and reversibly binds to the active site of thrombin, inhibiting thrombin-mediated clot formation. Does NOT require AT-III.
• Key intraoperative indications:
  • Patients with HIT or HITT who require cardiac surgery (on-pump or off-pump) - >90% efficacy, acceptable bleeding outcomes
  • Alternative to heparin in HIT patients undergoing vascular procedures
• Monitoring: ACT or aPTT
• Reversal: No reversal agent - relies on renal clearance (half-life ~25 min)
• Source: Current Surgical Therapy, 14e; Barash, 9e

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4. Argatroban

• Class: Direct thrombin inhibitor
• Mechanism: Synthetic, reversible competitive inhibitor of thrombin; hepatically cleared (preferred over bivalirudin in renal impairment)
• Intraoperative use: FDA-approved for treatment of HITT; used for anticoagulation during cardiac/vascular procedures in HIT patients
• Monitoring: aPTT or ACT
• No reversal agent
• Source: Current Surgical Therapy, 14e; Barash, 9e

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5. Warfarin (Perioperative Context)

• Mechanism: Vitamin K antagonist - depletes factors II, VII, IX, X and proteins C and S
• Intraoperative concern: Must be stopped preoperatively (INR must normalize). If urgent surgery needed while on warfarin, reverse with FFP (immediate) or 4-factor PCC ± vitamin K
• Bridging: Patients with mechanical valves/AF on warfarin may need heparin bridging perioperatively
• Source: Current Surgical Therapy, 14e

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6. Direct Oral Anticoagulants (DOACs)

• Intraoperative relevance: Must be stopped before elective surgery (24-48 hrs, longer for renal impairment). If emergency surgery needed with active DOAC on board, specific reversal agents should be available.
• Note: DOACs are contraindicated in patients with mechanical heart valve prostheses - warfarin remains the agent of choice in this population
• Source: Current Surgical Therapy, 14e

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PART 3: ANTIFIBRINOLYTICS (Intraoperative Hemostatic Adjuncts)

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1. Tranexamic Acid (TXA)

• Mechanism: Reversibly binds to plasminogen at its lysine-binding site, blocking plasminogen-fibrin interaction and inhibiting plasmin's proteolytic activity. Prevents clot lysis (fibrinolysis).
• Indications:
  • Cardiac surgery with CPB (reduces post-bypass bleeding and transfusion)
  • Orthopedic surgery (TKA, THA, spine surgery) - most evidence
  • Trauma/massive hemorrhage (military and civilian protocols)
  • Liver surgery
• Dose (orthopedic): 10-15 mg/kg IV before incision + 1 mg/kg/h infusion during surgery; OR topical 1-3 g
• Evidence: Multiple meta-analyses confirm significant reductions in intraoperative/postoperative blood loss and transfusion rates in spine, TKA, THA, and cardiac surgery
• Risk: Theoretical thromboembolic risk; studies have not shown significant increase in VTE at standard doses
• Source: Miller's Anesthesia, 10e; Barash, 9e; Campbell Walsh Wein Urology

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2. Epsilon-Aminocaproic Acid (EACA, Amicar)

• Mechanism: Same as TXA - binds plasminogen, inhibits fibrinolysis
• Indications: Cardiac surgery (CPB), spine surgery, hemophilia (adjunct)
• Dose: Loading 100-150 mg/kg or 5 g IV, then 10-15 mg/kg/h infusion; for THA/TKA: 5-10 g fixed dose
• Compared to TXA: Slightly less potent; less evidence in orthopedic surgery; similar cardiac surgery efficacy
• Source: Miller's Anesthesia, 10e; Barash, 9e

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3. Aprotinin (Trasylol) - Serine Protease Inhibitor

• Mechanism: Broad protease inhibitor - inhibits plasmin, kallikrein, and other serine proteases; also preserves platelet function
• Historic use: Was widely used in cardiac surgery but withdrawn in many countries due to increased renal failure and mortality risk (BART trial)
• Current status: Available in some countries with restricted use

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PART 4: SPECIAL SITUATIONS IN THE OT

Massive Transfusion Protocol (MTP)

• Ratio: 1:1:1 (PRBCs : FFP : platelets) - termed damage control resuscitation
• Used in trauma, ruptured aortic aneurysm, massive obstetric hemorrhage
• Based on military experience and civilian trauma studies
• Often combined with TXA (CRASH-2 trial evidence)
• Source: Morgan and Mikhail's, 7e; Fischer's Mastery of Surgery, 8e

Cardiac Surgery with CPB

• Standard protocol: UFH 300-400 units/kg → target ACT >480 sec → surgery → protamine reversal
• HIT patients: Bivalirudin or argatroban instead of heparin
• Blood conservation: Antifibrinolytics (TXA/EACA) + acute normovolemic hemodilution (ANH) + cell saver
• Post-CPB coagulopathy: FFP, platelets, cryoprecipitate as guided by TEG/ROTEM or point-of-care testing

Patient Refusing Transfusion (e.g., Jehovah's Witnesses)

• Cell salvage (autologous blood recovery)
• Erythropoietin preoperatively
• Iron supplementation
• Factor concentrates: PCC, fibrinogen concentrate, factor VIII/IX, rFVIIa, cryoprecipitate (if acceptable to patient)

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Quick Reference Summary Table

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• Morgan and Mikhail's Clinical Anesthesiology, 7e - Chapters on blood transfusion and procoagulant therapy
• Barash, Cullen, and Stoelting's Clinical Anesthesia, 9e - Transfusion therapy; Blood conservation in cardiac surgery
• Current Surgical Therapy, 14e - Heparin, warfarin, bivalirudin, direct oral anticoagulants
• Miller's Anesthesia, 10e - Antifibrinolytic drugs; perioperative blood management
• Fischer's Mastery of Surgery, 8e - Massive transfusion protocols; patients refusing transfusion