Epsilon Amino Caproic Acid (EACA)

Drug Name

Epsilon Aminocaproic Acid

  • Generic Name: Epsilon Amino Caproic Acid
  • Pronunciation: ep-si-lon a-mee-no ka-pro-ik a-sid
  • Common Brand Name (US): Amicar®

Drug Class

  • Pharmacologic Class: Antifibrinolytic Agent
  • Therapeutic Class: Hemostatic Agent
  • Chemical Class: Lysine Analog

Mechanism of Action (MOA)

EACA is a synthetic lysine analog. Its primary mechanism is the inhibition of fibrinolysis (the breakdown of blood clots). It achieves this through two key actions:

  1. Competitive Inhibition: It reversibly binds to the lysine-binding sites on plasminogen and plasmin molecules.
  2. Prevention of Binding: By occupying these sites, EACA prevents plasminogen from binding to fibrin, which is a necessary step for its activation to plasmin by tissue plasminogen activator (tPA). It also directly inhibits active plasmin from binding to and degrading fibrin.

In simple terms: EACA doesn't create clots; it protects existing clots from being dissolved by the body's own fibrinolytic system, thereby reducing bleeding.

Pharmacokinetics

  • Onset: IV onset is rapid, within minutes.
  • Distribution: Distributes widely into extracellular fluid, synovial fluid, and crosses the placenta. Minimal protein binding.
  • Metabolism: Undergoes minimal to no metabolism. It is excreted largely unchanged.
  • Excretion: Primarily renal via glomerular filtration. The half-life is approximately 2 hours in patients with normal renal function. Dose adjustment is mandatory in patients with renal impairment.

Dosing & Administration

  • Route: Intravenous (IV) and Oral (PO).
  • IV Dosing (for acute bleeding prevention):
    • Loading Dose: 100 mg/kg (up to a maximum of 5-10 grams) infused IV over 15-30 minutes.
    • Maintenance Infusion: 30 mg/kg/hour (or 1-2 g/hour) continued for the duration of the bleeding risk or until hemostasis is achieved.
  • Administration Note: The loading dose should be infused slowly to avoid hypotension. It is compatible with most common IV solutions.

Clinical Uses / Indications

EACA is used to prevent or treat bleeding in situations where fibrinolysis is a significant contributor. Common anesthesia and surgical indications include:

  • Cardiac Surgery: To reduce bleeding associated with cardiopulmonary bypass (CPB).
  • Major Orthopedic Surgery: Total hip and knee arthroplasty.
  • Liver Transplantation: To manage the complex coagulopathy associated with the procedure.
  • Trauma: As part of a massive transfusion protocol (MTP) for severe hemorrhage.
  • Obstetrics: For management of postpartum hemorrhage (e.g., placental abruption) or in patients with known bleeding disorders.
  • Other: Treatment of epistaxis (nosebleeds) and menorrhagia (heavy menstrual bleeding).

Contraindications

  • Absolute:
    • Active intravascular clotting (e.g., untreated Deep Vein Thrombosis [DVT], Pulmonary Embolism [PE]).
    • Hypersensitivity to EACA or any of its components.
  • Relative:
    • Disseminated Intravascular Coagulation (DIC) without clear evidence of dominant fibrinolysis.
    • Severe renal impairment (requires significant dose reduction).

Adverse Effects / Side Effects

  • Common:
    • Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain.
    • Cardiovascular: Hypotension (especially with rapid IV infusion), bradycardia.
    • Central Nervous System: Dizziness, headache, fatigue.
  • Serious (but less common):
    • Thrombosis: The most significant risk. Can lead to DVT, PE, myocardial infarction, or stroke.
    • Renal Failure: Can cause acute tubular necrosis due to precipitation of crystals in the renal tubules.
    • Myopathy/Rhabdomyolysis: Rare, but can be severe.
    • Visual Disturbances/Seizures: Very rare, reported with high plasma concentrations.

Drug Interactions

  • Pro-coagulants (e.g., Factor VIIa, Prothrombin Complex Concentrates): May have an additive effect, increasing the risk of thrombosis.
  • Hormonal Contraceptives: Increased risk of thrombotic events.
  • Thrombolytics (e.g., tPA, Streptokinase): Antagonistic effect. EACA will directly counteract the intended action of these drugs.

Monitoring Parameters

  • Clinical: Continuous monitoring for signs of ongoing bleeding and, critically, for new signs or symptoms of thrombosis (e.g., limb swelling, chest pain, shortness of breath, neurological changes).
  • Laboratory:
    • Thromboelastography (TEG) / Rotational Thromboelastometry (ROTEM): Monitor the LY30 or LY60 (percentage of clot lysis at 30/60 minutes) to assess fibrinolysis and guide therapy.
    • Renal Function: Baseline and daily BUN/Creatinine.
    • Urine Output: Monitor for adequate urine output to prevent renal precipitation.

Key Considerations for the Anesthesia Provider

  • Patient Selection is Crucial: Do not give to patients with active thrombosis or a high risk of thrombosis unless the benefit of hemorrhage control clearly outweighs the risk.
  • Renal Function is Paramount: Always assess baseline renal function and adjust the infusion dose accordingly.
  • Infuse Slowly: Rapid administration of the loading dose can cause significant hypotension.
  • Part of a Protocol: EACA is often a key component of a Massive Transfusion Protocol (MTP). Know your institution's protocol.
  • Know When to Stop: If a thrombotic event is suspected, the infusion must be stopped immediately.

Summary

Epsilon Amino Caproic Acid is a fundamental antifibrinolytic agent used to stabilize clots and reduce bleeding in high-risk surgical and trauma patients. While highly effective, its use requires careful patient selection, vigilant monitoring for thrombosis and renal dysfunction, and dose adjustment in renal impairment.

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