21B19: Exam Report

Outline the process of fibrinolysis (40% marks). Write short notes on the indications, mechanism of action, pharmacokinetics and side effects of tranexamic acid (60% marks)

30% of candidates passed this question.

The relative allocation of marks and thus time to be spent on each component was delineated by the relative percentages in the question. The first part of the question required a step-by-step outline of the fibrinolytic pathway with mention of the regulatory processes. Tranexamic acid is an important drug in the practice of intensive care and the question provided the headings under which to answer the question. The detail surrounding the keys aspects of this drug with respect to its use in critical care were often vague and underappreciated.

Q1iv / 15B19: Outline the process of fibrinolysis (40% marks). Write short notes on the indications, mechanism of action, pharmacokinetics and side effects of tranexamic acid (60% marks)


Fibrinolysis is a physiological mechanism in which the fibrin within blood clots is slowly dissolved.
  • Plasminogen is a β-globulin (proenzyme synthesised by liver)
  • Plasminogen becomes interwoven into fibrin clot as it is formed
  • Plasminogen \( \underrightarrow {\text{tPA (expressed by endothelial cells) }} \) plasmin (serum protease)
    • Keeps endothelial cell surface free of fibrin deposits → small vessels patent
  • Fibrin is cleaved by plasmin → fibrin degradation products (FDP)
    • D-dimer (a FDP): cleavage product of cross-linked fibrin
  • Much slower process than coagulation
  • Time lag between clot formation & clot dissolution allows healing to take place
  This conversion is initiated by
  • Extrinsic activation (from the tissues) → by endothelial tPA (enhanced by local thrombin production), which circulates and activates ONLY fibrin-bound plasminogen (ie localised to the clot)
  • Intrinsic activation (from the vessel wall) → by CF XIIa, kalikrein
  • Urokinase → produced by monocytes, macrophages, urinary epithelium

Regulatory processes

Mechanism of Action

Increases Fibrinolysis

Decreases Fibrinolysis

Mechanism of Action

Effect on plasmin

Increases Fibrinolysis

Decreases Fibrinolysis

Plasmin inactivation:

  • Α2 macroglobulin
  • Α2 antiplasmin

Mechanism of Action

Effect on plasminogen

Increases Fibrinolysis

Facilitate the conversion of plasminogen to plasmin

  • Streptokinase
  • Urokinase
  • Tissue plasminogen activator
  • Alteplase

Decreases Fibrinolysis

Competitively inhibits the conversion of plasminogen to plasmin

  • Tranexamic acid

Regulation of Fibrinolysis

  • Plasmin Activator Inhibitor (PAI) 1 & 2: produced by vascular endothelium and inhibits tissue plasminogen activator and urokinase
  • Protein C inactivates plasmin activator inhibitor, thrombin activatable fibrinolysis inhibitor
  • Thrombomodulin (expressed on intact endothelium): binds thrombin and subsequently activates protein C
  • Thrombin activatable fibrinolysis inhibitor: produced by liver & cleaves plasmin binding sites on fibrin → ↓degradation
  • α2 antiplasmin: produced by liver, inhibits circulating plasmin, not fibrin bound plasmin

Tranexamic acid

Tranexamic Acid


A synthetic analogue of LYSINE

WHO’s list of essential medicines

(the most effective & safe medicines needed in a health system)


  1. Cardiac sx (↓peri-op bleeding)
  2. Reverse thrombolytic therapy
  3. Menorrhagia
  4. Dental bleeding
  5. Epistaxis
  6. Haemoptysis
  7. Haemorrhagic shock (Trauma, Obs + surgical haemorrhage)
  8. DIC


Tablets 500mg


  • 5000mg/50mL
  • 1000mg/10mL
  • 500mg/5mL


Menorrhagia: PO 1g QID

IV 20mg/kg over 5 mins

Trauma/haemorrhage: IV 1g over 10min (IV) → 1g IV over 8hrs

Epistaxis → topical

Mouthwash → 10mL 5%

Dose adjust in ↓renal impairment




5 – 15 mins → DoA 3hrs

MoA (mechanism)

  • Binds plasminogen lysine binding sites (REVERSIBLE)
  • Competitively inhibits activation of plasminogen → plasmin
  • ∴stops fibrinolysis
  • 10 x stronger than aminocaproeic acid
  • At v. high doses inhibits PLASMIN





OBA 34%


3% PPB because binds almost exclusively to plasminogen





95% unchanged

t ½ 2 – 11hrs

Adverse Effects

Ocular – vision ∆


Renal impairment

Pulmonary Hypertension

Hypotension with rapid administration

GI disturbance (PO) → N&V, diarrhoea, GORD

Intravascular thrombosis (largely theoretical); no consistent data that shows increased risk of thrombosis with its use

  • Discovered by Utako Okamoto in 1950s 🇯🇵 … who was looking for a drug to treat PPH
  • She could not persuade Kobe obstetricians to use it… however eventually made its way to the WHO essential medicine list!

Author: Novia Tan