Hirudin

Chemical

Natural peptide of salivary glands of leeches

First anticoagulant

LEPIRUDIN is the recombinant version, exactly the same except for 1 amino-acid sub

Use

  1. Anticoagulation in patients with HITS
  2. DIC

Note: not available in Australia

Presentation

50mg vial

Dose

0.4mg/kg (IV) over 20 secs

Then 0.15mg/kg/hr (IV) for 2 – 10 days

Route

IV/SC

Onset / DoA

Onset = immediate

t ½ B = 10 mins

MoA

Thrombin acts to:

  • Fibrinogen → Fibrin monomers
  • Activate XIII → XIIIa which stabilises fibrin polymers
  • XI → Xia
  • VIII → VIIIa
  • V → Va
  • Platelet agonist+++
  • Intact endothelium Thrombomodulin binds Thrombin → activator PrC = anticoagulant effect

Thrombin has 3 binding sites

  1. ACTIVE Catalytic site
  2. FIBRIN binding site
  3. HEPARIN binding site

Hirudin is a BIVALENT thrombin inhibitor

Binds both Fibrin BS & Catalytic Site

Binds irreversibly

Antagonises effects of thrombin

Irreversible Thrombin Inhibitor → inhibits free & clot bound thrombin

PK

A

IV & SC = 100% bioavailability

Rapid distribution to extracellular space

D

VD 12 – 32L

∴ confined to extracellular space

Doesn’t cross BBB/breast milk

M

90% metabolism through renal clearance

35% unchanged

E

Renal excretion

Peak APTT 10 mins after bolus & 6hrs after starting infusion

Adverse Effects

  • Bleeding
  • Ab development → comment
  • Allergic reaction; eczema; rashes

Monitoring

APTT & PT times prolonged (due to thrombin inhibition) → requires monitoring

Reversal

No specific antidote

Desmopressin partially reverses

Can eliminate with dialysis