A sulphated mucopolysaccharide of variable chain lengths

Extracted from porcine intestine mucosa & bovine lung

MW: 3000 – 30,000 Da

pH: strongly acidic (high sulphate content) ∴negatively charged

Solubility: hydrophilic & poorly lipid soluble. Cannot cross lipid barriers 2° high MW & poor lipid solubility


  1. Tx thrombi
  2. Prevent thrombi
  3. Extracorporeal circuits
  4. Prevents thrombus formation in vascular procedures


Clear solution for injection. IU/mL


  • Commercial heparin is a family of molecules of different molecular weights
  • ∴ level of heparin doesn’t correlate to anticoag activity
  • Expressed as units of activity
  • 1 unit = volume of heparin that will prevent 1mL of sheep’s blood from clotting for 1hr

Prophylaxis: 5000 IU (SC) BD

Therapeutic: 5000IU IV load → 10IU/kg/hr to an APTT 1.5 – 2.5 x normal (S/C) = 1mg/kg


IV/SC → cannot be given IM 2° high risk haematoma at site

Onset / DoA


Time to normal haemostasis after cessation


1 min

4 – 6hr


45 min

4 – 6hr

MoA (mechanism)

  1. Impairs coagulation
    • Alone has no anticoagulant activity
    • Requires AT III as cofactor
    • Binds AT III → conformational ∆ → exposes active site & ↑its rate of reaction by x 1000
    • AT III
      • Inhibits all intrinsic pathway enzymes (XIa, XIIa, IXa)
      • Inhibits common pathway factors (IIa, Xa)
      • You need a long stretch of heparin to inhibit THROMBIN
      • UFH = long ∴ Xa thrombin inhibition is 1 : 1
      • You only need short stretch to inhibit Xa

2. Inhibits platelet function → strong platelet inhibition

3. ↓ TAG levels → released lipid hydrolysing enzyme

4. ↑ vascular permeability


  1. Impairs coagulation
  2. Inhibits platelet aggregation by Fibrin
  3. ↑plasma FFAs
  4. Osteoporosis & aldosterone suppression (long T)



High MW/low lipid solubility

Poor oral absorption



High PPB

→ Binds plasma proteins, endothelial cells, vascular wall proteins

→ Accounts for large interpatient variability

VD 40 – 100mL/kg


∴ anticoagulant of choice in pregnancy


Heparinases in liver

RES & kidneys


Metabolites renally excreted

Kinetics not affected by renal impairment

↓elimination with hypothermia

Adverse Effects

  • HMMRG → ↑ risk
  • ↓platelets → non immune (type 1): 0 – 4 days → platelet count recovers spontaneously

→ Immune (type 2 thrombocytopenia = HIT/HITT): 4 – 14 days → IgG mediated → heparin forms complex with platelet factor 4 → causes platelet aggregation & thrombus

  • Osteoporosis (↑ clast activity = bone reabsorption → osteoporosis)
  • Alopecia
  • Resistance’ = requires AT III for anticoagulant activity. Tx with FFP


Elevated temp & ↓BP (with high doses given for CPB)

Platelets (thombocytopaenia)

Anaphylaxis & alopecia

Ruins bones (osteoporosis)

Impaired mineralocorticoid production (hypoaldosteronism)

Noci (pain @ injection site)


Activated partial thromboplastin time (APTT)

  • APTT used to measure Intrinsic Pathway Factors (VIII, IX , XI, XII)
  • Can also be used for X, V, II but PT assays more commonly used
  • Blood sample is exposed to negatively charged activator + Ca2+
  • Inhibition of F IX activity by heparin prolongs APTT
  • Once they add Ca2+ to sample → measure time for clot to form → normally 28 – 35 secs
  • Heparin → ↑APTT x 1.5 – 2.5 for therapeutic effect
  • Not required for prophylactic dose because doesn’t elevate APTT


Activated clotting time

  • Used for high dose heparin (CPB)
  • Point of care bedside test, must faster cf. APTT
  • Normal 90 – 150 sec
  • Blood incubated with Kaolin to activate intrinsic pathway
  • Seconds for whole blood to clot is measured

Affected by many things: warfarin, G IIb/IIIa inhibitors, hypothermia, (coag factor deficiencies, hypovolaemia, thrombocytopaenia)


Anti-Xa assays

  • Considered more accurate
  • Guidelines for the titration of heparin infusions using Anti-Xa levels
  • Particularly useful if you have a patient with a prolonged baseline APTT ie a lupus anticoagulant where the APTT will not be reflective of their heparin level


Protamine sulphate

1mg neutralises 100 units