LMWH

Chemical

Heparin is a sulphated mono-polysaccharide

LMWH extracted from UFH by chemical depolymerisation

  • MW – 3000 – 30,000 Da
  • pH – strongly acidic (high sulphate content) ∴ negatively charged

Solubility – hydrophilic & poorly soluble

Use

  1. Tx thrombi
  2. Prevent thrombi

Presentation

Clear solution for injection

Dose

  • Dalteparin in anti-Xa units
  • Enoxaparin in mg

Prophylaxis: 40mg (Subcut) OD

Therapeutic: 1mg/kg/day (Subcut)

Route

SC

Onset / DoA

Peak ~4hrs → time to normal haemostasis following discontinuation >12hrs

MoA

Inhibits coagulation

  • Binds AT III –> potentiates AT activity

(by itself has no anticoagulant activity)

  • ↑AT inhibition of Xa (only inhibits Xa)
  • ∴ inhibits conversion of Prothrombin → Thrombin
  • Short molecule ∴ not long enough to affect thrombin itself LIKE UFH

→ Small doses can inhibit thrombosis (prevention) by inactivating Xa & stopping PROTHROMBIN → THROMBIN

→ Larger doses inhibit further coagulation once a clot has developed (IX)

→ Also prevents formation of stable clot by inhibiting the activation of Fibrin Stablising Factor

Moderate inhibition of platelets

PD

  1. Impairs coagulation
  2. Platelet dysfunction

PK

A

100% bioavailability (Subcut) because much lower PPB cf. UFH

D

Much more predictable & reproducible response

M

Desulfation +/- depolymerisation in liver

E

Majority of dose renally cleared as active/inactive fragments

Needs dose adjustment in renal failure

Adverse Effects

  • Haemorrhage
  • Elevated temp & ↓BP (with high doses given for CPB)
  • Platelets (thombocytopaenia)
  • Anaphylaxis & alopecia
  • Ruins bones (osteoporosis)
  • Impaired mineralocorticoid production (hypoaldosteronism)
  • Noci (pain @ injection site)
  • Avoid LMWH in HITS patients (UFH) because cross reactivity with LMWH Ab’s can occur

Monitoring

  • Anti – Xa – level
  • Due to predictable anticoagulant response, monitoring is not usually required, however…monitoring is suggested in pregnancy, extremes of weight, renal dysfunction or patients with significant bleeding risk

Reversal

Protamine

  • Does not bind as well + smaller fractions
  • ∴ unpredictable reversibility up to 60% of dose

And anti-Xa activity can recur after protamine dose due to addit release from S/C depot