ADD-ONS / MEDICATION / ANTICOAGULANT THERAPY

Unfractionated Heparin (UFH)

Created 03/02/2022, last revision 21/01/2023

• native heparin is a polymer with a molecular weight ranging from 3 to 30 kDa, although the average molecular weight of most commercial heparin preparations is in the range of 12 to 15 kDa
  • while low molecular weight heparin ranges from 3 to 6 kDa
• it acts as an anticoagulant, preventing the formation of clots and extension of existing clots within the blood

Pharmacodynamics

• heparin acts as an anticoagulant by activating antithrombin III (AT III)
  • AT III is an α2-globulin synthesized in the liver
  • it inhibits thrombin and other factors (IX, X, XI, and XII ), which reduces the conversion of fibrinogen to fibrin
    
  • heparin augments AT III activity by about 1,000 times
    
  • heparin has no effect in the absence of AT III and has no fibrinolytic activity
• heparin further:
  • releases lipoprotein lipase from the endothelium, which determines its antilipidemic effect
  • reduces platelet adhesion to endothelium and release of the platelet-derived growth factor
    
  • has a mild antihistamine effect

Pharmacokinetics

• the onset of the effect:
  • IV – immediate
  • SC – within 20-30 min
• the biological half-life is approximately 1-2 h (longer at higher doses); therefore, continuous infusion is preferable to intermittent IV administration
• after SC administration, peak plasma levels are reached in 2-4 h
• heparin binds to plasma proteins, some of which (particularly in inflammatory or tumor diseases) neutralize its anticoagulant activity
• biotransformation: liver and RES
• heparin is excreted in the urine and is not dialyzable
• heparin does not cross the placental barrier and does not pass into breast milk

Contraindications

• common contraindication like increased risk of bleeding (especially in people with uncontrolled blood pressure, liver disease, and stroke)
• HIT in patient´s personal history

Dosing and monitoring

• bleeding complications →  neutralizing the effect of heparin
• heparin-induced thrombocytopenia (HIT)
• osteoporosis (long-term, high-dose treatment)
• allergic reactions
• hyperkalemia, hyperaldosteronism
• injection site ulcer (after deep SC injection)
• increased liver aminotransferase
• delayed transient alopecia
• rebound hyperlipemia on discontinuation of heparin
• vasospastic reactions (including episodes of painful, ischemic, and cyanosed limbs)