ADD-ONS / MEDICATION / ANTICOAGULANT THERAPY

Unfractionated Heparin (UFH)

Created 03/02/2022, last revision 28/02/2022

  • 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, which inhibits thrombin and other factors (IX, X, XI, and XII ) leading to a reduced 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

  • 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, it 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

Dosage and monitoring

Miniheparinisation (prophylactic dose)
  • HEPARIN (1 amp=25000 IU/5ml) : 5000 units SC q8-12hr
    • no significant differences in the incidence of pulmonary embolism or deep vein thrombosis were observed between the two types of heparin dosing   (Reynolds, 2019)
  • monitoring of the effect is not necessary
  • in TEN prophylaxis, heparin is usually replaced by LMWH
    • occurrence of HIT is lower in patients receiving LMWH compared to UFH (Junqueira, 2017)
Full dose heparin (therapeutic dose)
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Adverse events

  • 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)
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