ADD-ONS / MEDICATION / ANTICOAGULANT THERAPY

Unfractionated Heparin (UFH)

Created 03/02/2022, last revision 24/09/2023

  • native heparin is a polymer with a molecular weight ranging from 3 to 30 kDa; the average molecular weight of most commercial heparin preparations is in the range of 12 to 15 kDa
    • low molecular weight heparin (LMWH) ranges from 3 to 6 kDa
  • it functions as an anticoagulant, inhibiting the formation and extension of existing blood clots

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 ), thereby reducing the conversion of fibrinogen to fibrin
    • heparin augments AT III activity by about 1,000-fold
    • in the absence of AT III, heparin is ineffective and has no fibrinolytic activity
  • heparin additionally:
    • releases lipoprotein lipase from the endothelium (antilipidemic effect)
    • reduces platelet adhesion to the endothelium and the release of platelet-derived growth factor
    • has a mild antihistamine effect

Pharmacokinetics

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

Contraindications

  • active, uncontrolled bleeding
  • conditions with an increased risk of bleeding:
    • coagulopathy (incl. liver disease)
    • uncontrolled hypertension 
    • thrombocytopenia
    • intracranial hemorrhage
    • recent extensive ischemic stroke
    • infective endocarditis
    • aortic dissection
    • recent or active gastrointestinal bleeding
  • history of heparin-induced thrombocytopenia (HIT)
  • hypersensitivity to heparin or its components

Dosing and monitoring

Miniheparinization (prophylactic dose)

  • HEPARIN (1 amp=25000 IU/5ml) 5000 IU SC every 8-12 hours
    • no significant differences in the incidence of pulmonary embolism or deep vein thrombosis (DVT) were observed between the two types of heparin dosing (Reynolds, 2019)
    • in VTE prophylaxis, heparin has been replaced by LMWHs
      • occurrence of HIT is lower in patients receiving LMWH compared to UFH (Junqueira, 2017)

Full dose heparin (therapeutic dose)

  • check AT III, APTT, INR, and complete blood count (CBC) before initiating therapy
  • dilute HEPARIN (4 mL/20,000 IU) + 16 mL of NS (1mL = 1000 IU)
    • numerous concentrations are available and used; caution is required to avoid dosing errors
  • if starting with a bolus, administer 50-80 IU/kg IV bolus with a maximum dose of 5000 IU
  • the effects of heparin are measured via partial thromboplastin time (aPTT), which measures the time of plasma clotting; target aPTT range: 65-105 s  (1.5-2.5)
  • after IV bolus, proceed with continuous IV heparin infusion:
weight (kg) continuous infusion
(IU/h) 		mL/h
< 50 500 0.5
50-59 600 0,6
60-69 700 0.7
70-79 800 0.8
80-89 900 0.9
90-99 1000 1.0
100-109 1100 1.1
110-119 1200 1.2
> 119 1400 1.4
  • check aPTT 6 hours after starting the therapy
  • based on the results, adjust the dosage accordingly:
aPTT (s) stop infusion dose change  (IU/h) check aPTT
< 40 – + 250 IU/h + 0.25 mL/h in 6h
40-49 – + 150 IU/h + 0.15 mL/h in 6 h
50-59 – + 100 IU/h + 0.1 mL/h in 6 h
60-90 – – – – next day morning
91-100 – – 100 IU/h – 0.1 mL/h  in 6 h
101-120 – – 150 IU/h – 0.15 mL/h in 6 h
> 120 for 60 min – 250 IU/h – 0.25 mL/h  in 6 h
  • after achieving therapeutic levels, check APTT every 12h
  • avoid intramuscular injections during heparinization!

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 (following deep SC injections)
  • elevated liver aminotransferases
  • delayed transient alopecia
  • rebound hyperlipidemia upon heparin discontinuation
  • vasospastic reactions (including episodes of painful, ischemic, and cyanosed limbs)

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Unfractionated Heparin (UFH)
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