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Tuesday, November 3, 2020

Anticoagulants Drugs, Types, action, dosage



  • Heparin. 
  • Low molecular weight (LMW) heparin e.g dalteparin, enoxaparin, tinzaparin, fondaparinux. 
  • Heparinoids e.g danaparoid.
  • Direct thrombin inhibitors, e.g lepirudin, dabigatran, rivaroxaban. 
  • Anticoagulant prostanoids, e.g epoprostenol, alprostadil. 
  • Sodium citrate. 
  • Warfarin. 
Modes of action

  • Heparin potentiates naturally occurring antithrombin, reduces platelet adhesion to injured vessels, and promotes in vitro aggregation. 
  • LMW heparin appears to influence factor Xa activity specifically, simpler pharmacokinetics allows a smaller dose to be effective.
  • Heparanoids are similar to heparin, with 10-20% risk of cross-reactivity. Use is mainly restricted to treating heparin-induced thrombocytopenia syndrome (HITS) and DVT prophylaxis. No antidote is available. 
  • Lepirudin is a recombinant form of hirudin that form an irreversible complex with thrombin. It is unrelated to heparin so can be used to treat HITS. Antibody formation occurs 40% of patients treated with lepirudin >6 days. Half-life is long and there is no antidote. 
  • Dabigatran and rivaroxaban are being developed for oral thromboprophylaxis or treatment of thromboembolism without monitoring. There is no antidote, but half-lives are short. 
  • Prostanoids affect the balance between native TXA2 and PGI2.
  • Sodium citrate chelates ionised calcium. 
  • Warfarin produces a controlled deficiency of vitamin K dependent coagulation factors ( II, VII, IX and X). Effects develop in 48-72 h. 

  • Maintenance of an extracorporeal circulation. 
  • Prevention or treatment of thromboembolism. 

  • IV (heparin, heparinoids, prostanoids, sodium citrate )
  • SC (heparin )
  • PO (warfarin)
Side effects 

  • Bleeding 
  • Hypotension 
  • Heparin-induced thrombocytopenia 
  • Hypocalcaemia hypernatraemia ( sodium citrate )

  • Alprostadil is less potent than epoprostenol. As it is metabolised in the lungs, systemic vasodilatation effects are usually minimal. 
  • For extracorporeal use, citrate have advantages over heparin as it has no antiplatelet activity and is readily haemofiltered.


Unfractionated heparin 

Dose is titrated to produce an APTT of 1.5-3 times control. This usually requires 500 - 2000 IU/h with initial loading dose of 3000 - 5000 IU. 

Low molecular weight heparin 

For DVT prophylaxis, give 2500 - 5000 IU dalteparin or 20-40 mg enoxaparin sc daily
For anticoagulation for an extracorporeal circuit, an IV bolus of 35IU/kg dalteparin or 0.25mg/kg enoxaparin is followed by an infusion of 13 IU/kg dalteparin or 0.1 mg/kg enoxaparin. Adjust dose to maintain anti-factor  Xa activity at 0.5-1 IU /mL (or 0.2 - 0.4 IU/mL if high risk of hemorrhage ). 
For DVT pulmonary embolism, give 200 IU /kg dalteparin or 1.5 mg/kg enoxaparin SC daily 


Caution in patients with renal insufficiency. 
For DVT, prophylaxis gives 750 anti -Xa units danaparoid SC bd. 
For DVT or pulmonary embolism with history of HITS, give a loading dose of 2500 anti-Xa units danaparoid IVIV, them infusion of 400 U/h for 2h, 300U/h 2h, then maintenance of 200 U/h for five days. Target a therapeutic anti-Xa level during the infusion of 0.5-0.7 anti-Xa units/mL. 
For anticoagulation for an extracorporeal circuit, loading dose of 3,500 anti-Xa units danaparoid IV is followed by continuous infusion of 100 anti-Xa units/h. 

Direct thrombin inhibitors 

Lepirudin 0.1-0.4 mg/kg bolus followed by 0.1 -0.15 mg/kg/h infusion. Caution in patients with renal insufficiency. 

Anticoagulant prostaglandins

Usual dose range is 2.5 -10ng/kg/min. If used for an extracorporeal circulation, infusion should be started 30min prior to commencement. 

Sodium citrate 

Infused at 5mmol/L of extracorporeal blood flow. Monitor Ca2+ (ideally ionised levels and treat as needed ). 


Start at 10/day orally for two days, then 1-6mg/day according to INR. For DVT prophylaxis, pulmonary embolus, mitral stenosis, atrial fibrillation, and tissue value replacement, maintain INR between 2-3, For recurrent DVT or pulmonary embolus, and mechanical valve replacement, the INR should be kept between 3-4.5.

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