Argatroban

Argatroban, a synthetic hirudin analogue (L-arginine derivative), is a direct thrombin inhibitor that reversibly binds to thrombin. The anticoagulant has been approved since 2005 for anticoagulation in adult patients with heparin-induced thrombocytopenia type II (HIT II) who require parenteral antithrombotic therapy

The anticoagulation effect of argatroban is independent of antithrombin III, inhibiting the formation of fibrin, activation of coagulation factors V, VIII and XIII, activation of protein C and activation of platelet aggregation. Argatroban is bound to 54% of human serum proteins. Argatroban is able to inhibit the action of both freely circulating and fibrin-bound thrombin. It does not interact with heparin-induced antibodies. Argatroban is mainly excreted via the feces, probably via biliary secretion.

Anticoagulation in adult patients with heparin-induced thrombocytopenia type II (HIT-II) who require parenteral antithrombotic therapy The diagnosis should be confirmed by the HIPAA ("heparin induced platelet activation assay") or an appropriate test (Rice L 2005).

Individual reports show positive effects in rhematoid vasculitis (Kawakami T et al. 2008) and zoster-induced pain (Fujii K et al. 2001).

Frequently: vascular diseases (e.g. bleeding), nausea, skin diseases (e.g. purpura).

Occasionally: heart diseases (e.g. tachycardia, hypertension), liver and bile diseases, skeletal muscle and bone diseases, connective tissue diseases, urinary tract and kidney diseases, general complaints (e.g. pyrexia), diseases of the gastrointestinal tract, diseases of the respiratory tract, chest and mediastinum, skin diseases (e.g. urticaria, alopecia).

Argatra®

Treatment with Argatroban should be carried out under the supervision of a doctor experienced in treating coagulation disorders, preferably in an intensive care unit. It should be carried out under close monitoring of the activated partial thromboplastin time (aPTT) until the aPTT is within the target range. Thereafter, monitoring of the aPTT should be performed once a day. The argatrobank concentrations in plasma correlate with the anticoagulation effect measured by the aPTT value.

There is no specific antidote against Argatroban.

1. Fujii K et al (2001) A specific thrombin inhibitor, argatroban, alleviates herpes zoster-associated pain. J Dermatol 28:200-207.
2. Greinacher T (2008) Thrombocytopenia and platelet dysfunction. In: Thomas L (Ed) Laboratory and diagnosis. Th-Books Publishing Company Ltd, Frankfurt/Main p. 918
3. Gupta S et al (2008) Heparin induced thrombocytopenia. J Assoc Physicians India 56:622-627.
4. Kawakami T et al (2008) Therapeutic effect of argatroban on rheumatoid vasculitis with antiphosphatidylserine-prothrombin complex antibody. Arch Dermatol 144:1075-1076.
5. Lewis BE et al (2003) Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med 163: 1849-1856

6. Rice L (2005) Evolving management strategies for heparin-induced thrombocytopenia. Semin Hematol 42 (3 Suppl 3):15-S21