Antiinflammatory Effects of Argatroban Can Be Differentiated from Other Direct Thrombin Inhibitors. Experimental and Clinical Observations

Abstract

Direct thrombin inhibitors (DTIs) such as Argatroban, Angiomax and Lepirudin are used in the treatment of patients with heparin-induced thrombocytopenia (HIT). Some DTIs may be capable of additional effects such as vasomodulation, anti-inflammatory and cellular modulatory effects. Plasma samples collected pretreatment and 3 days after treatment from HIT patients administered Argatroban (n=10), Angiomax (n=7) or Lepirudin (n=14) were profiled for NO levels (Sievers, Boulder, CO) and markers of inflammation [myeloperoxidase (MPO), CD40 ligand (CD40L) and asymmetric dimethylarginine (ADMA)]. The control group consisted of 50 normal adult male and female volunteers. Levels of MPO and CD40L did not differ among the treatment groups at baseline, though they were higher relative to the control group. MPO and CD40L levels were not altered by treatment with Angiomax or Lepirudin. Moreover, ADMA levels were markedly increased. In the argatroban treated group, these levels were significantly decreased (p<0.05). However, when the NO levels were measured in platelets, an increase was noted in the argatroban group only. These studies suggest that argatroban is capable of upregulating intraplatelet NO levels which may be involved in the suppression of platelet activation in HIT. Together with this observation, and a down-regulation of various inflammatory markers, these observations are highly suggestive of the differential effects of argatroban in comparison to other DTIs.