Antibody Formation

Because hirudin is a protein obtained from a nonhuman species, lepirudin can induce antibody formation in humans. Antibodies are induced by both iv therapeutic-dose and sc prophylactic-dose use (Greinacher et al., 2003a). Antihirudin antibodies have been detected in 44-74% of patients treated with lepirudin (Huhle et al., 1998; Song et al., 1999; Eichler et al., 2000). Of 196 HIT patients treated with lepirudin for 5 or more days, 44% developed antihirudin antibodies of the IgG class (Eichler et al., 2000). Reexposed patients developed antibodies in about 70% of cases (Lubenow et al., 2005). These antibodies were not associated with an increase in thrombin-antithrombin (TAT) complexes (Fig. 6). Antibody formation occurred as early as day 4 and peaked at days 8-9 (Eichler et al., 2000).

Antilepirudin antibodies can extend the half-life of lepirudin (Liebe et al., 2002), most likely by reduced renal filtration of lepirudin-antilepirudin complexes

FIGURE 6 TAT complex concentrations in relation to antihirudin antibody formation. TAT complex concentrations did not differ between antihirudin antibody-positive (*, solid lines) and antihirudin antibody-negative (O, dotted lines) patients (median and 25% and 75% quartiles are given). Abbreviation: TAT, thrombin-antithrombin.

FIGURE 6 TAT complex concentrations in relation to antihirudin antibody formation. TAT complex concentrations did not differ between antihirudin antibody-positive (*, solid lines) and antihirudin antibody-negative (O, dotted lines) patients (median and 25% and 75% quartiles are given). Abbreviation: TAT, thrombin-antithrombin.

(Fig. 7); in about 2-3% of patients with antilepirudin antibodies, an inhibitory effect is seen (Huhle et al., 2001; Fischer et al., 2003). The biological effects of antilepirudin antibodies on anticoagulation can be easily compensated by changes in the lepirudin dose. Thus, ongoing daily aPTT measurements are recommended during lepirudin treatment, even when stable anticoagulation has been observed during the first 5 days.

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