Summary
Elevated plasma fibrinogen levels are associated with an increased risk for cardiac
events. Ticlopidine is a drug that inhibits the ADP-induced aggregation of blood platelets
and it also has been described that ticlopidine can decrease the plasma fibrinogen
level in patients with vascular diseases. The mechanism of this decrease has not yet
been elucidated and therefore mechanisms that are known to affect fibrinogen levels
were studied, viz. the acute phase reaction, total fibrin plus fibrinogen degradation
(TDP) levels and the polymorphisms of the fibrinogen β-gene.
The fibrinogen lowering effect of ticlopidine was studied in 26 healthy volunteers,
selected on genotype of the BclI polymorphism of the fibrinogen β-gene, and in 26 patients with stable angina pectoris
in a double blind, randomized cross-over study. Functional plasma fibrinogen levels
were measured with the Clauss assay. Fibrinogen antigen, C-reactive protein (CRP)
and TDP levels were measured using an enzyme immuno assay (EIA).
In the healthy volunteers the functional fibrinogen levels had decreased by 0.20 g/l
(9%, p = 0.005 using the paired Student t-test) after 4 weeks of 250 mg bid ticlopidine
administration, whereas fibrinogen antigen, CRP and TDP levels were not significantly
changed. In the stable angina pectoris patients the pre-treatment fibrinogen, CRP
and TDP levels were significantly higher than in the volunteer group. After four weeks
250 mg bid ticlopidine administration the functional fibrinogen levels had decreased
by 0.38 g/l (11%, p < 0.005), whereas the fibrinogen antigen, CRP and TDP levels were
not significantly changed. The levels of functional and antigen fibrinogen, CRP and
TDP did not change significantly during the placebo period in the volunteers or the
patients. Neither in the volunteers nor in the patients was the effect of ticlopidine
on the fibrinogen levels associated with the fibrinogen β-gene polymorphisms.
Therefore, the fibrinogen lowering effect of ticlopidine is likely to be a modulation
of the functionality of the molecule and unlikely to be modulated by the acute phase
reaction, TDP-levels or the fibrinogen β-gene polymorphisms.
