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Thromb Haemost 1996; 76(02): 166-170
DOI: 10.1055/s-0038-1650547
Original Article
Schattauer GmbH Stuttgart

Modulation of Plasma Fibrinogen Levels by Ticlopidine in Healthy Volunteers and Patients with Stable Angina Pectoris

Moniek P M de Maat
1   The Dept. Internal Medicine II, Erasmus University Rotterdam, The Netherlands
2   The Gaubius Laboratory TNO-PG, Leiden, The Netherlands
,
Alf E R Arnold
3   The Dept. Cardiology, Medical Center Alkmaar, The Netherlands
,
Stef van Buuren
2   The Gaubius Laboratory TNO-PG, Leiden, The Netherlands
,
J H Paul Wilson
1   The Dept. Internal Medicine II, Erasmus University Rotterdam, The Netherlands
,
Cornells Kluft
2   The Gaubius Laboratory TNO-PG, Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 01 March 1996

Accepted after resubmission 22 April 1996

Publication Date:
10 July 2018 (online)

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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.

 

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