Summary
Fibrinogen has recently emerged as a major risk factor for athero- thrombosis. However,
the pathophysiologic mechanism linking high fibrinogen concentration to cardiovascular
disease is unclear.
In this study 136 subjects (75 males, 61 females, age 51.7 ± 14.4 years, mean ± standard
deviation, range 17-82) were tested for total and HDL-cholesterol, total triglycerides,
apolipoprotein AI, apolipo- protein B, fibrinogen, prothrombin fragment and D-dimer.
Moreover, 5 subjects who had hyperfibrinogenemia (range 450 to 950 mg/dl) for at least
6 months by repeated measurements, were treated with a short 7-day course of heparin
12,500 U/day subcutaneously. The effect of heparin on all the above mentioned parameters
was observed at the end of treatment and after 7 days of wash-out. Simple regression
analysis detected a positive correlation between fibrinogen and age, prothrombin fragment
and D-dimer, and a negative correlation between fibrinogen and HDL-cholesterol and
apolipoprotein AI. A direct correlation between age and both prothrombin fragment
and D-dimer was also demonstrated. Multivariate analysis showed a persistent correlation
between fibrinogen and prothrombin fragment, D-dimer and age, that was not influenced
by sex, smoking habit and body mass index. In the 5 hyperfibrinogenemic subjects,
heparin administration significantly reduced fibrinogen (625.4 ± 211.1 vs 455.2 ±
112.3 mg/dl, p <0.03), prothrombin fragment (0.97 ± 0.1 vs 0.63 ± 0.2 nM, p <0.002)
and D-dimer (336 ± 101.8 vs 275.2 ± 78.5 ng/ml, p <0.03). All these parameters returned
to baseline after 7 days of wash-out (fibrinogen 632.5 ± 198.2 mg/dl, prothrombin
fragment 0.96 ± 0.2 nM, D-dimer 325.8 ±98.65 ng/ml).
These data indicate that fibrinogen plasma levels are strongly correlated to parameters
of thrombin activation in plasma and suggest that high fibrinogen plasma levels might
be a risk marker for cardiovascular disease because expression of an existing thrombophilia.
