Introduction
There is increasing clinical and laboratory interest in the measurement of both plasma
fibrinogen and fibrin D-dimer to predict arterial thrombotic events, such as cardiovascular
death, myocardial infarction (MI), stroke, leg ischemia, arterial surgery (e.g., angioplasty,
bypass grafting), and postsurgical arterial occlusion. There are several possible
reasons for such interest.
First, there is substantial evidence from prospective studies that the plasma fibrinogen
level is a strong, consistent predictor of such cardiovascular events in people with
or without clinically detectable arterial disease. Furthermore, fibrinogen adds to
the predictive valve of major conventional risk predictors (e.g., smoking, blood pressure,
serum cholesterol) in healthy people (Fig.1).1-7
Second, we and others have shown, in several prospective studies, that plasma fibrin
D-dimer (measured quantitatively by enzyme-linked immunosorbent assays [ELISAs]) is
also a strong, consistent predictor of such cardiovascular events in people with or
without clinically detectable arterial disease.8-14 Again, fibrin D-dimer may add to the predictive value of major conventional risk
predictors (e.g., smoking, blood pressure, serum cholesterol, plasma fibrinogen) in
healthy people (Fig. 2).
Third, there are several interactive, plausible, potential biological mechanisms through
which increasing plasma fibrinogen levels, which are due to multiple gene-environment
interactions, may promote ischemic events. These include increased blood viscosity,
atherogenesis, and platelet-fibrin thrombogenesis (Fig. 3). Increased plasma D-dimer
levels are a marker of turnover of cross-linked fibrin, whether vascular or extravascular
(Fig. 3).
Fourth, not only is there more evidence for fibrinogen and D-dimer as predictors of
arterial thrombotic events than for other hemostatic or thrombotic variables, but
these two assays are more stable and more practical to measure in clinical and epidemiological
studies. These tests are also already available in many district hospitals for the
diagnosis of disseminated intravascular coagulation (DIC) and, in the case of D-dimer,
venous thromboembolism.15,16 As with other major cardiovascular risk factors (e.g., smoking, blood pressure, serum
cholesterol), there is a need for standardization of both fibrinogen assays17-23 and D-dimer assays.24
Finally, clinical interest in plasma assays of fibrinogen also may increase in the
event that ongoing clinical trials of plasma fibrinogen reduction (e.g., with certain
fibrates or ancrod) show that such treatments are beneficial.25 Likewise, clinical interest in plasma assays of D-dimer may also increase if future
studies show that oral anticoagulant prophylaxis is the most costeffective and risk-effective
in people with elevated plasma D-dimer levels, who are normalized by full-dose warfarin.15,19,26-28 This review discusses each of these aspects of fibrinogen and fibrin D-dimer.
