γ′ Fibrinogen as a novel marker of thrombotic disease

Abstract

Abstractγ ′ Fibrinogen is an isoform of fi brinogen that normally constitutes about 7 % of total plasma fi brinogen, and arises from an alternative processing event in the γ chain mRNA. γ ′ Fibrinogen is a newly-emerging cardiovascular disease (CVD) risk factor that appears to have an independent association with CVD from that of total fi brinogen, which is itself a well-established CVD risk factor. γ ′ Fibrinogen shows a signifi cant association with coronary artery disease and myocardial infarction in at least four case-control studies, including the Stockholm Coronary Artery Risk Factor study and the Framingham Heart Study. γ ′ Fibrinogen is also signifi cantly associated with stroke, as shown in the Erasmus Stroke Study and others. The role of genetic polymorphisms in the association between γ ′ fi brinogen and CVD is under active investigation. γ ′ Fibrinogen increases during infl ammation, and is differentially regulated from total fi brinogen under pathologic conditions, as demonstrated in the Periodontitis and Vascular Events study. The association between γ ′ fi brinogen and venous thromboembolism remains unclear, however, with some studies showing an inverse association with γ ′ fi brinogen levels and other studies showing the opposite.

Evidence that fibrinogen γ′ regulates plasma clot structure and lysis and relationship to cardiovascular risk factors in black Africans

“…19 Fibrinogen g9 is thought to be related to cardiovascular disease (CVD) risk independent of total fibrinogen concentration. 11,20 Therefore, not only factors that affect g9 fibrinogen levels but also factors that could potentially influence the g9/total fibrinogen ratio should be determined.…”

Prospective study of γ′ fibrinogen and incident venous thromboembolism: The Longitudinal Investigation of Thromboembolism Etiology (LITE)

“…First, γ′ fibrinogen rises in the acute phase response [4], and higher levels strengthen clots by altering fibrin formation and structure and making clots resistant to fibrinolysis [4, 23, 24]. These properties may help explain why some studies have found higher γ′ fibrinogen associated with increased risk of atherothrombotic vascular disease [4, 5]. On the other hand, the γ′ isoform binds less strongly than does the γA isoform to platelets, possibly reducing platelet activation [25].…”

“…Despite a possible positive association of γ′ fibrinogen with atherothrombotic events in Framingham and several other epidemiological studies [4], studies of VTE have mostly reported the opposite association. For example, the Leiden Thrombophilia Study reported that having a FGG -H2 haplotype, which was strongly related to lower circulating γ′ fibrinogen, doubled the risk of VTE.…”

“…γ′ fibrinogen comprises approximately 10% of total plasma fibrinogen in the plasma, but the proportion varies among individuals and rises during an acute phase response. In the presence of factor XIII, clots made from γ′ fibrinogen are more resistant to lysis than normal clots; therefore the proportion of γ′ fibrinogen was hypothesized to be a risk factor for arterial thrombosis [4]. The Framingham Study reported that plasma γ′ fibrinogen was associated positively with prevalent arterial cardiovascular disease (odds ratio = 1.5 for the highest versus lowest γ′ fibrinogen tertiles), independent of total fibrinogen [5].…”

Influence of type 2 diabetes mellitus on Khorana venous thromboembolism risk in colorectal cancer patients

“…The increase of FIB concentration is often considered as a risk factor for cardiovascular disease and thrombosis (30). Besides, a number of studies have confirmed the predictive value of D-dimer levels for venous thromboembolism (16).…”