The (Patho)physiology of Fibrinogen γ′

Fibrinogen γ′ is a splice variant of the fibrinogen γ-chain, which leads to a negatively charged extension at the C-terminus of the γ-chain. In fibrinogen, the splice variant appears mainly as a heterodimer with the common γA chain, as γA/γ′ fibrinogen. This variant has been shown to modulate thrombin and factor XIII (FXIII) activity, influence clot architecture, and lack a platelet-binding site. Clinically γA/γ′ fibrinogen levels have been associated with arterial and venous thromboses, indicating that the functional effects of γA/γ′ fibrinogen may contribute to the pathology of thrombosis. In view of the fact that the splice variant has several functional effects and is found so far in all individuals, this review provides an up-to-date summary of the key biologic aspects of this fibrinogen variant and discusses any inconsistencies in current reports.