The diagnosis of FX is usually suspected when both the prothrombin time (PT) and activated partial thromboplastin time (aPTT) are abnormal and correct with a 1:1 mix with normal plasma. Factor X functional activity (FX:C) is quantified by performing serial dilutions with FX-deficient plasma. PT reagents may vary in sensitivity to FX deficiency and congenital variants have been identified in which both the PT and PTT are normal.30 An additional assay that is available for protein characterization is the Russell viper venom (RVV) time. RVV is a metalloproteinase that directly activates FX (as well as FV, prothrombin, and fibrinogen) and will detect deficiency of FX if FX-deficient plasma is used as substrate. Immunological assays, such as enzyme-linked immunosorbent assays, measure FX antigen (cross-reacting material). Chromogenic assays use a FXa-sensitive chromophoric substrate that is detected spectrophotometrically. Immunologic and chromogenic assays may miss cases of dysfunctional FX and therefore should not be used as screening tests for FX deficiency.
A proposed classification schema for clinical purposes is based on clotting, chromogenic, and immunologic characteristics. Girolami et al41 describe a proposed classification based on cross-reactive material (CRM) status. Type I is cross-reactive material (CRM) negative. Type II is CRM positive. Type III is CRM positive with dysreactive protein, including defects in all activity systems except RVV activation (Friuli like), defects only (or predominantly) in the extrinsic-Xase system (Padua like), defects only (or predominantly) in the intrinsic-Xase system (Melbourne like), or defects with discrepant (high) chromogenic assays. Type IV includes cases of FX deficiency associated with FVIII deficiency due to chromosome 13 abnormalities. It should be noted that consensus on the use of this classification has not been reached.
Rare Coagulation Disorders Resource Room, an extension of the RBDD Registry (eu.rbdd.org), was developed in collaboration with the Indiana Hemophilia & Thrombosis Center (www.innovativehematology.org).
The Resource Room serves as a platform to promote international collaboration to increase knowledge of these very rare disorders and to improve the care of affected individuals. The international RBDD mission, under the leadership of Dr. Peyvandi, will continue to be expanded over time.
The Resource Room thanks all contributing authors of the website articles that have made this valuable information available to the global community of both individuals affected with rare coagulation disorders and their healthcare providers.
