Factor XIII: recommended terms and abbreviations

Abstract

Blood coagulation factor XIII (FXIII) exists both in plasma and also in the cytoplasmic compartment of platelets, monocytes, their bone marrow precursors and monocyte-derived macrophages. FXIII present in the plasma is of tetrameric structure consisting of two potentially active A subunits and two carrier/inhibitory B subunits. In contrast, the cellular form of FXIII is a dimer of A subunits. Recombinant variants of the cellular form have also been produced [see review articles 1-4].The terminology and abbreviations used in the literature by different authors to designate different forms and subunits of FXIII have hitherto been rather variable and cause for confusion. At the ISTH SCC Subcommittee on FXIII meeting in Florence in 1997, a first proposal for unifying the nomenclature was presented. Members of the Subcommittee discussed the proposals, made several comments, and finally agreed upon a terminology and its use by Members of the Subcommittee. Since that time a number of scientists have been using the terminology proposed by the Subcommittee. However, the recommendations on nomenclature have never been published and have not been easily available. In consequence, the nomenclature used in the literature is still far from being unified, causing misunderstanding, and editors/publishers of scientific journals have not been aware of the recommendations.The main function of FXIII in plasma, upon activation by thrombin, is to cross-link fibrin and hence increase the stability of the clot. The field of FXIII research has, however, extended beyond the borders of hemostasis; for example, demonstration of FXIII in cells by immunohistologic and flow cytometric techniques became a marker reaction for the monocytic lineage, which has been proposed for the diagnosis or classification of malignant diseases [5][6][7]. It is of high importance therefore that a unified nomenclature on FXIII be used for these research areas as well, making it timely to update the original proposal and to publish the nomenclature in the official journal of ISTH. The recommendations presented here were unanimously approved by members of the FXIII Subcommittee at the 51st annual SSC meeting in Sydney, 2005, and relate to terms and abbreviated terms of different forms of FXIII, and its subunits, as well as intermediaries and end-products of FXIII activation. Recommended terms and abbreviations to designate different forms of FXIII zymogenBlood coagulation FXIII in general without specifying its form Recommended term: coagulation FXIII or FXIII. Recommended abbreviation: FXIII. FXIII normally present in the plasma (tetramer)Recommended term: plasma coagulation FXIII or plasma FXIII.

Functional factor XIII-A is exposed on the stimulated platelet surface

“…1 FXIII-A is present in platelets [22][23][24][25][26][27] in large quantities; a single platelet contains 60 6 10 fg, 28 making local platelet FXIII-A concentration around 150-fold greater than that in plasma. 29 Platelet FXIII-A, also known as cellular FXIII, 30 is largely stored in the cytoplasm 23,24 and, in contrast to FXIII-A 2 B 2 , can be nonproteolytically activated by Ca 21 alone. 31 Platelet-rich clots in vivo are much more resistant to lysis than whole blood clots.…”

Characterization of coagulation factor synthesis in nine human primary cell types

“…Because FXIIIA272829 plays an unambiguous role in the stabilization of the fibrin clot during wound healing and because thrombomodulin, an anticoagulant, functions in a complex with thrombin and is important for the degradation and lysis of fibrin after vascular repair, cells were also screened for the expression of FXIIIA and thrombomodulin. FXIIIA mRNA was expressed by monocytes, and proteomic analysis of highly purified platelets revealed that these cells also produce FXIIIA protein.…”

“…Monocytes have a direct and dual role in coagulation by producing important cofactors for FX (FV, FVIII and FXIIIA), but additional regulation is provided through the production of thrombomodulin, which destabilizes fibrin clots30, impairs platelet function27282930313233 and activates the anticoagulant protein C pathway. Furthermore, the observation that LPS can regulate coagulation factor production by monocytes shows that the system is dynamic and responds to local cues, further supporting the hypothesis that regulation of coagulation factor production is highly context dependent and much more complex than thought.…”

Recommendations for nomenclature on fibrinogen and fibrin

“…Fibrin structure is reinforced by activated factor XIII (FXIIIa) [21], which forms covalent bonds between the γ and α chains resulting in γ‐γ dimers and α polymers. To a chemist, transglutaminases such as FXIIIa catalyze ligation rather than cross‐linking [22].…”