Agents

Abstract

Sir I read with interest the review by Seyednejad et al. on topical haemostatic agents. The authors have made a tremendous effort to give an overview of all available clotting agents and their advantages and disadvantages. Nevertheless, I would like to point out an error in figure 5 of the review. This figure depicts the relationship between different topical agents and components of the clotting cascade such as the intrinsic and extrinsic pathways. More than 5 years ago, the conceptual thoughts about the functional components of the coagulation pathway changed. In the sixties, the cascade and waterfall hypotheses proposed an intrinsic pathway of coagulation initiated by contact factors. The extrinsic tissue factor pathway was thought to play an ancillary role in activation of coagulation. The segregation of the coagulation system into the intrinsic and extrinsic pathways fails to reflect coagulation accurately. The current view is that coagulation predominantly proceeds by the tissue factor/factor-VIIa pathway. Thrombin is generated after exposure of F VIIa to TF and subsequent activation of factor X into Xa. Both TF/F-VIIa complex and F Xa are inhibited by tissue factor pathway inhibitor. Interaction of the cofactor molecule factor V with factor Xa results in increased thrombin generation. The TF/F-VIIa pathway has several amplification loops, which maintain Xa generation via positive feedback mechanisms involving factors VIII, IX and XI. Thrombin generation is downregulated by antithrombin and activated protein C. Thus, currently a more holistic view is held on activation of coagulation and its amplification and inhibition loops than two pathways that both separately end in thrombin formation. M. A. Boermeester Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands DOI: 10.1002/bjs.6602 Authors’ reply: Topical haemostatic agents (Br J Surg 2008; 95: 1197–1225)