F. XIII in perioperative coagulation management

Unexplained intra-operative coagulopathies continue to be a diagnostic and therapeutic dilemma. The pathophysiology behind unexplained intra-operative coagulopathies is of great variety and complexity (pre-existing coagulopathies, dilutional coagulopathy, interactions of medications, etc.). We have shown in prospective studies that patients undergoing elective surgery who develop ’unexplained' intra-operative bleeding have significantly less F. XIII per unit thrombin available at any point in time (i.e., also already preoperatively) than patients without such coagulopathies. The consequence is a significant loss of clot firmness associated with an increase in intra-operative blood loss. Thus, these patients have less cross-linking capacity to begin with, which explains their preoperatively increased fibrin monomer concentration. It is important to note that the acquired (or compared with the amount of thrombin generated ’relative') F. XIII deficiency in situations with surgical stress shows early clinical relevance (i.e., clinical manifestation occurs even with only mild-to-moderate deficiency); this differs from the experiences with patients with congenital F. XIII deficiency, where a pronounced deficiency must be present to have clinically significant (spontaneous) bleeding. Patients undergoing elective surgery and having increased preoperative fibrin monomer concentration (as a marker of decreased cross-linking capacity) are at risk for increased intra-operative blood loss. At least one proof-of-principle landmark study suggests that such patients benefit from treatment with F. XIII early intra-operatively. This new concept helps to explain the pathophysiology behind unexplained intra-operative coagulopathies and thus allows for corresponding treatment strategies.

Keywords: unexplained bleeding, intra-operative coagulopathy, factor XIII, cross-linking, fibrin monomer