To explore relevant changes in unexplained intraoperative bleeding, we evaluated elements of the final steps of the coagulation cascade in 226 consecutive patients undergoing elective surgery. Patients were stratified for the occurrence of unexplained intraoperative bleeding according to predefined criteria. Twenty patients (8.8%) developed unexplained bleeding. The median intraoperative blood loss was 1350 mL (bleeders) and 400 mL (nonbleeders) (P < 0.001). Fibrinogen and Factor XIII (F. XIII) were more rapidly consumed in bleeders (P < 0.001). Soluble fibrin formation (fibrin monomer) was increased in bleeders throughout surgery (P < or = 0.014). However, F. XIII availability per unit thrombin generated was significantly decreased in bleeders before, during, and after surgery (P < or = 0.051). Computerized thrombelastography showed a parallel, significant reduction in clot firmness. We suggest that mild preexisting coagulopathy is not rare in surgical patients and probably can result in clinically relevant intraoperative bleeding. This hemostatic disorder shows impaired clot firmness, probably secondary to decreased cross-linking (due to a loss of F. XIII, both in absolute measures and per unit thrombin generated). We suggest that the application of F. XIII might be worthwhile to test in a prospective clinical trial to increase clot firmness in patients at risk for this intraoperative coagulopathy.

We recently demonstrated that patients with intraoperative coagulopathy and increased blood loss show a persistent pre-, intra- and postoperative increase in fibrin monomer concentration as well as an excessive intraoperative consumption of fibrinogen and F. XIII. We therefore wanted to test the hypothesis that preoperative fibrin monomer concentrations can be used as a risk indicator for intraoperative blood loss. In 168 patients admitted to the surgical service of our hospital, median intraoperative blood loss increased significantly with preoperative fibrin monomer (FM) quartiles (50, 100, 200 and 400 ml in preoperative FM quartiles 1 to 4; p&lt;0.001, ANOVA on ranks and p&lt;0.05 for group wise comparison, Rank Sum test). Stratification in FM quartile groups was unrelated to diagnoses with the exception of laparoscopic cholecystectomy (found significantly less frequent in quartile 4 than 1). Most importantly, accuracy evaluation showed that preoperative fibrin monomer concentration &lt; 3 μg/l excluded intraoperative blood loss &gt; 500 ml with 92% sensitivity, 95% negative predictive value and 41% exclusion rate. This compares well to other exclusion strategies such as the exclusion of deep venous thrombosis with the help of D-dimer and probability scores. In contrast, blood loss was unrelated to preoperative values of prothrombin time, platelet count and actived partial thromboplastin time. The FM ROC curve compared to the PT ROC curve is shown in the figure; the area under the curve for the FM ROC curve was significantly greater than the one for the PT ROC curve (0.743, 95% CI 0.655 – 0.811 vs. 0.555, 95% CI 0.473 – 0.635). These results - obtained in a second, independent and prospective study - confirm the hypothesis generated from our first study that preoperative fibrin monomer concentrations allow prediction on excessive intraoperative blood loss. We suggest that preoperative fibrin monomer concentrations be further studied for identification of patients that might benefit from intensified intraoperative monitoring. Figure Figure