Introduction The thrombin generation assay‐calibrated automated thrombogram (TGA‐CAT) method is used to measure the overall coagulation capacity in plasma. However, the method is still considered to be a research tool, mainly because of its’ lack of standardization. Aim Our study aimed to further raise the standardization level for the TGA‐CAT method by evaluating a detailed standardization protocol and three reference plasmas’ (RP)s ability to normalize results. Methods Six Nordic centres participated in the study, and with input from all centres a detailed laboratory standardization protocol based on the TGA‐CAT manual of the manufacturer was established. Three types of plasma, hypo‐,normal and hypercoagulable plasma were assessed. Three commercial lyophilized RPs were used for normalization of data. All samples were aliquoted at the Malmö centre and sent frozen at −20˚C to participating centres. Results Before normalization, all results under all testing conditions showed inter‐laboratory coefficient of variability of 10% or lower except for endogenous thrombin potential (12%) and peak (14%) in hypo‐plasma with 1 pmol/L tissue factor as starting agent. Successful normalization, improving variability in results, was obtained with two of the three evaluated RPs (HemosIL RP and Affinity RP). Conclusion With our standardization concept, we were able to produce TGA‐CAT results as robust as standard coagulation assays used in the routine laboratories. Normalization with HemosIL RP may be considered in populations with low or unknown coagulability, while when analysing plasma samples from populations where hypercoagulability is known or suspected, normalization with Affinity RP may be preferred.

Fresh and ft-PRP cannot be assumed to show equal results in the TGA-CAT assay.

Background In a previous smaller study, we found evidence of a diminished global coagulation capacity after maximal exercise in patients with severe haemophilia A (HA). Aim To validate these results, we repeated the study in a larger cohort. We also examined if the exercise‐induced increased levels of von Willebrand factor (VWF) might prolong the effect of factor concentrate administered just before exercise. Methods We studied individual and global coagulation parameters after maximal physical exercise in 10 persons with severe HA and 10 healthy matched control subjects. Blood samples were taken before, 10 minutes, 60 minutes and 4 hours after exercise. Results Rotational thromboelastometry (ROTEM) and thrombin generation assay‐calibrated automated thrombogram (TGA‐CAT) showed significantly increased coagulation capacity after maximal exercise in healthy controls but not in patients with severe HA. VWF antigen and activity levels increased significantly in both groups, whereas FVIII:C only showed a significant increase in the control group. No statistically significant differences were seen between FVIII pharmacokinetic results obtained with and without exercise. Conclusion Our findings do not support the presence of a FVIII‐independent mechanism that increases global coagulation, but rather underscores the importance of FVIII in mediating the increased coagulation capacity seen after exercise. Our results could not support the hypothesis that exercise‐induced increased levels of VWF for patients with severe HA lead to a prolonged effect of factor concentrate administered just before exercise.

Platelet transfusion refractoriness is a serious clinical concern that complicates the management of thrombocytopenic patients. Previous studies have suggested a potential role for both complement and platelet activation based on in vitro analyses of platelet concentrates. In this study, the post-transfusion platelet response, as indicated by the corrected count increment at 1 and 24 h after prophylactic platelet transfusions, respectively, was correlated with the 1 h post-transfusion Δconcentration (1 h post-transfusion -pretransfusion) of complement and platelet activation biomarkers. The study was registered as a clinical trial at ClinicalTrials.gov (identifier: NCT02601131) and patients were recruited during inpatient care in the hematological department. Soluble terminal complement complexes, soluble P-selectin and soluble CD40 ligand were analyzed. Confirmed alloimmunized patients were excluded. Included subjects were either given platelet transfusions (n = 43) and categorized into four clinical study groups or included in a non-transfused control group (n = 10). In total, 54 transfusions were included. No transfusion-mediated complement activation was observed. The transfusions were associated with a significant increase in the concentration of soluble P-selectin (p < .001), primarily corresponding to the passive infusion of soluble P-selectin-containing plasma residuals. The Δconcentration of soluble P-selectin was, however, not significantly correlated with the corrected count increments. Thus, significant correlations between biomarkers of complement and platelet activation and the post-transfusion platelet response could not be demonstrated in this study.