Investigation and Characterization of Clotting Artifacts in Coagulation Testing for the Development of Screening...

Coagulation tests are crucial for diagnosing hemostatic disorders. However, preanalytical errors, particularly sample clotting, may compromise test accuracy and lead to clinical misinterpretation. As not all clots are detectable by visual inspection, this study characterized clotted citrated samples to establish objective criteria for clot identification.

Routine coagulation assays-including PT, APTT, fibrinogen, D-dimer, FDP, fibrin monomer complex (FMC), plasmin-α2 plasmin inhibitor complex (PIC), and thrombin-antithrombin complex (TAT)-were performed, and 101 paired specimens from 101 patients who required blood recollection were analyzed. Among the 77 specimens with visible clots, coagulation profiles were analyzed to identify cut-off values and develop logistic regression models. The models were subsequently validated using an additional 24 abnormal but clot-free specimens.

Clotted samples showed significantly shortened APTT and elevated FDP, FMC, PIC, and TAT levels. Shortening of APTT by ≥ 3.1 s relative to the reference was a reliable indicator of clotting. Combining APTT with TAT or FMC provided high diagnostic accuracy (AUC: 0.969 and 1.000, respectively). We established a "Clotting Score" to assess sample viability even without visible clots. FDP and PIC increased progressively with time in clotted samples.

Sample clotting substantially affects the accuracy of coagulation tests. Shortened APTT and elevated FMC and TAT serve as reliable indicators, with FDP and PIC offering time-sensitive supplementary clues. This multimodal approach could help standardize criteria for sample rejection and recollection, thereby improving test reliability and supporting clinical decisions.