Prolonged activated partial thromboplastin time (APTT) is a frequent laboratory finding that may reflect a broad spectrum of underlying conditions, ranging from benign laboratory abnormalities to clinically relevant hemostatic disorders. Clot waveform analysis (CWA), automatically generated during routine APTT testing by optical coagulation analyzers, provides additional quantitative and qualitative information on clot formation dynamics.
The APTTO model is a previously developed two-step predictive algorithm based on CWA features designed to estimate the probability of a pathological cause of prolonged APTT and to differentiate lupus anticoagulant from intrinsic pathway factor deficiency or von Willebrand disease. Internal validation has demonstrated good discrimination and calibration.
This multicenter observational study aims to perform an external validation of the APTTO model in independent patient cohorts, assessing its discrimination, calibration, and decision-analytic performance without model updating.
Optical coagulation analyzers (ACL TOP platform).
Silica-based APTT reagent (SynthASil®).
Completion of the standard laboratory evaluation for prolonged APTT as part of routine clinical care, when clinically indicated.
Samples collected and processed in accordance with the standardized preanalytical protocol defined in the study SOP.
Prolonged prothrombin time (PT) or combined prolongation of PT and APTT.
Incorrect blood-to-anticoagulant ratio.
Delayed plasma processing beyond protocol-defined time limits.
Inadequate centrifugation or plasma quality.
The study population includes pediatric and adult patients undergoing routine coagulation testing in clinical practice who present with isolated prolongation of activated partial thromboplastin time (APTT) and normal prothrombin time (PT). Patients may be evaluated in the preoperative setting or during routine clinical care for other indications. All laboratory data, including clot waveform analysis (CWA), are generated as part of standard diagnostic procedures, without additional blood sampling or modification of clinical management. Patients receiving anticoagulant therapy that may prolong APTT are included, provided that PT remains within the normal range. The study uses pseudonymized data obtained from electronic medical records and laboratory systems, with no direct patient contact and no anticipated risks beyond routine care.
Cohort
Prospective
Clot waveform analysis-based risk stratification (APTTO models)
Other interventionApplication of the APTTO predictive models (APTTO1 and APTTO2) to clot waveform analysis parameters generated during routine activated partial thromboplastin time testing, for research purposes only. The model output does not influence clinical management or surgical decision-making during the study.
Discriminatory performance of the APTTO model
Discrimination of the APTTO1 and APTTO2 models for identifying the cause of prolonged activated partial thromboplastin time (APTT), assessed by the area under the receiver operating characteristic curve (AUC) in an independent multicenter cohort.
Calibration-in-the-large of the APTTO model
Calibration-in-the-large of the APTTO1 and APTTO2 models assessing agreement between predicted and observed probabilities in an independent multicenter cohort.
Calibration slope of the APTTO model
Calibration slope of the APTTO1 and APTTO2 models, evaluating the relationship between predicted and observed risk across the probability spectrum.
Overall prediction error of the APTTO model
Overall prediction error of the APTTO1 and APTTO2 models, assessed using the Brier score.
Clinical utility of the APTTO model assessed by decision curve analysis
Net clinical benefit of the APTTO models compared with investigate-all and investigate-none strategies, assessed by decision curve analysis across clinically plausible threshold probabilities.
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