An observational study in Coagulation Disorder, Blood and Prolonged APTT, sponsored by Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz. Recruiting at 16 sites in Spain. Per ClinicalTrials.gov, last updated 2026-09-11.
Sponsored by Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz · Observational
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.
This multicenter observational cohort study is designed to externally validate the APTTO predictive models in patients with prolonged APTT and normal prothrombin time evaluated in routine clinical practice across multiple hospitals, and to prospectively assess their perioperative clinical implementation and utility.
During the external-validation phase, the original APTTO model coefficients and predefined cut-offs are applied without recalibration, re-estimation, or modification of clinical management. Model discrimination, calibration, classification performance at the predefined cut-offs, decision-analytic performance, and robustness across clinical, analytical, and preanalytical conditions are evaluated.
At Hospital Universitario Fundación Jiménez Díaz, a prospective perioperative implementation phase begins on 1 October 2026. In eligible preoperative patients with isolated prolonged APTT, normal prothrombin time, and no clinically relevant bleeding history, APTTO is used as a clinical decision-support tool. In patients classified as low probability according to the prespecified pathway, hematological clearance for surgery may be issued without awaiting completion of deferred etiological testing, according to clinical judgment. The impact of implementation on time from Anesthesiology referral to hematological clearance, subsequent time to surgery, resource use, and perioperative safety is evaluated by comparison with the pre-implementation cohort.
From 1 January 2027, participating centers continue prospective recruitment restricted to a dedicated preoperative cohort using standardized perioperative pathway milestones and variables. Perioperative safety outcomes are assessed through 30 days after surgery.
No additional blood sampling or laboratory testing is required solely for research purposes.
The external-validation analyses are performed using the frozen APTTO models, without model updating or data-driven threshold optimization.
147 studies on the registry are indexed under Blood Coagulation Disorders; 15 are open to participants now.
This study's planned enrollment of 1,500 is above the median of 120 across 58 observational studies indexed under Blood Coagulation Disorders.
Browse Blood Coagulation Disorders studies →Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz is the lead sponsor of 76 studies on the registry; 27 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients of any age (pediatric and adult populations) undergoing coagulation testing with:
- Prolonged (APTT), defined as an APTT ratio ≥ 1.25.
- Normal prothrombin time (PT), according to local laboratory reference ranges.
Availability of clot waveform analysis (CWA) data obtained during routine APTT testing using:
Patients evaluated in either:
Exclusion Criteria:
2- Inadequate preanalytical conditions, defined as non-compliance with the study SOP, including but not limited to:
Inadequate centrifugation or plasma quality.
3. Absence of required CWA data or unavailable clot waveform images.
4. Samples in which APTT values are outside the measurable range of the analyzer, preventing extraction of CWA-derived parameters.
5- Patients with missing essential clinical or laboratory data required for application of the APTTO models.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with prolonged activated partial thromboplastin time (APTT) and normal prothrombin time undergoing routine laboratory evaluation. Clot waveform analysis (CWA) data and clinical information are collected prospectively as part of standard care and analyzed using the APTTO predictive models. No additional diagnostic or therapeutic procedures are performed.
Other: Clot waveform analysis-based risk stratification (APTTO models)
Application 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.
Time frame: Baseline (at the time of prolonged APTT laboratory assessment)
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.
Time frame: Baseline (at the time of prolonged APTT laboratory assessment)
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.
Time frame: Baseline (at the time of prolonged APTT laboratory assessment)
Overall prediction error of the APTTO model
Overall prediction error of the APTTO1 and APTTO2 models, assessed using the Brier score.
Time frame: Baseline (at the time of prolonged APTT laboratory assessment)
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.
Time frame: Baseline (at the time of prolonged APTT laboratory assessment)
Diagnostic accuracy of predefined APTTO cut-offs
Sensitivity, specificity, positive predictive value, and negative predictive value of predefined APTTO cut-offs for identifying pathological causes of prolonged APTT.
Time frame: Baseline (at the time of prolonged APTT laboratory assessment)
Interobserver agreement in clot waveform morphology classification
Agreement between local investigators and central reader (blinded to clinical data) for qualitative clot waveform morphology classification, assessed using Cohen´s kappa or Fleiss´kappa statistics, as appropriate.
Time frame: Baseline (at the time of prolonged APTT laboratory assessment)
Estimated impact of the APTTO algorithm on preoperative workflow
Estimated potential reduction in time to surgical cleareance and avoidance of additional etiologic testing based on application of the APTTO algorithm.
Time frame: Baseline (model-based estimation using timing data from index APTT laboratory assessment through surgical clearance)
Association between clot waveform morphology and severity of factor deficiency
Assessment of the association between clot waveform morphology, particularly strictly normal waveform patterns, and the severity of intrinsic pathway factor deficiencies in patients with prolonged activated partial thromboplastin time (APTT). This analysis aims to determine whether a normal waveform is associated with higher residual factor levels and a lower likelihood of clinically relevant deficiency. During the course of the study, additional exploratory objectives were incorporated to further investigate the clinical and physiological implications of clot waveform analysis. In particular, the relationship between strictly normal waveform morphology and the severity of factor deficiency will be evaluated prospectively in the remaining study cohort.
Time frame: During the preoperative evaluation period
Clinical impact of APTTO implementation in preoperative management
Evaluation of the clinical impact of implementing a clot waveform analysis-based diagnostic strategy (APTTO) in the preoperative management of prolonged activated partial thromboplastin time (APTT). This analysis will compare patients managed before and after implementation of APTTO at the development center, time to surgical clearance, and perioperative outcomes. This objective was incorporated during the course of the study to further assess the clinical implications of APTTO in routine practice and will be evaluated prospectively in the remaining study cohort.
Time frame: During the preoperative evaluation period and up to 30 days after surgery.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No — Individual participant data will not be shared publicly. Data will be analyzed in aggregated and pseudonymized form exclusively for the objectives of the study, in accordance with applicable data protection regulations and ethics committee approval.
Started Jan 2026 (actual). Primary completion is estimated for Mar 2027, 14 months after the start.
Of 29 observational studies under Blood Coagulation Disorders, half reached primary completion within 33 months of starting (the median), counting those still running; a quarter within 20 and three quarters within 59. This study's planned 14 months is below that.
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Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz