External Multicenter Validation of the APTTO Model for Prolonged APTT Using Clot Waveform Analysis

NCT07418099 | Recruiting

• 2 other identifiers: APTTO-EXT-IISFJD-2026Pending ethics committee aprov
• Study Type: observational
• Target: 1,500
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

Coagulation Disorder, Blood; Prolonged APTT

Keywords

Activated Partial Thromboplastin Time; Prolonged APTT; Clot Waveform Analysis; CWA; Preoperative Assessment; Predictive Model; Diagnostic Algorithm; Risk Stratification; Decision Support Systems; Hemostasis; Coagulation Disorders; Lupus Anticoagulant; Coagulation Factor Deficiency; von Willebrand Disease; Laboratory Automation; Clinical Decision-Making; Surgical Delay; Resource Utilization

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline (at the time of prolonged APTT laboratory assessment)

Secondary Outcomes (9)

• Calibration-in-the-large of the APTTO model

  Baseline (at the time of prolonged APTT laboratory assessment)

• Calibration slope of the APTTO model

  Baseline (at the time of prolonged APTT laboratory assessment)

• Overall prediction error of the APTTO model

  Baseline (at the time of prolonged APTT laboratory assessment)

• Clinical utility of the APTTO model assessed by decision curve analysis

  Baseline (at the time of prolonged APTT laboratory assessment)

• Diagnostic accuracy of predefined APTTO cut-offs

  Baseline (at the time of prolonged APTT laboratory assessment)

Study Arms (1)

Patients with prolonged activated partial thromboplastin time (APTT)

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)

Interventions

Clot waveform analysis-based risk stratification (APTTO models) OTHER

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.

Patients with prolonged activated partial thromboplastin time (APTT)

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• Patients of any age (pediatric and adult populations) undergoing coagulation testing with:
• \- Prolonged activated partial thromboplastin time (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:
• 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.
• Patients evaluated in either:
• Preoperative assessment, or
• Routine clinical practice (non-preoperative setting).

You may not qualify if:

• Prolonged prothrombin time (PT) or combined prolongation of PT and APTT.
• Inadequate preanalytical conditions, defined as non-compliance with the study SOP, including but not limited to:
• Incorrect blood-to-anticoagulant ratio.
• Delayed plasma processing beyond protocol-defined time limits.
• Inadequate centrifugation or plasma quality.
• \. Absence of required CWA data or unavailable clot waveform images.
• \. Samples in which APTT values are outside the measurable range of the analyzer, preventing extraction of CWA-derived parameters.
• Patients with missing essential clinical or laboratory data required for application of the APTTO models.

Sponsors & Collaborators

• Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz: lead

Study Sites (16)

Hospital Universitario Severo Ochoa

Leganés, Madrid, Spain

RECRUITING

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

RECRUITING

Hospital Universitario Arnau De Vilanova

Lleida, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Spain

RECRUITING

Hospital Universitario Clínico San Carlos

Madrid, Spain

NOT YET RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, Spain

RECRUITING

Hospital Universitario Gregorio Marañón

Madrid, Spain

NOT YET RECRUITING

Hospital Universitario Puerta de Hierro

Madrid, Spain

NOT YET RECRUITING

Hospital Universitario Ramón y Cajal

Madrid, Spain

RECRUITING

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, Spain

NOT YET RECRUITING

Clínica Universidad de Navarra

Pamplona, Spain

NOT YET RECRUITING

Hospital Clínico Universitario de Salamanca

Salamanca, Spain

NOT YET RECRUITING

Complexo Hospitalario Universitario de Santiago

Santiago de Compostela, Spain

NOT YET RECRUITING

Hospital Clínico Universitario de Valladolid

Valladolid, Spain

RECRUITING

Complexo Hospitalario Universitario De Vigo

Vigo, Spain

NOT YET RECRUITING

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Spain

NOT YET RECRUITING

MeSH Terms

Conditions

Blood Coagulation Disorders; Hemostatic Disorders; von Willebrand Diseases

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Blood Platelet Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Diego Velasco Rodríguez, MD, PhD

  Hospital Universitario Fundación Jiménez Díaz / IIS-FJD

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Diego Velasco Rodríguez, MD, PhD

CONTACT

+34 669 98 04 32; diego.velascor@quironsalud.es

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 26, 2026
• First Posted: February 18, 2026
• Study Start: January 13, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (16)