ArticleResearch and practice in thrombosis and haemostasis2025
Algorithm-based effective recognition of acquired hemophilia A and other causes of isolated prolonged activated partial thromboplastin time within large blood sample series.
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Abstract
Background: Among the various causes of isolated prolonged activated partial thromboplastin time (aPTT), acquired hemophilia A (AHA) is a rare disorder whose timely recognition is often missed clinically. Consequently, there is a need for a laboratory approach that allows for rapid and reliable evaluation of the causes of an isolated prolonged aPTT within large series of blood samples without specific diagnostic hypotheses. Objectives: To create and implement an automated sequential laboratory-based algorithm to facilitate early AHA diagnosis.' in a new line below the Background section in the Abstract. Methods: A multistep automated algorithm was developed and validated to target blood samples sent for routine coagulation assays, actively excluding samples with an underlying anticoagulant treatment, selecting those with an isolated prolonged aPTT, and detecting clinically relevant causes. Results: The main causes of an isolated prolonged aPTT were anticoagulant drugs and factor (F)XII deficiency/consumption (∼75% of cases). Selection of samples with an isolated prolonged aPTT was achieved by the first 5 automated steps (24 h/7 d), based on routinely available data. During a prospective 3.25-year trial, this strategy enabled the identification of 0.5% (1816/359,229) of samples. After FXII testing (step 6) and exclusion of undisclosed anti-FXa activity (step 7), evaluation of specific causes identified 6.5% (119/1816) of FVIII-deficient samples, including known cases of congenital hemophilia or von Willebrand disease, and 3 new cases of AHA. Since its routine implementation, 4 additional patients with AHA were identified. In all 7 patients, the laboratory-based diagnosis was achieved on the first day of hospitalization without any preceding clinical suspicion for AHA. Conclusion: Our sequential laboratory-based algorithm enables the rapid and accurate identification of rare causes of isolated prolonged aPTT, which can lead to clinically significant bleeding disorders, such as acquired hemophilia.
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