J Thromb Haemost. 2025 Dec 22:S1538-7836(25)00906-7. doi: 10.1016/j.jtha.2025.11.025. Online ahead of print.
ABSTRACT
INTRODUCTION: Rare coagulation factor deficiencies (RCFDs) can cause significant bleeding, but APTT and PT may not detect abnormalities, and factor activity measurements do not predict bleeding severity (BS). Thrombin generation assays may better reflect overall hemostatic capacity. This study investigates whether thrombin generation can detect RCFDs and correlate with bleeding severity in patients with congenital deficiencies of factors II, V, V/VIII, VII, X, and XI.
METHODS: Thrombin generation was measured using the Nijmegen Hemostasis Assay (NHA) in patients from the cross-sectional Dutch RBiN study (2017-2019). Parameters analyzed included thrombin potential (TP), lag time (LT), and TP/LT ratio, normalized using pooled normal plasma and expressed as percentages of the mean from 37 healthy controls. NHA data were correlated with BS and compared with APTT and PT.
RESULTS: We included 106 patients, mostly with mild deficiencies (median factor activity 5-53%). Overall, thrombin generation was significantly reduced compared to controls, with decreased thrombin potentials (median 58%) and prolonged lag times (150%), resulting in reduced TP/LT ratios (45%). These parameters correlated with BS; across RCFDs, median TP/LT ratios ranged from 30-104% in patients without spontaneous bleeding (BS 0-1), 26-49% in mild spontaneous bleeding (BS 2), and 0-22% in severe spontaneous bleeding (BS 3). At 95% specificity, TP/LT ratio showed 68-100% sensitivity, outperforming APTT and PT (14-80%) in all RCFDs except FVII and FV/FVIII deficiency.
CONCLUSION: Thrombin generation profiling correlated with BS and showed higher sensitivity than conventional screening assays in detecting RCFDs, supporting its potential in screening and clinical evaluation of RFCDs.
PMID:41443372 | DOI:10.1016/j.jtha.2025.11.025