Feasibility to infer accurate fibrinogen concentrations from thrombin generation, prothrombin time, or Reptilase time waveforms

Background: A rapid point-of-care test to measure fibrinogen levels is crucial to adequately treat major blood loss, eg, because of trauma, postpartum hemorrhage, or major surgery. Obtaining results from current fibrinogen assays is too time-consuming in emergency situations. We have developed mathematical methods to infer fibrinogen concentrations from the turbidity waveforms of the thrombin generation (TG), prothrombin time (PT), and Reptilase time (RT) assays. Objectives: The aim of this study was to verify the performance of these methods using assay waveforms from real-world patient samples. Methods: We measured TG, PT, and RT in 44 plasma samples with a wide range of fibrinogen levels (1.1-16.6 g/L), high D-dimer, prolonged PT, and/or containing anticoagulant medication. Results: Overall, data from the PT (R = 0.965) and RT (R = 0.985) assays could be used as data input to accurately infer fibrinogen levels for all patients. The TG assay (R = 0.917) was less robust and generated results for only 36 patients. Conclusion: Our mathematical methods proved to be able to accurately infer a wide range of fibrinogen levels in real-world patient samples, even in the presence of anticoagulant medication. With this study, we took the first step toward the development of a new, rapid point-of-care fibrinogen test.