Reference intervals and biological variation in parameters of the thrombin generation test in healthy individuals

Introduction: Establish the referenceintervals (RIs) and analyze biological variability (BV) to introduce the thrombin generation test (TGT) into clinical practice.Methods: To determine the RIs parameters of TGT, we analyzed platelet-poor plasma (PPP) (n = 123), rich (PRP) (n = 76), and microparticle-mediated TGT (MP-TGT) (n = 32) in healthy participants. For the BV study, we collected samples from five participants over 5 weeks. A nested analysis of variance (ANOVA) was performed to evaluate the BV results.Results: The between-individual variation (CVG), within-individual variation (CVI), analytical variation (CVA) for TGT on PPP for all parameters were from 5.5% to 17.3%, 5.4% to 17.7%, and 2.6% to 5.3%, respectively. For PRP, the CVG, CVI, and CVA were ranged from 3.0% to 23.7%, 8.4% to 23.0%, and 4.1% to 6.9%, respectively. The index of individuality (II) ranged from 0.3 to 3.1 for PPP and from 0.3 to 4.5 for PRP. The reference change value (RCV) for PPP was from 19.8% to 50.1%, while for PRP, it was 27.2% to 66.5%. We recommend using the RIs for the parameters ETP (nM/min): 1101.6-2332.1 and Peak (nM): 163.5-381.3 for PPP and ETP (nM/min): 1088.5-2634.9; Peak (nM): 72.6-210.7 for PRP. The resulting MP-TGT are highly dependent on age require a larger sample.Conclusion: For TGT on PPP and PRP the RIs developed on our population for Peak and ETP parameters can be used. Time parameters: Lagtime and ttPeak, min with II < 0.6, require monitoring over time with RCV calculation.