Abstract
Introduction: Clot-based assays are employed to estimate coagulation factor activity in clinical pathology laboratories. These assays are PT- or aPTT-based and utilize dilutions of the patient's plasma in factor-deficient plasma. The curves of activity for each dilution follow a parallelism or non-parallelism pattern and the latter is typically seen in the presence of Lupus Anticoagulant (LA). Identification of this pattern is critical to avoid misdiagnosis of factor deficiency in patients who actually have an inhibitor. Materials and Methods: We observed low Factor XI (FXI) levels in patients with LA, while other factors were not affected. In order to determine the reason(s) why FXI levels are sensitive to LA, we collected 34 plasma samples from patients with dRVVT confirm ratio > 1.2, and estimated FVIII and FXI levels. FXI activity was also estimated with Dade ® Actin ® FS, a reagent that is not sensitive to the LA. The coefficient of variance (CV) for both FXI and FVIII levels were compared. To estimate the effects of heparin, plasma was spiked (0.1-1.0 IU/ML) and tested in the PTT, FXI, and FVIII assays. We tested with Dade ® Actin ® FS 4 known normal patients, 3 known FXI deficient patients, 20 known plasma positive for LA, and 10 with heparin. All assays were performed on a Siemens CS-5100 analyzer. Results: The results show that FXI is highly sensitive to LA, with non-parallelism and high CV, not observed with FVIII activity. As expected, FXI levels were not affected when LA-insensitive Dade ® Actin ® FS was used. Heparin (0.3-0.7 IU/ML) also showed non-parallelism in FXI activity, but not for FVIII. Only the highest dose of heparin (1.0 IU/ML) affected FVIII levels. Notably, the sensitivity of FXI activity to LA and heparin was explained by a few dilutions of the patient's plasma (5X) in the FXI assay, compared to other coagulation factors (20X). Of note, less diluted plasma is required for FXI activity because relatively higher levels of FXI is required to sustain and produce clot in the FXI-deficient plasma. Conclusion: This simple, yet not recognized explanation based on a literature search, is helpful to increase awareness of this analytical variable. It is also important to avoid misdiagnosis of FXI deficiency in patients with LA.
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