Evaluation of Activated Partial Thromboplastin Time Mixing Studies Using Several Methods

Context.— A prolonged activated partial thromboplastin time (APTT), a vital screening test for coagulation, can be due to deficiencies in coagulation factors and the existence of factor inhibitors or antiphospholipid antibodies. APTT mixing studies are being optimized to help find the cause. Objective.— To optimize APTT mixing studies, we evaluated existing standards and explored when and how to combine 1:1 and 4:1 mixing. Design.— Patients with a prolonged APTT but otherwise normal prothrombin time and thrombin time were enrolled in our hospital from January 1, 2018, to December 31, 2019. All samples were subjected to 1:1 mixing studies, while 134 were subjected to 4:1. Results.— A total of 251 samples were involved, including 116 with factor deficiencies, 75 with FVIII inhibitors, and 60 with antiphospholipid antibodies. A Rosner index less than 11% or an extended incubation time of more than 3 seconds was better than other existing standards in differentiating factor deficiencies from inhibitors and in differentiating time-dependent inhibitors from time-independent inhibitors, but the approach presented here improves upon those. For the best diagnostic accuracy, samples with a Rosner index between 5.0% and 9.1% need a 4:1 mixing study, while others need 1:1. A combination of Rosner index and percent-extended incubation time-P seemed to offer objective and effective criteria for interpreting the results. Conclusions.— APTT mixing studies had overall good sensitivity and specificity in differentiating factor deficiencies from inhibitors, or time-dependent from time-independent inhibitors. The combination of 1:1 and 4:1 mixing studies can improve the diagnostic ability compared with 1:1 alone.