Assistant professor Cincinnati Children's Hospital Cincinnati, Ohio, United States
Background: Coagulation mixing study can help distinguish the etiology of a coagulopathy. One of the challenges in the interpretation of the results is due to the increasing use of direct oral anticoagulants (DOACs) which the inhibitory pattern to PT and PTT can vary in individual patients.
Aims: In this retrospective study, we sought to assess the effects of DOAC and other factors on PT/PTT mixing studies.
Methods: We reviewed more than 1000 mixing studies performed in the last 5 years in our laboratory that serve mostly adults in a large metropolitan area. About 300 cases were excluded from analysis due to a lack of associated clinical information. At our laboratory, mixing study is only performed when initial PT/PTT is prolonged. The PTT mixing study is performed at 0-minute and after 60-minute incubation at 37oC. The presence of interfering factors was confirmed with additional laboratory testing, medication records, and medical history.
Results: All cases were separated into several groups according to correction patterns. (Table) As expected, most prolonged PT samples (93%) were corrected by mixing while 36 cases showed incomplete correction. Half of these 36 cases were due to DOAC use and 5 cases were due to factor V (FV) inhibitor. Another rare pattern is the prolongation of PTT mixing result after incubation, which is considered a characteristic of a specific factor inhibitor, most commonly, FVIII inhibitor. Only 12 out of 46 cases with PTTmix prolongation were confirmed as FVIII inhibitor and both heparin treatment and strong lupus anticoagulant (LA) also contributed to 12 cases. Nine cases were due to DOAC use. Among 309 cases with prolonged PTT, 295 (95%) samples showed incomplete correction after mixing with more than half were associated with concurrent positive LA.
Conclusion(s): Anticoagulant treatment and strong LA are the major causes of rare correction patterns of PT/PTT mixing studies.
