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Mixing Studies and Various Therapeutics

From Leslie Chaparro: We recently had a patient who had a mixing study ordered but who had recently taken tranexamic acid [TXA]. We exclude patients that have been on anticoagulants but have never really considered drugs that encourage clotting. How would this affect the patient’s mixing study? How do we keep up with all the new drugs and protocols and how do they affect coagulation results?

Hello, Leslie Chaparro, and thank you for your question. I’m attaching an open-access article; Gosselin RC, Marlar RA. Preanalytical variables in coagulation testing: setting the stage for accurate results. Semin Thromb Hemost 2019;45:433–48. The article provides some information about TXA. I will speculate, from the “data-free zone,” that TXA, which is an antifibrinolytic, has little effect on PT and PTT-based clot-based assays and that its half-life of two hours implies that we can proceed with testing after a four-hour wait.

The Gosselin/Marlar article provides fresh information about assay and specimen management in all of the current antithrombotic and anti-hemorrhagic therapeutics, but watch this space, as we will solicit opinions from several of our participants.

Comments (1)
Anticoagulant Therapy
Emmanuel Favaloro, PhD
Jul 15, 2023 6:55pm

Leslie Chaparro asks 2 questions. The first is “how would TXA affect a patient’s mixing study?”, and the second “how do we keep up with all the new drugs and protocols and how do they affect coagulation results?” In regards to the first question: I have not systematically investigated this, but I suspect TXA will affect (i.e., shorten) the aPTT where a prolonged aPTT is due to increased to increased fibrinolysis; however, I would not expect a generalized decrease in aPTT for all patients given TXA. I would suspect a lower influence on PT, but again would not be surprised to see a shortening in PT in a patient with increased fibrinolysis. In regards to mixing studies, the outcome will depend on whether TXA has affected the initial patient-based aPTT (/PT). Whether mixing studies have any value in patients on TXA, I will leave to others to address. In general, mixing studies have little value in patients on anticoagulant therapy, unless the aim is to pinpoint the type of anticoagulant therapy on board. That is, in an unconscious patient with prolonged coagulation tests, mixing studies may contribute to identification of an anticoagulant effect, and what the anticoagulant may be – thereby influencing management should there be a need to neutralize that effect (e.g., corrections upon mixing may suggest warfarin therapy, non corrections to thrombin time mixes may suggest heparin or dabigatran, which can be differentiated by anti-Xa or thrombin inhibitor testing, etc). Then targeted neutralization strategies may be applied. In regards to question 2, the only way to do this is to keep up with the literature or to ask the experts, using such tools as Fritsma Factor! This is a good time to plug my Test of the Month entry in AJH in 2020 (PubMed ID: 31674066: 488. Favaloro EJ. Coagulation mixing studies: utility, algorithmic strategies and limitations for lupus anticoagulant testing or follow up of abnormal coagulation tests. Am J Hematol. 2020 Jan;95(1):117-128. doi: 10.1002/ajh.25669). Another useful paper: Favaloro EJ, Lippi G. Laboratory testing in the era of direct or non-vitamin k antagonist oral anticoagulants: a practical guide to measuring their activity and avoiding diagnostic errors. Semin Thromb Hemost. 2015 Mar;41(2):208-27. doi: 10.1055/s-0035-1546827. PubMed PMID: 25703514.

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