Utility and Interpretation of Coagulation Mixing Studies

Coagulation testing is essential for the diagnosis and management of a variety of hemophilia, thrombophilia, and complicated coagulopathies. This is often used prior to surgery, or as a follow-up investigation for patients being scrutinized for bleeding diathesis, or to monitor the anticoagulant therapy. When the results are abnormal, a mixing study is often the initial reflexive test that can provide valuable information to conclude the assessment, or help guide further investigations. If the mixing “corrects” the test results, a factor deficiency would be suspected. Otherwise, the presence of an inhibitor would be more likely. However, defining “correction” remains difficult and controversial. There are several available methods to determine whether a result is corrected. Each method has its own advantages and limitations. It is noteworthy that although a complete correction can be interpreted as factor deficiency, a partial or incomplete correction does not rule out the coexistence of factor deficiency and the presence of a coagulation inhibitor. Hence, caution should be taken in interpreting mixing study results for patients who are taking direct-acting oral anticoagulants. Ideally, mixing study results are interpreted in correlation with the patient’s clinical history, including bleeding or thrombosis history, and the use of anticoagulants. This review aimed to evaluate the methods used in interpreting coagulation mixing studies and to discuss their respective advantages and limitations.