Interpreting mixing studies—prolonged PT / PTT

Learn how to use mixing studies to pinpoint the cause of prolonged PT (prothrombin time) or prolonged PTT (partial thromboplastin time) and investigate bleeding in patients with normal PT / PTT. By the end of this video from our Hematology and Coagulation Essentials course, you'll know when to order a mixing study, as well as how to interpret the results. Once you've mastered this, you'll know which tests need to be ordered next.

Demystify hematology and coagulation with our fascinating Hematology and Coagulation Essentials course! Hematological and coagulation disorders can be difficult to diagnose. By the end of this course, you'll be able to confidently assess the most important diagnostic aspects of hematology and coagulation and shine during your next night on call. Never again will you wonder what a prolonged PTT really means, how to differentiate between a factor deficiency and an inhibitor, or what tests to order next.

[00:00:00] Let us consider a patient who is undergoing a screen for coagulation tests. Most often this would include a complete blood count looking for thrombocytopenia and PT / PTT. If either the PT or PTT are abnormal and prolonged, then the logical question is, is the abnormal test result due to a clotting factor deficiency or due to an inhibitor? The next test to order to

[00:00:30] answer this question is a mixing study. The basic principle is we will measure PT and PTT before mixing and twice afterward. The first one will be immediately after mixing and the second one will be anytime 30 minutes to 2 hours after mixing. The abnormal PT or PTT will correct, that is, normalizes or fail to correct, that is, does not normalize. I would like to quickly

[00:01:00] remind you of factors involved in the two different pathways for coagulation. PT measures the integrity of the extrinsic and the common pathway, whereas PTT measures the integrity of the intrinsic and the common pathway. If the PT is prolonged, we are looking at pathology involving the extrinsic and the common pathway. So, when the PT is prolonged, we are going to perform a PT mixing study and this will be done twice: once immediately

[00:01:30] and the second time 30 minutes to 2 hours after mixing. If the PT normalizes, we are dealing with a factor deficiency and the involved factors may be factors 1, 2, 5, 7, and 10. If the PT does not normalize, then most likely we're dealing with an inhibitor and the most common inhibitor involving the pathway for PT, is factor 5 inhibitor. Now, moving on to the PTT mixing study.

[00:02:00] This is done when the PTT is prolonged and just like the PT mixing study, it is done twice: once immediately and second time 30 minutes to 2 hours after mixing. If the PTT normalizes with mixing, then we are dealing with a factor deficiency, and the factors involved may be factors 8, 9, 11, and 12. If the PTT initially shortens and then prolongs, then we are most likely dealing with a factor

[00:02:30] 8 inhibitor. If the PTT does not normalize, we may be dealing with a factor 9 inhibitor or more commonly a lupus anticoagulant. If an individual has both PT and PTT prolonged, we may be dealing with deficiency of factors in the common pathway or deficiency of factors in both pathways. Examples of such conditions include liver disease,

[00:03:00] vitamin K deficiency or disseminated intravascular coagulation also known as DIC. Rarely, PT and PTT may both be prolonged due to inhibitors to factor 5 and factor 10. Other causes of prolonged PT and PTT include drugs such as heparin, direct thrombin inhibitors and warfarin or

[00:03:30] superwarfarin, which is also a rat poison. Heparin in therapeutic doses predominantly prolongs PTT but in supratherapeutic doses can prolong both PT and PTT. Warfarin in therapeutic doses predominantly prolongs PT but not PTT but again, in supratherapeutic doses is well known to prolong both PT and PTT. Direct thrombin inhibitors are

[00:04:00] monitored by PTT but is known to cause prolongation of both PT and PTT.