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Mixing Studies on Minimally Prolonged PTs and PTTs

I pose this question to see what others are doing in this scenario and what literature there is to support your practice. We commonly get mixing study requests in which the PT or PTT are just minimally out of our normal range, such as 0.1 seconds outside for PT. Is this 0.1 second enough to do the mixing study or is there a buffer such as one second for PT and slightly more for PTTs in which although it is outside the normal range, that a mixing study could be not done? I don’t recall ever seeing one of these minimally prolonged PT/PTT turn out to be an inhibitor on followup. I would appreciate your feedback. Thanks.Bruce King, M.D.

Hello, Dr. King, and thank you for the question. This was the last day of the very successful Thrombosis and Hemostasis Summit of North America in Chicago, and I took the opportunity to pose your question to colleagues Larry Brace, PhD of Edward Hospital, Naperville, IL, and Larry Smith, PhD, of Memorial Sloan-Kettering in New York. Both agreed with the policy in our local institution, that any result outside the normal range may be subjected to a mixing study if there is an indication. Both would reflex a prolonged PT or PTT to a mixing study in consultation with the physician managing the case, and would only proceed if the physician saw a diagnostic need. In most instances, the physician realizes that a second or two beyond the reference interval limit is within the routine variability of the assay and would not require follow-up, however it may be the mixing study provides an answer for a clinical question. Since the range for correction is narrow, I suggest that correction be defined on the basis of the pooled normal control used in mixing, and not the mean or limit of the reference interval. I hope this helps, and look forward to colleagues’ responses, which may include references.

Comments (3)
Mixing Studies
Aug 21, 2014 7:48am

We’ve replaced the mixing studies with a panel we call UPCOA
We’ve replaced the mixing studies with a panel we call UPCOAG (unexplained prolonged coag). Using the patient history to guide testing, we perform the minimum number of specific assays needed to explain why a screening test gives a prolonged result. Pretty much every sample submitted gets tested for LA as we see them co-exist with many other conditions. We always rule out anticoagulants either by chart history, heparin assay, TCT, etc and then work with the clinician to find the real answer (usually before an incubated mixing study could be completed).

Aug 8, 2014 1:04pm

We have also found that a mixing study on a PTT just slightl
We have also found that a mixing study on a PTT just slightly over our reference interval usually corrects. In our lab we will only do a mixing study on a PTT that is at least 10 seconds over the reference interval. We do not perform mixing studies on protimes anymore since the result was usually equivocal. We offer to perform factor assays in a prolonged protime.

Apr 14, 2014 1:22am

I have learned to never say never in hemostasis testing foll
I have learned to never say never in hemostasis testing follow-up, since I still get surprises. However, follow up of slightly prolonged coagulation test times are in the main likely to be fruitless. First, the normal range by definition only captures some 95% of the normal population (mean +/- 2SDs), meaning that most test results just above the upper normal limit will just reflect these ‘aberrant’ normals. Second, unless you strike the rare lupus inhibitor that shows extended APTT times on mixing, most mixing study algorithms will result in a ‘normal’ mixing test result simply because of the low range of difference; certainly this will be true if you define a normal mix as that which falls into the normal range, since even ‘inhibitor’ samples will generate such a interpretation if the patient result is just above the upper normal cut-off. A strongly recommended paper is: Kershaw G, Orellana D. Mixing tests: diagnostic aides in the investigation of prolonged prothrombin times and activated partial thromboplastin times. Semin Thromb Hemost. 2013 Apr;39(3):283-90.

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