Mixing Studies

I attended the Twelfth Annual Symposium on Bleeding and Thrombosis May 6 and 7 in Indianapolis. The meeting was sponsored by Midwest Coag Hemostasis and Thrombosis Laboratories and Esoterix, Inc. Laboratory Services and administered by Charles C. Miraglia, MD.

I learned several interesting things at the meeting, but would like to feature a series of discussions on the partial thromboplastin time (PTT) and PTT mixing studies led byRavindra (Ravi) Sarode, MD, UT Southwestern Medical Center, Dallas; Steve Kitchen, MD, Sheffield Haemophilia and Thrombosis Centre, UK, and Dorothy (Dot) Adcock-Funk, MD, Medical Director of Esoterix Coagulation.

Dr. Sarode began by asking whether every unexplained prolonged PTT should be followed with a mixing study. (“Unexplained” implies any PTT prolonged in the absence of unfractionated heparin therapy.) He mentioned first that the prothrombin time (PT) and PTT were never meant to assess bleeding risk in a non-bleeding (pre-op) patient, although they are routinely misused as admission screens. This was confirmed by data presented later by Dr. Kitchen. Dr. Sarode then used a series of case studies to illustrate situations where mixing studies were inconclusive and caused unnecessary delays, and others where studies were useful. He made the point that the clinical situation may indicate the need to bypass mixing studies and move right into patient treatment.

For instance, he presented a case of a PTT of 38 seconds (reference interval 25-35) that corrects to 33 seconds on immediate mixing. Surgery was delayed a week while the laboratory tracked down a transient lupus anticoagulant. Dr. Adcock commented later that there is little to be gained by performing mixing studies on a specimen with a PTT just a few seconds beyond normal.

Dr. Sarode emphasized that mixing study techniques are not standardized from lab to lab, use no controls, use no consistent definition for normal pooled plasma, placed insufficient emphasis on platelet free plasma, and are performed by every TDH (Tom, Dick, or Harry).

Based on these discussions, I’ve begun to post a series of quick questions about mixing studies, beginning this week by asking what criteria you use for correction Vs. non-correction. We will follow up with additional questions about mixing study practices. Meanwhile, I’d like to hear from you about your PTT mixing study practices.