From “Danagah” (originally posted February 23, 2012):
Hi, George, have you seen the situation when, in the 1:1 immediate mix of a partial thromboplastin time (PTT) mixing study, the PTT is longer than the patient’s initial PTT? The patient does not appear to be on heparin (data to follow):
Patient PTT: 39.0 sec
Normal pool: 30.9 sec
1:1 immediate mix: 41.0 sec
Patient PT: 18.0 sec
Normal pool: 13.8 sec
1:1 immediate mix: 15.1 sec
Your expertise is greatly welcomed! Thank you.
Thank you for your question, and yes, there is an anecdotal phenomenon called “lupus anticoagulant cofactor” that is sometimes associated with a PTT mix that is actually prolonged beyond the prolongation of the patient plasma alone. I’ve found one publication documenting the LA cofactor, McGlasson DL, Higgs J. Presence of a lupus anticoagulant without the usual associated clinical conditions. Clin Lab Sci 1992;5:141–2. In this article the prolongation was evident when using a kaolin-based PTT reagent but disappeared when using an elagic acid-based reagent. I’ve not heard about this happening in a PT-based mixing study, however, so I’d like to hear from others if they have seen this. Geo.
I would concur with George; I would assess the sample for LA
I would concur with George; I would assess the sample for LA activity. This ‘LA cofactor’ phenomena is perhaps not as uncommon as might be otherwise appreciated, and it may be APTT reagent dependent. Only the APTT mix was greater than the patient APTT in this case. The PT mix showed partial correction. Could this be a mixed cause? Maybe liver disease as well, for example. I would recommend the following references for further reading (some are in press, but will be published in the next month or so):
Favaloro EJ, Bonar R, Zebeljan D, Kershaw G, Marsden K. Laboratory investigation of Lupus Anticoagulants: mixing studies are sometimes required. Journal of Thrombosis and Haemostasis. 2010; 8: 282831
Bonar R, Favaloro EJ, Zebeljan D, Rosenfeld D, Kershaw G, Mohammed S, Marsden K, Hertzberg M. Evaluating laboratory approaches to the identification of lupus anticoagulants: A diagnostic challenge from the RCPA Haematology QAP. Pathology, 2012; in press (PubMed PMID: 22183703)
Tripodi A, Pengo V. More on: laboratory investigation of lupus anticoagulants: mixing studies are sometimes required. J Thromb Haemost. 2011 Oct;9(10):2126-7.
Tripodi A. To Mix or Not to Mix in Lupus Anticoagulant Testing? That is the Question. Semin Thromb Hemost, 2012; 38: in press.