From Michele L. Drejka, Lead Technologist, Barnabas Health, Newark, NJ:
Hi George, Sorry to be redundant, but I posted this in ‘Comments,’ however I actually need an answer to my question below, so I am repeating here: Regarding prolonged activation times-I’m getting frustrated. I had more success with playing with this 15 years ago! However, this is what our lab does for prekallikrein (PK, Fletcher) and high molecular weight kininogen (HMWK, HK, Fitzgerald) deficiencies. First we do a silica-based partial thromboplastin time (PTT) mixing study with incubation. When it corrects without prolonging and all other factors are normal we go to a specific PTT mix using known PK-deficient and then HMWK-deficient plasma. When we find correction with one and non-correction (bingo!) with the other mix then we know which deficiency we have. Do you see any flaws in this rational? P.S. We do not quantify these two factors because of maintenance on assays that would be rarely used.
Hi, Michele, thanks for re-posting your question, and no, I find no flaws in your approach. Most of our participants know that the three contact factors are factor XII (Hageman), PK, and HMWK, and that deficiencies of any of these three are not associated with bleeding disorders. In the latest edition of Kitchens CS, Kessler CM, and Konkle BA. Consultative Hemostasis and Thrombosis. Elsevier, 2013 (just out), Escobar MA and Roberts HR, in chapter 5 give the incidence of congenital deficiency as factor XII and PK as unknown, and HMWK as very rare (less than 1 in 1,000,000). In my experience, factor XII deficiency is relatively common, though one only occasionally encounters PK, and especially HMWK deficiencies. In fact, I note that neither Precision BioLogic Inc nor George King Bio-medical, Inc. offer a HMWK-deficient plasma, so I’m curious about your source.
There is a “poor-man’s” approach to PK identification, detailed (by Cindy Johns) in the 1982 textbook Laboratory Evaluation of Coagulation, by the late Dr. Douglas Triplett. When a PTT using silica, Celite, or kaolin, but not ellagic acid activator is prolonged, incubate the reagent and plasma mixture for 10 minutes instead of 3 and repeat. If the PTT is corrected to within the reference interval, the deficiency is PK. Triplett wrote that PK deficiency is seen in newborns, and acquired PK deficiency is seen in liver disease, and references Hattersley PG, Hayse D: The effect of increased contact activation time on the APTT. Am J Clin Pathol 1976;66:479.