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Prekallikrein Assay

A question from Delphine in France about prekallikrein (PK, Fletcher factor) deficiency measurement:

is there a difference between the PTT with kaolin versus silica to measure PK deficiency? What is the impact of incubation time? It seems PTT with kaolin doesn’t work well to measure PK?

Hi, Delphine. I checked your question with Lynn Quarles of Diagnostica Stago-US, since Stago’s main office is in France. Lynn writes, “I checked with our advanced support group about this. We have a PTT reagent called CK-Prest, which works well with contact factors. It is kaolin-based, and the consensus from our group is that it works for PK, although we don’t know of instances where it is actually being used for this. I had a customer who did a PK deficiency screen using our PTT Automate (silica-based) and a 10-minute incubation time. Isn’t there also a chromogenic assay for prekallikrein?”

[Added by Lynn 10/31/09]: I have attached our CK Prest (Stago) package insert. I noticed that under the limitations section it states CK-Prest is usually insensitive to prekallikrein deficiencies. Therefore, despite the anecdotes from our group,  I recommend using PTT Automate for monitoring PK.

I also reviewed the old Triplett DA, Congenital coagulation factor deficiencies, Chapter 3 in Triplett DA, Laboratory Evaluation of Coagulation, ASCP Press, Chicago, 1982. Triplett writes that the PTT reagent may be formulated with either kaolin or Celite (silica), but not ellagic acid, which cannot detect PK deficiency.

Precision BioLogic provides a PK-deficient plasma for a PK activity assay. Their direction insert does not specify the type of PTT reagent. It may be that kaolin-based reagents are not used routinely because they do not function well in automated coagulometers.

To further expand upon Lynne’s answer, yes, diaPharma and Chromogenix provide a substrate for PK, factor XIa and factor XIIa, S-2302. In the US S-2303 is labeled “for research use only.”

Lynne is also correct about the incubation time, and in fact, PK incubation behavior may be exploited as a “poor-man’s” screen to distinguish from other contact factor deficiencies. If the PTT is prolonged and a PK deficiency is suspected, incubate the plasma with the PTT reagent for 10 to 60 minutes and repeat. The prolongation remains if factor XII or high molecular weight kininogen (HMWK, Fitzgerald factor) is deficient, but reverts to normal in PK deficiency because HMWK and XII slowly activate during incubation and bypass PK. This information is provided in Chapter 4 of our old textbook, Corriveau DM, Fritsma GA. Hemostasis and Thrombosis in the Clinical Laboratory. Lippincott, 1988.

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