Here is another thought-provoking email from Dr. Jay Lozier at the NIH. I need some expert help with this one.
From Dr. Lozier: “I am in the position of hematology consultant who runs the coag lab. We see some interesting cases from time to time. I see a fair amount of storage pool deficiency that we diagnose on the basis of aggregations and electron micrographs to confirm.
“Just diagnosed a dysfibrinogenemia that manifests itself as an isolated prolonged prothrombin time (PT) that did not correct with a mix. Fibrinogen activity (Stago, Clauss method) was 87 mg/dL, but fibrinogen antigen was >400 mg/dL (Mancini radial immunodiffusion). Had not seen that presentation before; no bleeding.
Might be a good post/question to put out there: the PT that doesn’t correct with a mix…”
Jay Lozier, MD, PhD, FACP
NIH Clinical Center Department of Laboratory Medicine
Thank you, Dr. Lozier, and yes, this is a good question to put out there. Why should a dysfibrinogenemia fail to correct in a PT mixing study? I’m looking for an answer out there!
And while we are at it, let’s also go into more detail on typical aggregation patterns in storage pool deficiency, and what sorts of patients present this way. I’d like to see some real-life examples, as I hope they support the stuff we write in textbooks. Geo.
Hello Dr. Lozier and George. I agree, this is an interestin
Hello Dr. Lozier and George. I agree, this is an interesting one. There are a couple of things that come to mind, the first being to repeat this testing on a newly acquired specimen. If the repeat testing is the same as the original testing, then we are safe to say this is potentially a real issue.
Concerning the dysfibrinogenemia, I would like to see the fibrinogen antigen assay on further dilutions. I would run out the dilutions to the point that I have an actual number to work with rather than a “greater than”. (Since I have never performed this procedure I do not know what kind of dilutions it would take to do so.) I would also serially dilute the patients plasma and run the fibrinogen on the STAGO instrument. A reptilase time and thrombin time may also be helpful.
In my limited experience the only thing I have seen that causes the PT inhibitor screen to not correct is a Factor V inhibitor. There may be other causes, but that is the limit of my experience. I would like to see the Factor V activity and additionally a bovine thrombin time (the Stago uses human thrombin.)
More testing is needed and I am looking forward to seeing those results.
St. Louis University Hospital Coagulation Reference Laboratory