This arrived Wednesday from Mr. Peter Clement, MLS Student at Brigham Young University in Provo, Utah:
I am currently studying to become a Medical Laboratory Scientist. My professor is Dr. Shauna Anderson at BYU. I asked today if she had ever visited a website called Fritsma Factor, to which she replied yes and she added that she knows you. I have one question but before I just wanted to say that I have enjoyed using your site through three grueling weeks of coag that I’m almost done experiencing this Friday.
My question for you is whether or not there is a way to distinguish between high molecular weight kininogen (HMWK, Fitzgerald) factor and factor XII deficiencies without using assays? Apparently, according to old school methods you could differentiate prekallikrein (PK, Fletcher) deficiency by incubating for a longer period with kaolin and you can differentiate factor XI deficiency because it’s associated with bleeding tendency. However, all my research indicates that assays and perhaps family history are the only ways to differentiate HMWK from XII deficiency. Also, have they found anything that indicates why people with factor XII deficiency do not experience bleeding tendency?
Hello, Peter, and thank you for your question. Please send my greetings to Dr. Anderson, a friend and colleague whom I’ve know for a long time. I’d love to come to Utah and visit you and Dr. Anderson’s program some time, perhaps we could make it during ski season!
The only way to distinguish HMWK factor deficiency from factor XII deficiency is by a factor assay, and I know of only one source for HMWK-deficient plasma, Hyphen BioMed, distributed in North America by Aniara, Inc. You can get PK-deficient plasma from Precision BioLogic, Inc. and George King Bio-Medical, Inc, however, as you suggest, you can detect PK deficiency by incubating plasma with kaolin for 10-15 minutes. The PTT is prolonged before incubation but corrects to normal as PK becomes activated.
There is little clinical motivation for distinguishing HMWK deficiency from factor XII deficiency, as both are mere in vitro contact factors (same as PK) that have no in vivo procoagulant function, though they may be involved in fibrinolysis. That is why people with deficiencies have no bleeding tendency.
Peter, I hope you finished strong in coagulation, we could use some fresh new experts. I also wish you success as you start on your immunohematology course. Feel free to send blood bank questions to my wife, Margaret G. Fritsma, [email protected] if you need help.
Following a thorough negative workup for all ot
Following a thorough negative workup for all other possibilities (including a corrected standard mixing study) I use prekallikrein (PK, Fletcher) deficient and high molecular weight kininogen (HMWK, Fitzgerald) deficient plasma to mix with my patient. I do a 1/1 mix with each deficient plasma. The one that does not correct the patient confirms the deficiency.
I have had past success with extending the aPTT activation to 10 minutes using ellagic acid for PK. This does not work with IL Synthasil. Synthasil is colloidal silica and the aPTT results have been spuriously high, ranging from 90 to 170 seconds, same sample. This is typical with this reagent but I don’t know why. I would like to try a longer activation time, maybe 20 minutes, or a different activator.
When I mixed it the correction was complete and unequivocal- 32 seconds with either HMWK def or normal pool. I recently had two patients whose mix confirmed PK deficiency and mixing them together also did not correct, a nice reassurance.
Thank you (and Precision BioLogic, PBI) for this interesting site!