Another brain teaser from Kim Kinney at Clarian in Indianapolis:

Hi George,

I am working on a case study for American Society for Clinical Laboratory Science (ASCLS). We had a patient who came in for a right hip replacement and ended up being < 1% high molecular weight kininogen (HMWK, Fitzgerald factor) and 58% prekallikrein (PK, Fletcher factor), also decreased. We had no previous coagulation data even though she had the left hip replaced seven years prior. Is there an association between HMWK/PK deficiency and thrombosis like there is with XII? I cannot find it in writing in any of my reference books. This lady has since developed DVTs in both legs and is on coumadin and Plavix. Funny though, there is no mention of the HMWK deficiency in her file. As always, thanks for your help. Kim.

Here is a question about HELLP from a colleague with heterozygous factor V Leiden mutation.

George: If you have not heard I had my baby, a healthy boy.  I had HELLP syndrome/preeclampsia.  Do you know of any studies that may link factor V Leiden to HELLP? Just curious.....

This is an interesting issue that we have encountered in our laboratory too. We have used a Kaolin based reagent with good success in some cases. I will be giving an oral presentation at the upcoming Mayo Testing Quality Conference about our experience using an alternative
activating reagent to perform factor assays in the presence of Lupus Anticoagulants.

Sincerely,
 

John P Barranco MT (ASCP)

Thank you, John. I look forward to attending your presentation at Mayo. Geo.
 

Janice Richardson asks, "Why does a low factor XII cause clotting?"

Factor XII was described in 1955 by Ratnoff and Colopy who recognized its deficiency in an American male, John Hageman. Factor XII deficiency causes a markedly prolonged activated partial thromboplastin time (APTT, PTT) but paradoxically does not associate with bleeding. Most of us know Mr. Hageman died of a pulmonary embolism after a hip fracture, implying the deficiency has no protective effect and could be prothrombotic. Factor XII is one of the contact factors, along with prekallikrein (PK, Fletcher factor), and high molecular weight kininogen (HMWK, Fitzgerald factor). Some include factor XI and a complement pathway control protein, C1 inhibitor (C1-INH), which binds factor XII.

More...

From Eric Creager at Diagnostica Stago:

I am curious why a strong lupus anticoagulant seems to target factor XI?. I have seen multiple cases of strong LA with a FXI assay as low as 10%. Serial dilutions sometimes show increasing FXI activity results with larger dilutions. Most recent case was a 44 YO male appearing with bleeding and a FXI of 8%. The DRVVT ratio was 1.7 ( <1.2 normal).
Is there a reason why XI becomes the target so often?

Thanks
 
Eric Creager
Central Region Support Coordinator
Diagnostica Stago Inc
Parsippany, NJ 07054

Good afternoon,  I have been referred to you to ask about Factor V.  After my sisters tested positive for this blood disorder I took the test for Factor V and was told that my count was 2.49.  My family physician is not familiar with this disorder.  I would like to know if this number means that I tested positive  for this condition, or am I negative?  What should my next step be?  Should I make an appointment with a hemotologist?  I would really appreciate your opinion, as I am told you are quite familiar with Factor V. Thank you so much for your time.  Sincerely, Jan Scott

I provide two lectures for UAB's Masters in Nurse Anesthesia (MNA) program. The first is  "Managing the Bleeding Patient" in which I give an overview of the coagulation system followed by a rundown of the acquired and congenital bleeding disorders and how the lab may contribute to their diagnosis and treatment.

The second lecture is "Thrombosis Risk Testing and Anticoagulant Therapy." From the second lecture, Ben Tomlin asks "What are the prevalences for each of the thrombotic risk factors?"

Here is a question from Carla Clem at Clarian in Indianapolis. Carla works with Kim Kinney and teaches with Bernadette (Bunny) Rodak for the Clarian/Indiana University Clinical Laboratory Science program.

Hi George,
I am Bunny's "partner in crime;" we team-teach in Heme at Clarian/IU. Would you please give us a kindergarten version of ADAMTS-13 with regard to principle and typical results in TTP?

Thanks, Carla

Hi, Carla. I’ll be glad to describe thrombotic thrombocytopenic purpura (TTP) and the role of von Willebrand factor (VWF)- cleaving protease (ADAMTS13). There is an excellent free public access review: Tsai H. Thrombotic thrombocytopenic purpura: A thrombotic disorder caused by ADAMTS13 deficiency. Hematol Oncol Clin North Am 2007; 21:1-25 that you can access for detail.

I've never understood why protein C and protein S immunoassay results are reduced in Warfarin therapy. Because Warfarin reduces gamma-carboxylation of protein C and protein S glutamic acid units, we expect there to be reduction in activity assays but it turns out that immunoassay results are also proportionally reduced.

Here is an interesting message about paraoxonase from colleague Dan Southern.

"Have you ever heard of paraoxonase? The article below, out of Cleveland Clinic, makes me want to be tested yesterday." "Cleveland Clinic Researchers Show Strong Relationship Between HDL-Associated Protein And Protection From Heart Disease Risk"

Findings Appear in Special Genetics in Medicine Issue Published by Journal of the American Medical Association on March 19.

Detailed description follows...