On Thursday, May 21, 2009 at the University of Alabama at Birmingham Department of Pathology  I provided a lecture on the history of hemophilia therapy entitled "Hemophilia Therapy, Rasputin to Recombinants." Here is the lecture as a 6-per page PDF for the lecture participants or any Fritsma Factor members. Geo.

Here is a message from Col. More at Elmendorf in Alaska:

Hi, we have a pregnant mom, having a boy, who says her dad has hemophilia.  I'm waiting for more history on that.  In the meantime I looked for ways to test the mom.  I found that if you run factor VIII and IX antigen and activity levels, antigen levels in carriers should be two times the factor VIII activity levels.  Do you know of a PCR test or other genetic test?

Thanks, Lucia

LUCIA E. MORE, Lt Col, USAF, BSC
Laboratory Flight Commander
PACAF Laboratory Consultant
DSN  580-6511

A question from Bruce King at Lancaster General:

I was wondering about the practicality of adding a test for factor VIII inhibitors in our community hospital setting. Although we don't get many requests for it, it appears that when you get a request for a factor VIII inhibitor in a non-hemophilia patient, there is a significant degree of urgency in getting rapid results. Our current reference laboratory performing this test has a TAT of about a week which is less than ideal for a more urgent clinical need for this information. We currently do some more manual coagulation methods such as inhibitor screens with 50:50 mixes and incubation phases. Are there community hospitals doing this test and how did you go about setting it up and running it? Any assistance is most appreciated.

Here’s some detailed follow-up to Kelly Townsend’s question about the factor VIII inhibitor assay. First, a little detail on the assay, commonly called the Bethesda titer. This is adapted from Kitchen S, McCraw A: Diagnosis of Haemophilia and other Bleeding Disorders, A Laboratory Manual, 2000, prepared for the World Federation of Hemophilia Laboratory Sciences Committee, 1425 René Lévesque Boulevard West, Suite 1010 Montréal, Québec H3G 1T7 Canada.

Some questions about factor VIII inhibitors from Kelly Townsend at TriCore:

• When performing Factor VIII inhibitor testing, at what activity level do you either treat the specimen to inactivate patient factor VIII or not perform the assay?
• If you do treat the sample, exactly what do you do (what temp and how long)?
• Does your protocol differ if the patient has hemophilia and has an inhibitor because he’s been getting product versus a non-hemophilia patient with an acquired inhibitor?

Thanks for any advice you can give,

Kelly Townsend, MT(ASCP)SH
TriCore Reference Laboratories
Albuquerque, NM

A question about Ehlers-Danlos syndrome from Dr. John McClure:
I was asked by a hematology colleague about bleeding risk in an Ehlers-Danlos patient.  He was consulted for a preoperative assessment.  The patient has a "self-reported" history of bleeding but has undergone uneventful lap-chole and vaginal deliveries. My colleague is specifically asking about the PFA 100 to screen for platelet functional defects. I'm not sure how to direct him.  I predict that her risk is "pretty low" based on history.  I also guess that the bigger risk in these patients is vascular integrity which is largely beyond our control. Any thoughts on preoperative screening for these patients?  What test?  Worthwhile?  Thoughts on a plan B if surgery becomes problematic? Thanks, John McClure.

Here is a case sent by Ashli Jarrell, an articulation student in the University of Cincinnati online CLS program. I will leave the answer open for a few days to get your opinion:

Hi, George.

I have an interesting case: 26 YO female. History: nosebleeds since age 3; age 5 tonsillectomy with increased bleeding post-op; age 7 admitted to hospital for bruising and nosebleeds, lymphocytic leukemia negative; required transfusions after auto accident and labor. Began menstruation at age 12 with periods lasting three weeks. At times requires FFP to control bleeding. Family history: Mom and dad are living and well; brother and sister living with no bleeding problems. Lab results: PT 23 s; PTT >200 s; TT 21 s; fibrinogen 250 mg/dL; mixed PT 11 s; mixed PTT 28 s.

Please help!
Thanks, Ashli

Please select "comment" to respond. Geo.

Our coagulation lab specialists at UAB have noted anecdotally that long term bleeding is accompanied by elevated factor VIII activity levels. Have others seen this, and is there a reference documenting it? Geo.

Here is an interesting finding presented yesterday at the ASH meeting detailing apparent overuse of platelet concentrate:

Click Here for link to article

Here is a delightful message from my colleague Betty Ciesla at Morgan State University in Baltimore.

Hi George, I am trying to explain the Bethesda titer, which I find difficult. My students do too. I understand you make a 1:1 mix of patient plasma and control plasma, incubate, test using the PTT then you make a control mix? What is that and how does it fit in? And then what?

Also, how do we decide who is a low responder and high responder and how does that affect their treatment?

I have re-read your explanation in Rodak's 2nd edition millions of time but it is just not doing it for me. Please help. Betty Ciesla

Betty, please see my discussion below...