From Dr. Samir Patel: George, I have enjoyed reading the blog for many years now (since fellowship) and am wondering if you could shed some light on a patient I am working up. This is a 90 year old woman who was sent for evaluation after she developed a hematoma post cardiac catheterization (no need for transfusion, bleeding controlled with pressure). At that time she was noted to have a prolonged partial thromboplastin time (APTT, PTT) and so came for evaluation. I have done almost everything I can think of and still can not explain what is causing her prolonged PTT, and more importantly she is in need of repeat cardiac cath and likely valve repair surgery in the future. She is not on any medications that could be causing this for many months. Mixing studies suggest the presence of an inhibitor.
Category: Factor Assays
From Dr. Jeanine Walenga, Loyola University Medical Center: George, what could be the reason(s) for a 30 yo female patient having multiple
mild factor deficiencies of FIX (64%) and FXII (51%)? The activated partial thromboplastin time (APTT, PTT) was slightly prolonged but corrected with a mixing study. FVIII and FXI were normal. Patient does not have LA or anti-phospholipid antibodies. The best I came up with was that the deficiencies might be due to enhanced excretion from a nephrotic syndrome. Would the double factor deficiencies account for the slightly prolonged APTT? Does the patient have a bleeding risk if going for surgery? Thanks.
From Kelly Townsend, Tri-core Reference Laboratories, Albuquerque. Looking for opinions on what constitutes a “Laboratory Developed Test” in Coag. Obviously if the reagent kit is not FDA-cleared, it will be an LDT, but what about factor assays, etc where there is no real kit. What if you are using a kit with a different calibrator or control than the manufacturer sells/endorses? Having trouble coming up with a concise definition for LDT. Thanks, Kelly.
From Pam Owens: Hi George, good to see you at THSNA! (Thrombosis and Hemostasis Summit of North America). I am hearing more about how ineffective the 5M urea test is for factor XIII screening and am thinking we just need to stop doing the assay in our lab. I’ll need to convince our lab director. Are there any articles or published studies out there? I’m not having any luck looking on line.
Each year George enjoys the opportunity to teach in Dr. Elaine Keohane’s graduate course, CLSC 5124, Advanced Hemostasis at Rutgers University School of Health Related Professions. Our students are experienced medical laboratory scientists from all over the world, and they bring a wealth of practical knowledge. Dr. Keohane is teaching a section on platelet physiology this week, and the question came up, what is platelet factor 3? I’m old enough to know the answer, but I’d like to hear from our participants. In addition to defining PF3, also please report what coagulation laboratory assay we used to “diagnose” PF3 deficiency.
From Deborah Whetzel, Children’s Hospital of the King’s Daughters, Norfolk, VA: We’ve had a couple patients lately that demonstrated inhibition but their factor VIII results are within normal limits or even elevated. The result values differ 30–40% typically between dilutions but as they’re diluted more, the values go up to 300 or 400%. FVIII values that high seem really odd to me. We dilute to 1:160, as I’ve seen recommended, with results to that point continuing to get higher. Have you seen this occur and is there something that we should be doing? Thanks for your help.
From Kim Kinney, Indiana University Health, Hi George! We have a severe hemophiliac with an 8BU inhibitor receiving ReFacto. Factor assays are high, but dilutions dilute backward! 367, 238, then 183, then 167 causing a CV flag. We have seen this before, but have never heard an explanation for the “backward” dilution affect. Can you shed light? It does not happen on all treated hemophiliacs…is it the ReFacto? Thanks for the info!
From Manju Bala, St Christopher’s Hospital for Children. Need help with interpreting a coagulation dilemma. A child, 4 months old, post cardiac surgery, no meds, use of bovine thrombin during surgery with prolonged prothrombin time (PT), 29.9s; partial thromboplastin time (PTT, APTT),107.7s; and thrombin time (TT), 40.4s; no correction on mixing. FII, 25%; FV, 7%, increasing with dilution; FVIII, 129%; FIX, 39%; FX, 69% and FXI, 50%. The latter four factors, although normal appear to increase on dilution like an inhibitor. No evidence of bleeding, no evidence of thrombosis, liver function tests normal. Could this be due to an antibody to bovine thrombin or lupus anticoagulant? Testing is pending.