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: Mixing Studies
This is from friend and colleague, Dean Willett, Instrumentation Laboratory:
Hi, George; A few points to consider…
There are two potential sources of interference here: biochemical and optical. Much like hemolysis, if the sample contains biochemical interference, results will be affected regardless of detection method. In the absence of any data it’s not clear if this drug introduces such a biochemical interference.
Read more »
From my friend Ali Sadeghi-Khomami, PhD, Precision Biologic Inc: Eltrombopag is a diazo derived compound
that acts like pH indicators, i. e., it changes colour at different concentrations of hydronium ions. Thus it is expected that it interferes with chromogenic assays such as bilirubin assay, especially when assay calibration will not match the colour of the testing sample.
This week George posts a new Quick Question to learn how we define PTT mixing study correction. Here is how the question will look:
When performing PTT mixing studies using normal control plasma (NP), what criterion do you use to define correction?
a. Mix result within 10% of NP result
b. Mix result within 5 seconds of NP result
c. Mix result within reference interval
d. Mix result within 5 seconds of reference interval mean
e. Other: Please post or email to firstname.lastname@example.org
There are more answers to this question than can efficiently fit into a multiple choice format, so please feel free to both vote in the right-hand column and respond in the comments section below with your approach, including your rationale and references. We will compile your responses and compare them with relevant comments from past Fritsma Factor entries. Thank you.
From Joyce Low: We have a patient with a prolonged prothrombin time (PT) and normal partial thromboplastin time (APTT, PTT). He bled, but factor levels were all normal. He’s an 84 year old man here for pacemaker insertion. PT was 19s (Neoplastine; reference interval 11–15s ), PTT 31s (Actin FS RI 25–35s), thrombin time, fibrinogen, and platelets normal. Patient developed a hematoma and infection at pacemaker insertion site. Pacemaker subsequently removed with bleeding that required 3 fresh frozen plasma twice.
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 Gabor Varadi, MD, Albert Einstein Cancer Center: Dear George, I would like to discuss with you a nose bleeding case. The patient is a 55 yo female with history of hepatitis C-induced chronic liver disease, alcohol and cocaine abuse who came to us with left nostril bleeding following finger trauma (nose picking). She does not have a history of previous bleeding.