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.
Category: Mixing Studies
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.
I pose this question to see what others are doing in this scenario and what literature there is to support your practice. We commonly get mixing study requests in which the PT or PTT are just minimally out of our normal range, such as 0.1 seconds outside for PT. Is this 0.1 second enough to do the mixing study or is there a buffer such as one second for PT and slightly more for PTTs in which although it is outside the normal range, that a mixing study could be not done? I don’t recall ever seeing one of these minimally prolonged PT/PTT turn out to be an inhibitor on followup. I would appreciate your feedback. Thanks. Bruce King, M.D.
From Ali Sadeghi-Khomami: Hi George, I read Dave McGlasson’s paper with great interest. In brief, his case had the following results:
|PTT 2 h 37°C incubation||>200s|
|Platelet neutralization (PNP)||Positive|
|Kaolin clotting time (KCT)||>200s|
- The article didn’t mention anything about a prolonged PT mix but just PTT have done that way.
- The PNP positive, could be a false positive due to factor V release from platelets.
- Later follow up: DRVVT screen and confirm both positive
- Staclot-LA negative, no data provided other than result on your site.
Yesterday, January 21, 2014, I posted “Incubated PT Mixing Studies?” in response to Lori Pinelli, and mentioned a patient Dave McGlasson worked up who had a Keflex-induced anti-factor V. The post attracted a comment from my colleague at Precision BioLogic Inc, Ali Sadeghi-Khomami, PhD, and just a few moments ago I added a comment emailed to me by Chris Ferrell at University of Washington Harborview. Both comments are insightful and provocative. As they say on TVLand, “BUT WAIT, THERE’S MORE!”
From Lori Pinelli, Glens Falls Hospital: Hello George. Our current prothrombin time (PT) mixing time procedure only includes running the initial 1:1 mix along with the patient and the normal pooled plasma (NPP). Twice in the past year, I have been asked to perform an incubated PT mix in addition to the initial analysis. Both patients had normal activated partial thromboplastin times (aPTTs, PTTs) and elevated PTs. They were both factor VII deficient and corrected upon addition of NPP. I was asked to perform the incubated mix to rule out an inhibitor. Are there time/heat dependent Factor VII inhibitors? Should I be routinely performing the incubated mix for PT correction studies? Thank you!
From Kathleen Tobertga: Hello, We are having problems between sites with the results of our 2 hour normal pooled plasma (NPP) control (unmixed) for our mixing studies. Our site (the main lab) is getting an increased value for the PTT around 40 s, which we have researched and seems to be elevated due to heat labile factors being destroyed. The other site is getting normal results for their 2 hour incubated NPP control (~32 secs). We are trying everything to figure out what is going on short of actually going over there and performing the testing ourselves. We are both using the same company for the pooled plasma, they are thawing at 37°C, we at room temp. Tommorow we will be trying to replicate each other’s thawing techinque to see if that is the variable. What I’d like to know, because I could only find it in one resource, are we correct about the heat labile factors and that the 2 hour incubated control should be increased, and do you have any place I can go to find documentation? Would be much appreciated. Thank you.