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.
Category: Mixing Studies
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.
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!”