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Prolonged PT, No Correction, Normal PTT

An intriguing case from “Annamaria09″

Hi, we have a very interesting case, a young man with an unexplained high prothrombin time (PT) that does not correct when mixed with pooled normal plasma, however his partial thromboplastin time (APTT) is normal. He also has an unexplained low hemoglobin and elevated platelet count. He is not on coumadin or any other drugs. What’s your opinion on this and what other tests should we do? Lupus anticoagulant, and a total factor study workup? including factor V Leiden? One thing I forgot to mention, we did notice that when we ran the APTT for the 1:1 mix, it became elevated from baseline, that we cannot explain.

The patient was not bleeding and has had no history of such occurrences, we did get one preliminary result back: his fibrinogen is >800 mg/dL. Could his increased platelet count also be a factor? His doctor also told us that he has some enlarged lymph nodes as well.

Thank you, Annamaria. The textbook would have you start with coagulation factor VII, which, if deficient, would prolong the PT but not the PTT. You may want to try a factor VII activity level, though I admit that a factor VII deficiency would be associated with bleeding and would correct in a mixing study.

Another possibility is a mild liver disorder producing dysfunctional prothrombin, factor V, or factor X. Typically, as these are part of the common pathway, the PTT should also prolong, however it may be the PT reagent is more sensitive to the abnormality than the PTT. Follow up with assays of II, V, and X.

Back when we were using bovine thrombin to make surgical fibrin glue, patients would develop anti-prothrombin and anti-factor V antibodies that would cross-react in some test platforms and not others because of their bovine specificity. Fibrin glue is now produced using human thrombin, and this phenomenon is going away, however it is possible if the patient had had surgery with the use of fibrin glue several years ago. It is worth asking the question.

A fourth possibility is a lupus anticoagulant specific for prothrombin. This has been reported, though these LAs are associated with thrombocytopenia, not thrombocytosis, and with bleeding (not the usual thrombosis). For this idea, you need an assay for the prothrombin-specific LA, see Corgenix Anti-phospholipid Antibody Flyer.

And finally, Dave McGlasson, who often gives me a hand with these complex cases, suggests checking out the patient’s fibrinogen by running a thrombin time and a reptilase time. He is thinking the patient could have a dysfibrinogenemia, which could be inherited or secondary to early liver disease.  Reptilase times are not done routinely, and I just posted a new audio PowerPoint on Thrombin Time and reptilase times in case you are interested.

Well, you can tell, when I cast about and suggest five possible scenarios, I don’t really have a good answer. I’m hoping one of the smart people who regularly look over the site can come up with an answer that fits all the circumstances!

Comments (2)
May 12, 2011 3:25am

Could it be simply an extremely elevated VIII (acute phase r
Could it be simply an extremely elevated VIII (acute phase reactant along with high fibrinogen) making the PTT normal but actually a positive lupus not correcting in the mixing study?

May 5, 2011 8:00am

Relative to this case, first ask, is it is a real coagulatio
Relative to this case, first ask, is it is a real coagulation problem or PT interference? I’ve had personal experience with Endoxan prolonging only the PT. What you may do with the PT but not the PTT is to dilute in Owren Koller buffer. It has to be linear on a x:1/x paper or using percentage calibration if you have one. If you check the factors as you dilute the plasma 1:20 it is quite the best to test the interference. This is not a better answer but if it helps…

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