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Shortened PTT and Mixing Studies

From “plovejoy:”

Is there a reason one might perform a partial thromboplastin time (PTT) mixing study on a patient whose initial PTT result is short (slightly below the reference range)? Since a short PTT time would appear to indicate there isn’t a factor deficiency or a circulating anticoagulant, might there be another reason? I couldn’t find anything in the literature.

Hello, and thank you for your question. No, nothing can be gained by performing a standard mixing study on a shortened PTT. Mixing studies are designed to detect inhibitors or factor deficiencies that prolong the PTT, and are unlikely to provide any information for a shortened PTT.

We’ve always assumed that short prothrombin times (PTs) and PTTs were the consequence of a specimen management error, however I draw your attention to a 2010 article, Lippi G, Salvagno GL, Ippolito L, Franchini M, Favaloro EJ. Shortened activated partial thromboplastin time: causes and management. Blood Coagul Fibrinolysis 2010;21:459-63. that speculates on the possible clinical and physiological causes. While a mixing study doesn’t help, there may be an argument for factor assays that detect, for instance, elevated factor VIII, which could be associated with thrombophilia. Geo.

Comments (1)
Jan 24, 2011 12:30pm

Good morning P and George. This appears to be a simple ques
Good morning P and George. This appears to be a simple question on the surface, but as one drills deeper, the complexity of our coagulation system becomes evident. Certainly the doctor may want to pursue the Factor VIII track for thrombophilia and I would add to the discussion Factor XI (more on that later).

It is entirely possible a mixing study would have been ordered based on information the patient provided to the physician such as “easy bruising” or “abnormal clotting.” The physician would order a mixing study to differentiate a factor deficiency from a lupus anticoagulant (LA). The patient in question most likely does not have a factor deficiency (depending on the sensitivity of the reagents and instruments being used), but a LA has not been ruled out because of a (shortened) normal PTT. We see a significant percentage of LA patients who have a normal PTT and normal PTT mixing studies.

In addition, we see patients whom we suspect have a LA that test normal for PTT, mixing studies and all of our tests for LA (DRVVT, STA-Clot LA and Dilute PT Index). In these patients, we will usually find a marginally decreased Factor XI, measuring around the lower edge of the normal reference range and all other PTT based factors are normal.

As in all things coag, be prepared for the unexpected. While one would suspect that all LAs would prolong the PTT and give a positive mixing study, it does not always work that way. If your patient is suspected of having a LA, the work-up should not stop at a normal PTT or a normal mixing study.

Herb Crown
St. Louis University Hospital Coag Reference Lab

Thanks, Herb; one could also reflex to anti-beta-2-glycoprotein 1 and anti-cardiolipin antibody. Geo.

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