The stem of our June, 2017 Quick Question was, “In a PTT mixing study, the patient’s initial PTT is 67 s, RI 25–35. The PTT is repeated after mixing 1:1 with NP, and the new result is 63 s, NP 30 s. What do you do next?” This was a quiz question with a correct answer, rather than the usual survey question. The choices were:
A. Reflex to a lupus anticoagulant profile. 41 votes, 53%
B. Reflex to FVIII, FIX, and FXI activity assays, 7 votes, 9%
C. Make a new 1:1 mix, incubate 2 h at 37C and repeat, 29 votes, 37%
D. Report the presence of a specific inhibitor such as anti-FVIII, 2 votes, 3%
Susan Atkinson of Moncton, New Brunswick commented that the first step when you encounter an isolated prolonged PTT is to check for heparin with the thrombin time or chromogenic anti-Xa heparin assay. George left this important step out of the question, but let’s presume we’ve performed the TT and generated a normal result, indicating no heparin is present.
The correct answer is A, reflex to a lupus anticoagulant (LA) profile. Most LAs avidly neutralize PTT reagent phospholipids. The mix result of 63 seconds, normal plasma (NP) 30 seconds, is a “non-corrected” mixing study, indicating phosphoipid neutralization. This provides a presumptive diagnosis of LA and leads to a confirmatory LA profile.
Most practitioners use 10% above the normal plasma PTT value, in this case, 33 seconds, as the limit defining correction (see Mixing Study Correction Limits). Had the result of the 1:1 mix been 33 seconds or less, the result would be reported as “corrected.” In this case, the next step is incubating a new mix, as detailed in answer C. The incubation step is not necessary when the initial mix results in non-correction. The incubated mix is designed to detect specific inhibitors such as anti-FVIII, which are mostly IgG4 isotype immunoglobulins that bind their target epitope most avidly at 37C. Were a specific inhibitor suspected, for instance, if the patient experiences bleeding symptoms, if would be appropriate to reflex to factor assays, answer B.