Prolonged PTT in FXII Deficiency

From Maria Grana, Baptist Health Center:

Hello, we recently had a patient with very high partial thromboplastin time (aPTT, PTT) resu;ts, anywhere from 115 to >200 seconds. The mixing study indicated a factor deficiency. Factor assays performed (IX, XI) were within normal limits, FVIII was elevated (>200) and Factor XII was 48%. It did not appear that FXII was low enough to warrant such a high aPTT. Is this a true statement? How low does the factor XII have to be to produce such a high aPTT? Thanks!

Hello Maria. According to Halbmayer MW, Haushofer A, Schon R, et al, The prevalence of moderate and severe FXII deficiency among the normal population: evaluation of the incidence of FXII deficiency among 300 healthy blood donors. Thromb Haemost 1994;71:68–72, factor XII deficiency is inherited as an autosomal recessive trait. The factor is absent from the plasma of homozygotes and is present at 20–60% in heterozygotes. Heterozygous factor XII deficiency is present in 2% of normal people.

From laboratory experience, I’ve found the PTT to be relatively sensitive to moderate factor XII deficiency, owing to its presence at the top of the intrinsic coagulation mechanism. Sensitivity varies with the composition of the PTT reagent, particularly the type of activator used. I wasn’t surprised to learn your patient’s PTT was prolonged, although >200 seconds for 48% factor XII level seems extreme. Regrettably, I’ve not found anything in coag literature to confirm my experience. Experts agree that the absence of factor XII profoundly prolongs PTT results, however little is published about the PTT when factor XII levels are around 50%.

I’m currently contacting some experts who have published on this topic, and hope to have more definitive information within a few days. Meanwhile, I invite our participants to share their experience.