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Combined IX and XII Deficiency?

From Dr. Jeanine WalengaLoyola 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.

Hi, Jeanine, and thank you. I speculate the PTT was prolonged by the XII, and not the IX deficiency, as most PTT reagents are calibrated to prolong at IX levels of 30–40%. Could the apparent IX deficiency actually reflect a mild XII deficiency in your reagent factor IX-deficient (depleted) plasma? It may be the reagent plasma was not validated for XII activity. I’d be inclined to suggest in the absence of bleeding symptoms a factor IX activity level of 64% does not imply a bleeding risk. However, I’m reaching out for help on this one, would like to be sure.

Got this note from Chris Ferrell (same day): Sorry George, I don’t have anything to add.  Those values would not be considered deficient with my ranges.

Comments (4)
Factor Assays
Vadim Kostousov
Sep 10, 2014 6:48am

How two mild factor deficiencies prolong APTT or PT was show
How two mild factor deficiencies prolong APTT or PT was shown in vitro by Burns ER et al. in 1993: “When plasma samples containing 50% activity of a single factor and 100% of all other factors were prepared by mixing the congenitally deficient plasma samples with the normal pool, the resulting mixtures had normal PT and APTT values. However, when two of these 50% factor-deficient plasmas were combined so that the mixture contained 75% activity of two coagulation factors and 100% of all other factors, the resulting PT and APTT were prolonged over the clotting times of either 50% factor-deficient plasma.”

Jeanine Walenga
Sep 9, 2014 1:56pm

Thanks for the quick responses. The factor assays were done
Thanks for the quick responses. The factor assays were done by a reference lab so I don’t have any more specific information. The chromogenic testing is a good idea for confirmation. I agree the bleeding risk is not high. Nice to have your support.

Dave McGlasson
Sep 9, 2014 4:39am

The deficiencies described are in the normal range in our fa
The deficiencies described are in the normal range in our facility. In the past I have done a number of evaluations of reagents from a number of companies. I would check for coagulation deficiencies in the factor deficient substrates. I once found a factor IX deficient substrate plasma that had very low levels of factor VIII also present. I would also be surprised by a factor XII deficiency of that level affecting a PTT assay. I once had a group of subjects receiving bone marrow transplants that had factor XII levels around 20% activity that the particular PTT reagent gave results in the normal range. Many companies don’t worry about the sensitivity of the factor deficiencies until they get below 30% activity. This sounds like an artifact more than a true clinical condition. I do like the idea of getting a chromogenic factor IX assay performed to see if this is really a true deficiency also.

Ali Sadeghi-khomami
Sep 8, 2014 7:16pm

Sometimes, multiple borderline factor levels could clinicall
Sometimes, multiple borderline factor levels could clinically manifest as a real factor deficient situation. In your case, running a chromogenic factor IX will tell us if factor XII deficiency caused an artifact in the factor IX clotting assay result or not. In the absence of real factor IX deficiency in this case, bleeding risk is not high because even real factor XII deficiency is not associated with excessive bleeding. I am curious to know about the PTT reagent used in your factor assays.

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