Thread by @RubenVanPaemel

Let's give this #tweetorial (#hematorial?) thing a spin.

5 year old boy is referred after preoperative blood work. aPTT is ⬆️ (45, ULN = 38). PT & all other labs are normal. No bleeding symptoms. No medications, no recent infections. Normal physical exam.

What would you do?

The only really bad answer is D. The others can all be motivated. We did C. A could be, but surgery was already planned before.

But before moving on, let’s first go back to one of the horrors of med school, the dreaded coagulation cascade:

This model is great to show what happens in a test tube. aPTT tests the intrinsic coagulation cascade (VIII/IX/XI/XII). PT tests the extrinsic part (mainly VII).

DDX of an elongated aPTT is broad (meds, infection, liver disease, DIC, von Willebrand, hemophilia). But the patient is doing fine, without bleeding & other symptoms.

F. XII activity was repeatedly ⬇️ 30% (70-120). Other clotting factors were normal.

So, our patient seems to have a F. XII, or Hageman factor deficiency (named after the first patient in whom this factor was identified: John Hageman in the 1950s).

Is this a problem?

F. XII deficiency is kind of bizarre. It’s inherited autosomal recessive. But, does not seem to result in ⬆️bleeding, even if very low (1%) and during major surgery. Why not?

(Note: recombinant F. XII for substitution does not exist)

In vitro, contact with a negatively charged surface (i.e. glass and kaolin, used in aPTT assays) converts F. XII to F.XIIa starting the intrinsic cascade (see above). In vivo, F. XII does not seem to be essential for hemostasis.

This is in sharp contrast to the next clotting factor in the cascade (F. XI ~ hemophilia C). The reason why F. XII is dispensable in vivo is still not well understood, even 60 years after its discovery.

F. XI & others downstream of F. XII *DO* result in bleeding symptoms. XI does not initiate but is essential for propagation and maintenance of clotting. After generation of thrombin, there is a + loop with platelets and XI/XIa working together to form more thrombin, bypassing XII

Even though he was missing a clotting factor, John Hageman curiously died in 1968 after a pulmonary embolism. Since then, some evidence points to the association of F. XII⬇️ with an increased risk of thromboembolism and recurrent abortions, but evidence is low.

This first #tweetorial was inspired by @DrKanaris, @VPplenarysesh, @AdamRodmanMD. If you like this, read theirs. More reading about F. XII: doi.org/10.1182/blood-… & doi.org/10.1111/jth.13…
Disclaimer: this is for education only, not medical advice. All case details are fictive.

Did you learn something?