Factor XII (Hageman Factor) Test: Collection, Method, Clinical Relevance

What is Factor XII (Hageman Factor)?

Factor XII Test, also known as Hageman Factor or Factor XIIa, is a glycoprotein synthesized in the liver that plays a role in the intrinsic coagulation pathway and the activation of other biochemical systems like fibrinolysis and complement.

Patient Preparation

Avoid Coumadin® (warfarin) for 2 weeks before testing
Avoid heparin for 2 days before the test

Specimen and Container

Specimen: Plasma
Container: Blue top tube (sodium citrate)

Collection Protocol

If collecting multiple samples, draw coagulation studies last. For coag-only tests:

Draw 1–2 mL into a separate Vacutainer®, discard it
Then draw the coagulation test sample
This prevents contamination with tissue thromboplastins

Storage Instructions

Keep the specimen refrigerated
Deliver to the laboratory within 2 hours

Sample Rejection Criteria

Hemolyzed sample
Underfilled tube
Sample received more than 2 hours post-collection

Special Instructions

This is a rarely performed test. Contact the specialized coagulation laboratory in advance to schedule or arrange referral testing.

Reference Range

Normal: 50% to 150%
Homozygous deficiency: <1%
Heterozygous deficiency: 15% to 80%

Use

This test is used to document the absence or deficiency of Factor XII, often for patients with abnormal APTT but no bleeding tendency.

Limitations

Results may be altered if the patient is on anticoagulants
Delays in processing beyond 2 hours may affect test accuracy

Methodology

Modified activated partial thromboplastin time (APTT) assay
Uses known Factor XII–deficient substrate
Results interpreted from a normal plasma dilution curve

Biological and Clinical Insights

Factor XII is involved in the contact activation system alongside prekallikrein and high molecular weight kininogen (HMWK). It initiates several cascades including:

Fibrinolysis (activates plasminogen)
Complement activation (activates C1)
Bradykinin production (via HMWK)

Factor XII is a single-chain glycoprotein that becomes active when converted by kallikrein into a two-chain enzyme. The active site (serine) resides in the light chain, while the heavy chain aids in surface binding.

Although inherited as an autosomal recessive disorder, rare autosomal dominant cases have been observed. Both sexes are equally affected. Despite prolonged APTT, patients typically do not exhibit bleeding symptoms due to alternate coagulation pathways.

Clinical Observations and Risks

Prolonged APTT and whole blood clotting time in homozygous deficiency
Normal PT, thrombin time, and bleeding time
Rare but possible thromboembolic complications due to impaired fibrinolysis
Extended euglobulin clot lysis time

Structural Variants and Interactions

Factor XII Bern is a known variant with enzymatic activity impaired in its light chain. Eosinophil components such as eosinophil cationic protein and peroxidase may inhibit Hageman factor activation in vitro.

References

Jacobs et al., “Laboratory Test Handbook,” Lexi-Comp Inc, 1994
Braulke I. et al., “Factor XII Deficiency in Women With Habitual Abortion”, Fertil Steril, 1993
Mammen EF, “Contact Factor Abnormalities,” Semin Thromb Hemost, 1983
McDonough RJ & Nelson CL, “Clinical Implications of Factor XII Deficiency,” Oral Surg Oral Med Oral Pathol, 1989