Factor XI Assay 

Updated: Jan 17, 2014
  • Author: Bishnu Prasad Devkota, MD, MHI, FRCS(Edin), FRCS(Glasg), FACP; Chief Editor: Eric B Staros, MD  more...
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Reference Range

The so-called contact factors include factor XI, factor XII, high-molecular-weight kininogen (HK), and prekallikrein (PK). Factor XI is synthesized in the liver and megakaryocytes and is an 80-kd zymogen precursor of a serine protease. It circulates in complex with the nonenzymatic cofactor HK [1] and has a mean plasma half-life of about 52 hours.

The reference range for factor XI is between 60% and 120% of normal values. [2]

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Interpretation

Deficiency of factor XI is a congenital condition that is inherited in an autosomal-recessive fashion. Marked decreases in factor XI are indicative of a mild bleeding diathesis.

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Collection and Panels

Collection procedure and panels for factor XI are as follows:

  • Specimen: Blood
  • Container: Blue-top vacuum tube
  • Collection method: Routine venipuncture
  • Packing: To comply with Occupational Safety and Health Administration (OSHA) safety standards, samples must be sent in a leakproof sealed container labeled with a biohazard sticker
  • Panels: Quantitative functional assays of coagulation factors
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Background

Description

The so-called contact factors include factor XI, factor XII, high-molecular-weight kininogen (HK), and prekallikrein (PK). Factor XI is synthesized in the liver and megakaryocytes and is an 80-kd zymogen precursor of a serine protease. It circulates in complex with the nonenzymatic cofactor HK [1] and has a mean plasma half-life of about 52 hours. The gene for factor XI is located on chromosome 4. [3]

There are multiple mechanisms by which factor XI can be activated. It can be activated in vitro by activated factor XII (XIIa). It can be activated by thrombin in the fluid phase and on charged surfaces even without the presence of other contact factors [4, 5] ; it can also be activated by thrombin on the surface of activated platelets, a pathway that is the most likely mechanism of in vivo activation in vivo during hemostasis. [6] In a mouse model, factor XI appears to play a greater role in thrombosis than in hemostasis. [7]

Activation of factor IX by activated factor XI (XIa) is calcium-dependent but requires no other cofactors. Binding of factor XIa to activated platelets localizes it to the site of clot formation, as well as protects it from plasma protease inhibitors. [1] Factor XI enhances generation of thrombin at the platelet surface.

In mice, knockout of the gene for factor XI does not lead to death in utero. [8] In humans, however, factor XI deficiencies can give rise to bleeding tendencies, [9] which, though significant, are not as severe as those seen in hemophilia A or hemophilia B. This finding reflects the important role factor XI plays in hemostasis.

Indications/applications

Factor XI is warranted when a deficiency of factor XI is suspected.

Considerations

Several plasma protease inhibitors that circulate in high concentrations are capable of inhibiting factor XIa. Of these, the ones with the strongest affinity for this factor are (in order) the Serpin protease nexin 1, C1-esterase inhibitor, antithrombin, protease inhibitor, and plasmin inhibitor. [1] Protease nexin 2, a tightly binding Kunitz-type factor XIa inhibitor, is also present in platelets. [1, 10]

The partial thromboplastin time (PTT) is prolonged, but not the prothrombin time (PT; if the level is markedly decreased).

The following factors may limit the accuracy of the test [2] :

  • Partial clotting of specimens resulting from poor mixing of anticoagulant (3:2 sodium citrate as per manufacturer’s blue topped tube)
  • Overfilling or underfilling of test tubes, altering the blood-to-anticoagulant ratio (9:1)
  • Improper storage of plasma
  • Contamination with heparin or, if indwelling catheters are in place, dilution of the collected sample
  • Analytical errors (eg, lipemic, icteric, or hemolyzed plasma), which may interfere with photoelectric measuring instruments
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