Test Details
Methodology
The assay consists of the measurement of the clotting time, in the presence of cephalin and activator, in a system in which all the factors are present and in excess except factor XII, which is derived from the sample being tested. Testing coagulation factor activities requires that three dilutions be assayed and analyzed to produce a single result.9,10 The slope of the line created by plotting measured factor concentration against sample dilution is evaluated to discern the presence of inhibitors giving rise to nonparallelism.10 (Moreover, samples producing results on initial dilution falling outside the analytic measurement range of the assay are tested at additional dilutions to produce reportable results.10
Result Turnaround Time
2 - 3 days
Turnaround time is defined as the usual number of days from the date of pickup of a specimen for testing to when the result is released to the ordering provider. In some cases, additional time should be allowed for additional confirmatory or additional reflex tests. Testing schedules may vary.
Use
This test is used to evaluate a prolonged aPTT and detect specific coagulation factor XII activity.6,7
Special Instructions
If the patient's hematocrit exceeds 55%, the volume of citrate in the collection tube must be adjusted. Refer to Coagulation Collection Procedures for directions.
Limitations
Direct Xa or thrombin inhibitor therapy may cause factitiously low results.
Custom Additional Information
Factor XII, along with prekallikrein and high molecular weight kininogen, make up the contact activation system. These factors are necessary for clot formation in the activated partial thromboplastin (aPTT). In the test tube, factor XII is activated by contact with negatively-charged surfaces;8 however, deficiencies of these factors have no hemorrhagic consequence because physiologic clotting is activated by alternate paths that bypass the contact system.6,7
Factor XII is an 80 kilodalton single-chain proenzyme that is synthesized in the liver. Factor XII's plasma concentration is 30 mg/mL and half-life is about 50 hours. Factor XII deficiency is usually inherited in an autosomal recessive manner and heterozygous deficiency is relatively common, affecting somewhere between 1.5% and 3% of the population.6 In fact, mild factor XII deficiency is the most common cause of extended aPTT in the nonbleeding patient in the absence of lupus anticoagulant.6 Factor XII deficiency should be suspected whenever a patient has a normal protime (PT) and an extended aPTT and no history of bleeding. Factor XII levels are moderately diminished in heterozygous individuals with levels ranging between 20% and 60% of normal.7 Homozygous individuals typically have levels <1%.6 Severe factor XII deficiency is characterized by aPTT that can be longer than 100 seconds.7 Typically, there is correction with a normal plasma mixing study.
Factor XII can be affected, either increased and decreased, in a number of conditions including septicemia, coronary artery disease, pharmacological thrombolysis, inflammatory bowel disease, pregnancy, lactic acidosis, hemodialysis and angioedema.6,8 Decreased factor XII levels can be seen in liver disease and renal disease.6
A number of investigators have reported that congenital factor XII deficiency may be associated with an increased incidence of venous thrombosis;8 however, a recent consensus conference of the College of American Pathologists on diagnostic issues in thrombophilia found no evidence to support hypercoagulability in patients homozygously deficient for factor XII or any of the other contact factors.8
Specimen Requirements
Specimen
Plasma, frozen
Volume
1 mL
Container
Blue-top (sodium citrate) tube
Collection Instructions
Blood should be collected in a blue-top tube containing 3.2% buffered sodium citrate.1 Evacuated collection tubes must be filled to completion to ensure a proper blood-to-anticoagulant ratio.2,3 The sample should be mixed immediately by gentle inversion at least six times to ensure adequate mixing of the anticoagulant with the blood. A discard tube is not required prior to collection of coagulation samples unless the sample is collected using a winged (butterfly) collection system. With a winged blood collection set a discard tube should be drawn first to account for the dead space of the tubing and prevent under-filling of the evacuated tube.4,5 When noncitrate tubes are collected for other tests, collect sterile and nonadditive (red-top) tubes prior to citrate (blue-top) tubes. Any tube containing an alternative anticoagulant should be collected after the blue-top tube. Gel-barrier tubes and serum tubes with clot initiators should also be collected after the citrate tubes.
Please print and use the Volume Guide for Coagulation Testing to ensure proper draw volume.
Stability Requirements
| Temperature | Period |
|---|---|
| Frozen | 28 days |
| Freeze/thaw cycles | Stable x3 |
Reference Range
| Age | Range |
| 1 d | 43–80% |
| 3 d | 14–80% |
| 1 to 11 m | 20–135% |
| 1 to 5 y | 36–135% |
| 6 to 10 y | 26–137% |
| 11 to 16 y | 14–117% |
| >16 y | 51–168% |
Storage Instructions
Freeze.
Patient Preparation
Ideally, the patient should not be on anticoagulant therapy. Avoid warfarin (Coumadin®) therapy for two weeks prior to the test and heparin, direct Xa and thrombin inhibitor therapies for about three days prior to testing. Do not draw from an arm with a heparin lock or heparinized catheter.
Causes for Rejection
Severe hemolysis; improper labeling; clotted specimen; specimen diluted with IV fluids; samples thawed in transit; improper sample type; sample out of stability
References
Maas C, Renné T. Coagulation factor XII in thrombosis and inflammation. Blood. 2018 Apr 26;131(17):1903-1909. PubMed 29483100
STA® – Deficient XII Instructions For Use (IFU) [package insert]. February 2018.
Footnotes
LOINC® Map
| Order Code | Order Code Name | Order Loinc | Result Code | Result Code Name | UofM | Result LOINC |
|---|---|---|---|---|---|---|
| 086322 | Factor XII Activity | 3232-6 | 086322 | Factor XII Activity | % | 3232-6 |
| Order Code | 086322 | |||||
| Order Code Name | Factor XII Activity | |||||
| Order Loinc | 3232-6 | |||||
| Result Code | 086322 | |||||
| Result Code Name | Factor XII Activity | |||||
| UofM | % | |||||
| Result LOINC | 3232-6 |