Factor XII Activity
Evaluate a prolonged aPTT and detect specific coagulation factor XII activity.
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 surface however, deficiencies of these factors have no hemorrhagic consequence because physiologic clotting is activated by alternate paths that bypass the contact system.
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. In fact, mild factor XII deficiency is the most common cause of extended aPTT in the nonbleeding patient in the absence of lupus anticoagulant. 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. Homozygous individuals typically have levels <1%.6 Severe factor XII deficiency is characterized by aPTT that can be longer than 100 seconds. 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. Decreased factor XII levels can be seen in liver disease and renal disease.
A number of investigators have reported that congenital factor XII deficiency may be associated with an increased incidence of venous thrombosis 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.
Blue-top (sodium citrate) tube
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.
Blood should be collected in a blue-top tube containing 3.2% buffered sodium citrate. Evacuated collection tubes must be filled to completion to ensure a proper blood-to-anticoagulant ratio. 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. 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.
Severe hemolysis; improper labeling; clotted specimen; specimen diluted with IV fluids; samples thawed in transit; improper sample type; sample out of stability