| A B C D E F G H I J K L M N O P Q R S T U V W X Y Z # |
ACTIVATED PROTEIN C RESISTANCE
Message"Do not draw from an arm with a heparin lock or heparinized catheter
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.
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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.
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Test Code
117762
Alias/See Also
APCR
CPT Codes
85307
Preferred Specimen
Plasma 2 mL
Minimum Volume
1 mL
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 evacutated 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. To avoid delays in turnaround time when requesting multiple tests on frozen samples, please submit separate frozen specimens for each test requested.
Please print and use the Volume Guide for Coagulation Testing to ensure proper draw volume.
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Please print and use the Volume Guide for Coagulation Testing to ensure proper draw volume.
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Transport Container
"Blue-top (sodium citrate) tube
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Transport Temperature
Frozen
Specimen Stability
Freeze
Reject Criteria (Eg, hemolysis? Lipemia? Thaw/Other?)
"Gross hemolysis; clotted specimen; frozen specimen thawed in transit; tubes <90% full; improper labeling; specimen collected in tube other than 3.2% citrate
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Methodology
"This assay measures the effect of adding aPC on the activated partial thromboplastin time (aPTT) of the patient sample.8,9 An aPTT is performed twice, once with and again without added aPC. The ratio of the two clotting times is reported. The patient sample is diluted with factor V-deficient plasma. This serves to correct for any factor deficiencies in the patient sample and allows the test to be used for patients on oral anticoagulants. The reaction mixture also contains a heparin neutralizer to allow this test to be performed on patients receiving heparin therapy. "
Limitations
"This assay detects thrombotic risk factors other than factor VLeiden. This test should not be performed on individuals with extended baseline aPTT values due to the presence of lupus anticoagulants.6 This test should not be used for patients receiving thrombin inhibitors such as hirudin and argatroban.6 In some cases, this test will fail to distinguish individuals who are heterozygous for the factor VLeiden mutation from normals.7 Genetic testing may be required to distinguish between heterozygous and homozygous factor VLeiden mutation.7 Elevated factor VIII levels, as can be seen in acute phase reaction, can normalize the aPTT and effectively reduce the anticoagulant effect of aPC.7 Abnormal results can also be seen in pregnancy, especially during the third trimester, due to decreased levels of protein S and increased levels of factors V and VIII.7
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Reference Range
"2.0-4.0
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Clinical Significance
"Screening test for the factor VLeiden gene mutation and other causes of activated protein C resistance
Activated protein C (aPC), in a complex with protein S, inactivates procoagulant factors Va and VIIIa by proteolytic cleavage at specific arginine residues.7,10,11 This serves to control coagulation and limit the extent of thrombus formation. The functionality of the aPC inhibitory system in a given individual can be assessed through an in vitro clotting assay. Addition of aPC to a patient's plasma serves to extend the activated partial thromboplastin time (aPTT) for individuals who are sensitive to aPC. Individuals are considered to be aPC resistant when addition of aPC fails to extend the time to clot formation in this assay.
More than 95% of cases of aPC resistance are caused by a specific polymorphism in the factor V gene that is referred to as factor VLeiden.8 This single point mutation results in a substitution of glutamine for arginine at amino acid number 506 of factor V. Arginine number 506 is an aPC cleavage site of normal factor V, making factor VLeiden resistant to inactivation by aPC. Heterozygous factor VLeiden mutation occurs in 3% to 7% of persons of Northern European descent. However, this mutation is essentially absent in Asian, African, and Mediterranean populations.8 Individuals with heterozygous factor VLeiden have a three- to tenfold increased risk of thrombosis.8 The risk of thrombosis is approximately 80-fold increased in individuals who are homozygous for factor VLeiden.8 The incidence of factor VLeiden in unselected individuals experiencing their first venous thrombosis or pulmonary embolism is approximately 20%. In patients with a family history of thrombophilia, the likelihood of factor VLeiden being the cause reaches as high as 50%.8 Risk of thrombosis is further increased if the factor VLeiden mutation is accompanied by other prothrombotic conditions (ie, antithrombin, protein C or protein S deficiency, prothrombin G20210, pregnancy, oral contraceptive usage, prolonged immobilization, or surgery).
While factor VLeiden is, by far, the most common genetic cause of aPC resistance, other polymorphisms can produce this condition.9 aPC resistance can occur due to an elevated factor VIII level, in itself a risk factor for thrombosis.9 Factor VCambridge, a very rare mutation at another arginine residue of factor V, can produce aPC resistance.7,8 The HR2 haplotype, also referred to as A4070G mutation, is another rarely observed genetic cause of aPC resistance
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Activated protein C (aPC), in a complex with protein S, inactivates procoagulant factors Va and VIIIa by proteolytic cleavage at specific arginine residues.7,10,11 This serves to control coagulation and limit the extent of thrombus formation. The functionality of the aPC inhibitory system in a given individual can be assessed through an in vitro clotting assay. Addition of aPC to a patient's plasma serves to extend the activated partial thromboplastin time (aPTT) for individuals who are sensitive to aPC. Individuals are considered to be aPC resistant when addition of aPC fails to extend the time to clot formation in this assay.
More than 95% of cases of aPC resistance are caused by a specific polymorphism in the factor V gene that is referred to as factor VLeiden.8 This single point mutation results in a substitution of glutamine for arginine at amino acid number 506 of factor V. Arginine number 506 is an aPC cleavage site of normal factor V, making factor VLeiden resistant to inactivation by aPC. Heterozygous factor VLeiden mutation occurs in 3% to 7% of persons of Northern European descent. However, this mutation is essentially absent in Asian, African, and Mediterranean populations.8 Individuals with heterozygous factor VLeiden have a three- to tenfold increased risk of thrombosis.8 The risk of thrombosis is approximately 80-fold increased in individuals who are homozygous for factor VLeiden.8 The incidence of factor VLeiden in unselected individuals experiencing their first venous thrombosis or pulmonary embolism is approximately 20%. In patients with a family history of thrombophilia, the likelihood of factor VLeiden being the cause reaches as high as 50%.8 Risk of thrombosis is further increased if the factor VLeiden mutation is accompanied by other prothrombotic conditions (ie, antithrombin, protein C or protein S deficiency, prothrombin G20210, pregnancy, oral contraceptive usage, prolonged immobilization, or surgery).
While factor VLeiden is, by far, the most common genetic cause of aPC resistance, other polymorphisms can produce this condition.9 aPC resistance can occur due to an elevated factor VIII level, in itself a risk factor for thrombosis.9 Factor VCambridge, a very rare mutation at another arginine residue of factor V, can produce aPC resistance.7,8 The HR2 haplotype, also referred to as A4070G mutation, is another rarely observed genetic cause of aPC resistance
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