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- Activated Partial Thromboplastin Time (aPTT)
The aPTT is sensitive to deficiency or inhibition of factors in the intrinsic pathway. These include the contact factors; high molecular weight kininogen (HMWK), prekallikrein, and factor XII along with procoagulant factors XI, IX, VIII. The aPTT is less sensitive to deficiencies of X, V, prothrombin, and fibrinogen.1 Nonspecific, lupus-type anticoagulants can also extend the aPTT, but the more sensitive aPTT-LA test should be used to screen for this condition.
The aPTT-LA is a more sensitive screening test for identifying lupus anticoagulants in patients with a history of thrombosis. The aPTT may not be extended in individual factor deficiencies unless the levels drop below 15% to 45% depending on the factor.6 Less significant individual factor deficiencies in combination (multiple factor deficiency) can extend the aPTT.6 The aPTT is more sensitive to intrinsic pathway factor deficiencies than common pathway factor deficiencies.6 Factor VIII elevations, as can occur due to acute phase reactions, can normalize a mildly extended aPTT result.6
A large number of conditions can complicate the use of the aPTT in monitoring UFH therapy,7 The College of American Pathologists (CAP) divided these factors into three groups.7 The first group of complicating factors encompasses those that affect the bioavailability of heparin. Aging, obesity, changes in heparin binding proteins, hepatic disease, renal disease, and heparin resistance fall under this heading. The second group of complicating factors includes those that alter the aPTT dose response to heparin.
Increased factor VIII or fibrinogen levels, decreased antithrombin levels, or a mild reduction in multiple factors (as might be seen in the early stages of a consumptive coagulopathy or in oral anticoagulant therapy) are examples of this type of complicating factor. Lastly, those factors that tend to cause a prolonged aPTT in the absence of heparin therapy should be considered. Lupus anticoagulants or deficiency in contact factors can produce an extended baseline aPTT. In all of these cases, the heparin anti-Xa assay may be more appropriate for monitoring heparin therapy. The aPTT should not be used for therapeutic monitoring of low molecular weight heparin or danaparoid.7,8
The aPTT reagent consisting of silica mixed with synthetic phospholipid is mixed with the patient plasma. The silica provides a negatively-charged particulate surface for the activation of the contact pathway of coagulation. Calcium chloride is then added to the sample/reagent mixture to initiate clot formation. The time to clot formation is measured photo-optically.
0 to 3 d
4 d to 6 m
7 m to 17 y
The aPTT is often ordered, along with the prothrombin time, to diagnose the cause of patient bleeding or as part of a presurgical screen to rule out coagulation defects.9-11 The aPTT can be prolonged when the activities of any of the factors of the intrinsic pathway are significantly diminished. Deficiencies or inhibition of high molecular weight kininogen (HMWK), prekallikrein, or factors XII, XI, IX, and VIII can result in an extended aPTT with a normal protime (PT) since these factors are not part of the extrinsic pathway. Significant deficiencies of factors that are common to both the intrinsic and extrinsic pathways (factors X, V, prothrombin, or fibrinogen) can extend both the aPTT and PT.
An extended aPTT can be seen in acquired deficiencies of factors II, IX, and X that result from vitamin K deficiency or the use of anticoagulants that block vitamin K-dependent production of procoagulant factors. These conditions also affect the level of factor VII, an extrinsic pathway factor. Since factor VII has a short half-life relative to the vitamin K-dependent factors of the intrinsic pathway, nutritional or therapeutic vitamin K-dependent factor deficiency can sometimes result in an extended PT with a normal aPTT. Consumption coagulopathies, such as disseminated intravascular coagulation (DIC), can produce an extended aPTT due to depletion of intrinsic factors. The aPTT can also be extended in conditions that reduce the production of procoagulant factors (ie, severe liver disease or malnutrition). Inhibitors, both factor specific and nonspecific, can also prolong the aPTT. A description of the many potential causes of an extended aPTT is described in more detail in the online Coagulation Appendix: Lupus Anticoagulants.
Unfractionated heparin is commonly used to limit fibrin clot formation in individuals with increased risk of venous or arterial thrombosis.12 Overdosing with heparin can increase the risk of hemorrhage and inadequate dosing decreases the efficacy of anticoagulation. Heparin works as an anticoagulant by enhancing the ability of plasma antithrombin to bind and inactivate the serine proteases XII, XI, IX, X, and thrombin. Therapeutic monitoring with the aPTT is commonly used because of the wide interindividual variation in response to this therapy; however, this application of the aPTT test can be less than optimal in a number of clinical circumstances (see Limitations).
Whole blood or plasma
4.5 mL, 2.7 mL, 1.8 mL
90% of full draw
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. 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.
Specimens are stable at room temperature for 24 hours. If testing cannot be completed within 24 hours, specimens should be centrifuged for at least 10 minutes at 1500xg. Plasma should then be transferred to a LabCorp PP transpak frozen purple tube with screw cap (LabCorp N° 49482). Freeze immediately and maintain frozen until tested. Refer to Coagulation Collection Procedures for directions.
Requirements for patients receiving heparin are different: If testing cannot be performed within one hour of collection, frozen plasma must be submitted. Specimens should be centrifuged for at least 15 minutes at 1500xg to produce platelet-poor plasma and the plasma quick frozen and maintained in this condition until tested.
Causes for Rejection
Gross hemolysis; clotted specimen; frozen specimen thawed in transit; tubes <90% full; improper labeling; specimen collected in tube other than 3.2% citrate
This test is for screening purposes only; it should not be used for therapeutic unfractionated heparin monitoring. Please refer to test Heparin Anti-Xa . 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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