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Test Catalog

Test ID: APTSC    
Activated Partial Thromboplastin Time (APTT), Plasma

Useful For Suggests clinical disorders or settings where the test may be helpful

Screening for certain coagulation factor deficiencies and abnormalities (eg, factor VIII, IX, XI or XII)

 

Detecting coagulation inhibitors such as lupus anticoagulant, antiphospholipid antibodies, specific factor inhibitors, and nonspecific inhibitors

 

Evaluating a prolonged APTT test result to assist in differentiating coagulation factor deficiencies from coagulation inhibitors, especially when the activated partial thromboplastin time (APTT) mixing test results are combined with results of other coagulation tests and clinical information

 

Monitoring heparin (unfractionated) therapy

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The activated partial thromboplastin time (APTT) measures the integrity of the intrinsic (factors VIII, IX, XI and XII) and common (factors II, V, X, and I [fibrinogen]) pathway coagulation factors as well as contact factors, prekallikrein (PK) and high-molecular-weight kininogen (HMWK). The APTT assay depends on the phospholipid (a partial thromboplastin), contact activator (eg, silica), and ionic calcium supplied in the reagents.

 

A prolonged APTT may be caused by congenital or acquired coagulation factor deficiencies, anticoagulant effect such as heparin anticoagulation therapy, and inhibition due to lupus anticoagulants as well as other nonspecific coagulation inhibitors (eg, monoclonal immunoglobulins).

 

Although the APTT is commonly used as an initial test for detecting coagulation factor deficiencies, various reagents differ considerably in their sensitivity to deficiencies of coagulation factor proteins. The reagents are generally most sensitive to deficiencies of "contact factors" (XII, PK and HMWK) and factor XI, less sensitive to deficiencies of factors VIII and IX (the "antihemophilic factors"), and least sensitive to deficiencies of common procoagulant pathway factors (X, V, II, I). The APTT prolongs typically when the activities of factors XI and XII are below the hemostatically adequate level of 40% to 50%. Although factor XII deficiency does not cause bleeding, it is a relatively common cause of APTT prolongation. Nevertheless, an APTT may still be normal when the factor VIII level is as low as 25% to 35%; factor IX as low as 20% to 30%, as seen in some patients with mild hemophilia A or B, respectively a shortened APTT due to increased factor VIII activity secondary to inflammation, pregnancy, or estrogen use, or other conditions may masquerade deficiencies of other factors.

 

The APTT also has divergent sensitivity to nonspecific inhibitors of the intrinsic and common coagulation pathways, such as lupus anticoagulant (LAC) and specific coagulation factor inhibitors. LAC's are antibodies directed towards neoepitopes presented by complexes of phospholipid and proteins, such as prothrombin (factor II) or beta 2 glycoprotein I, instead of coagulation factors. They interfere with the in vitro phospholipid component of APTT assay, and result in a prolonged clotting time. Clinically, lupus anticoagulant represents an important marker of thrombotic tendency. In contrast, patients with specific coagulation inhibitors, such as factor VIII inhibitor antibodies, have a significant risk of hemorrhage and often require specific treatment for effective management.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Only orderable as part of a special coagulation profile or as a reflex. For more information see:

ALUPP / Lupus Anticoagulant Profile, Plasma

ALBLD / Bleeding Diathesis Profile, Limited, Plasma

AATHR / Thrombophilia Profile, Plasma

APROL / Prolonged Clot Time Profile, Plasma

ADIC / Disseminated Intravascular Coagulation/Intravascular Coagulation and Fibrinolysis (DIC/ICF) Profile, Plasma

 

25–37 seconds

The APTT may be 35% longer in full-term newborns that reach adult reference range by age 3 months and twice the adult upper limit in premature infants reaching adult reference range by age 6 months.

Interpretation Provides information to assist in interpretation of the test results

Prolongation of the activated partial thromboplastin time (APTT) can occur as a result of deficiency of 1 or more coagulation factors (acquired or congenital in origin), or the presence of an inhibitor of coagulation such as heparin, a lupus anticoagulant, a "nonspecific" inhibitor such as a monoclonal immunoglobulin, or a specific coagulation factor inhibitor.

 

The APTT mixing study, which uses equal volumes of patient and normal pool plasma, may be performed on specimens with a prolonged APTT to assist in differentiating coagulation factor deficiencies from coagulation inhibitors of all types.(1-4) Correction of the APTT mix to within the normal reference range usually indicates a coagulation factor deficiency (normal plasma in the mixture ensures at least 50% activity of all coagulation factors). If the prolonged APTT is due to an inhibitor (eg, specific coagulation factor inhibitor, lupus anticoagulant, heparin), the APTT mix typically fails to correct a prolonged APTT. However, the presence of a weak inhibitor may be missed by the APTT mixing study.

 

Accurate interpretation of both APTT and APTT mixing study results may often require additional testing. For example, the thrombin time (TT) test is helpful for identifying or excluding the presence of heparin, the platelet neutralization procedure (PNP, using a modified APTT method) for identifying or excluding lupus anticoagulant, the prothrombin time (PT) and dilute Russell's viper venom time (DRVVT) for further assessment of the common procoagulant pathway, and coagulation factor assays to detect and identify deficient or abnormal factors. These assays are available as components of reflexive and interpretive testing panels in the Special Coagulation Laboratory (eg, APROL / Prolonged Clot Time Profile).

 

The APTT test is frequently used to monitor therapy with unfractionated heparin (UFH). Since APTT reagents can vary greatly in their sensitivity to UFH, it is important to establish a relationship between APTT response and heparin concentration.(1) The therapeutic APTT range in seconds should correspond with a UFH concentration of 0.3 to 0.7 U/mL as assessed by a heparin assay (inhibition of factor Xa activity with detection by a chromogenic substrate [1]). We have established the therapeutic APTT range to be approximately 70 to 120 seconds.

 

Shortening of the APTT usually reflects either elevation of factor VIII activity secondary to acute or chronic illness or inflammation, or spurious results from suboptimal venipuncture, specimen collection or processing. A normal or shortened APTT result does not exclude a hemostatic defect; and specific clotting factor assays should be performed despite a normal APTT when there is clinical impression of bleeding diathesis.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

For diagnostic activated partial thromboplastin time (APTT) testing, other than heparin therapeutic monitoring, specimens should not have any residual heparin present.

 

Mild coagulation factor deficiency may not result in prolongation of the APTT. APTT testing will not detect all lupus anticoagulants or coagulation inhibitors.

 

Lipemic specimens may interfere with the instrument clot detection mechanism.

 

APTT mixing studies have no utility when the patient APTT is normal.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Olson JD, Arkin CF, Brandt JT, et al: Laboratory monitoring of heparin therapy. Arch Pathol Lab Med 1998;122:782-798

2. Miletich JP: Activated partial thromboplastin time. In Williams Hematology. Fifth edition. Edited by E Beutler, MA Lichtman, BA Coller, TJ Kipps. New York, McGraw-Hill, 1995, pp L85-86

3. Greaves M, Preston FE: Approach to the bleeding patient. In Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Fourth edition. Edited by RW Colman, J Hirsh, VJ Marder, et al: Philadelphia, JB Lippincott Co, 2001, pp 1197-1234

4. Kaczor, DA, Bickford NN, Triplett DA: Evaluation of different mixing study reagents and dilution effect in lupus anticoagulant testing. Am J Clin Pathol 1991;95:408-411

5. Brandt JT, Triplett DA, Alving B, Scharrer I: Criteria for the diagnosis of lupus anticoagulants: an update. Thromb Haemost 1995;74(5):1185-1190