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The activated partial thromboplastin time (APTT) test reflects the activities of most of the coagulation factors, including factor XII and other "contact factors" (prekallikrein [PK] and high-molecular-weight kininogen [HMWK]) and factors XI, IX, and VIII in the intrinsic procoagulant pathway, as well as coagulation factors in the common procoagulant pathway that include factors X, V, II and fibrinogen (factor I). The APTT also depends on phospholipid (a partial thromboplastin) and ionic calcium, as well as an activator of the contact factors (eg, silica), but reflects neither the extrinsic procoagulant pathway that includes factor VII and tissue factor, nor the activity of factor XIII (fibrin stabilizing factor).
The APTT is variably sensitive to the presence of specific and nonspecific inhibitors of the intrinsic and common coagulation pathways, including lupus anticoagulants or antiphospholipid antibodies. Lupus anticoagulants may interfere with in vitro phospholipid-dependent coagulation tests, such as the APTT, and prolong the clotting time. Lupus anticoagulants are antibodies directed towards neoepitopes presented by complexes of phospholipid and proteins, such as prothrombin (factor II) or beta 2 glycoprotein I, but these antibodies do not specifically inhibit any of the coagulation factors. 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. Both types of disorders may have similar prolongation of the APTT.
Monitoring heparin therapy (unfractionated heparin)
Screening for certain coagulation factor deficiencies
Detection of coagulation inhibitors such as lupus anticoagulant, specific factor inhibitors, and nonspecific inhibitors
Since activated partial thromboplastin time (APTT) reagents can vary greatly in their sensitivity to unfractionated heparin (UFH), it is important for laboratories to establish a relationship between APTT response and heparin concentration. The therapeutic APTT range in seconds should correspond with an UFH concentration of 0.3 to 0.7 U/mL as assessed by heparin assay (inhibition of factor Xa activity with detection by a chromogenic substrate). In our laboratory, we have found the therapeutic APTT range to be approximately 70 to 120 seconds.
Prolongation of the 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.
Shortening of the APTT usually reflects either elevation of factor VIII activity in vivo that most often occurs in association with acute or chronic illness or inflammation, or spurious results associated with either difficult venipuncture and specimen collection or suboptimal specimen processing.
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.
Mixing studies may be indicated to further evaluate specimens with an unexplained prolonged APTT.
1. 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
2. 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
3. Olson JD, Arkin CF, Brandt JT, et al: College of American Pathologists Conference XXXI on laboratory monitoring of anticoagulant therapy: laboratory monitoring of unfractionated heparin therapy. Arch Pathol Lab Med 1998;122:782-798