Interpretation

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. 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 test is helpful for identifying or excluding the presence of heparin, the platelet neutralization procedure (using a modified APTT method) for identifying or excluding lupus anticoagulant, the prothrombin time and dilute Russell's viper venom time 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, Plasma).

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.