Clinical Information

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

The 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.