Activated Partial Thromboplastin Time

Test Utility

PT and PTT are complementary tests used in the assessment of factors involved in the clotting cascade in vivo. They are often used together in routine presurgical evaluation. While sensitivities of various PTT formulations to specific factors vary, under most circumstances the PTT will fall outside the normal range if single intrinsic or common factor activities fall below 30%–40% or if milder deficiencies, involving multiple factors, are present. Fibrinogen concentrations significantly below 100 mg/dL also prolong the PTT.

In addition to deficiencies, specific inhibitors of the factors involved in PTT-initiated clotting cascade can also cause an abnormally prolonged test result. Most PTT test formulations show sensitivity to lupus anticoagulants (LA), which allows the use of the test in the initial screening for LA.

Besides screening for factor inhibitors of deficiencies, PTT has found numerous other uses. While not ideal for these purposes, PTT is also currently utilized to monitor treatment with unfractionated heparin and some direct thrombin inhibitors in most laboratories in the United States because of its wide availability and low cost (see Chapter 159 ). PTT is a suboptimal test for assessing therapy with newer oral direct thrombin inhibitor dabigatran due to a shallow response curve (see Chapter 159 ). Use of PTT in the detection of LA is covered elsewhere (see Chapter 158 ).

Test Limitations

Although PTT is sometimes ordered in trauma, disseminated intravascular coagulation, and liver disease, it has several disadvantages for screening for multifactor deficiencies compared with PT. First, high FVIII concentration in inflammation and liver disease can mask factor deficiencies by shortening the PTT. Second, PTT measures some factors that are not associated with bleeding risk. Deficiencies in FXII, kallikrein, and HMWK are not associated with increased risk of hemorrhage as they do not seem to play a significant role in clotting cascade activation in vivo . Third, LA and heparin contamination from line draws can lead to falsely high results more frequently than in PT determination. Fourth, in the setting of trauma, the additional incubation required for contact activation makes PTT a slower test to perform than PT. Although PTT will be increased in vitamin K deficiency and warfarin use, it is not used for monitoring therapy.

Interlaboratory Variation

Large variations exist in commercial reagent preparations, instrument detection protocols, and sensitivities to clotting inhibitors. For these reasons, each laboratory establishes its own reference range specific to their reagent/instrument combination and assesses sensitivity to relevant anticoagulants and factor deficiencies. This means that PTT values in seconds are not comparable between different systems. Moreover, PTT reagents vary in their sensitivity to LA. Some reagents are formulated with increased phospholipid content or lupus anticoagulant insensitive activators to neutralize most LA, whereas others are specifically designed to be more sensitive. In case of LA, these modifications frequently result in PTT being normal in one laboratory and substantially prolonged in another.