Activated Clotting Time (ACT)

The activated whole blood clotting time is a rapid bedside test for monitoring anticoagulation with unfractionated heparin. Changes in the ACT are directly and linearly proportional to the concentration of heparin. The degree of prolongation of the ACT is a useful index of a patient's level of anticoagulation. Heparin dose may be adjusted according to the result. 

The APTT is the preferred test for monitoring standard heparin therapy (e.g. treatment of venous thromboembolism), because it is more precise and less subject to technical variability.  However, the APTT is unsuitable for measuring high concentrations of heparin because it is frequently prolonged beyond the measurable range.  

ACT is the recommended test for monitoring the high doses of heparin used during cardio-pulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), percutaneous transluminal coronary angioplasty, interventional neurology, and hemodialysis. 

The ACT is a test of whole blood that uses a strong contact activator of the intrinsic coagulation pathway, either celite, kaolin, or glass balls. The test is dependent on the presence of endogenous platelets as the source of phospholipid. An automated instrument electronically detects clot formation. The time to clot formation is the activated clotting time. 

The ACT is designed to be prolonged about 100 seconds above baseline for each unit per milliliter of heparin concentration in a typical patient. For example, heparin concentrations between 1 and 3 units/mL give ACT results ranging between 130 and 350 seconds. 

The usual monitoring protocol consists of a baseline ACT followed by a bolus of heparin.  The baseline ACT should be within the reference range. During CPB, heparin is titrated to maintain an ACT between 400 and 600 seconds. This corresponds to a heparin level of 4 to 5 units/mL. During ECMO, heparin is titrated to maintain the ACT between 220 and 260 seconds. 

During bypass, the ACT is repeated every 15 to 20 minutes; if the result is less than 450 seconds, additional heparin is administered. At the completion of CPB, heparin is neutralized with protamine and the ACT is performed again to ensure that it has returned to baseline levels. 

Many factors besides heparin may affect the ACT. These include hemodilution, hypothermia, cardioplegic solutions, platelet dysfunction, hypofibrinogenemia, other coagulopathies and certain drugs. ACT is prolonged in patients with antiphospholipid antibodies and may not demonstrate a linear response to heparin. If unexpected test results are obtained, more specific coagulation tests should be performed for further investigation.

The ACT reference range varies considerably depending on the activator and instrument. It usually falls between 70 and 180 seconds.

Specimen requirement is 2 mL of whole blood collected in a special tube containing activator. It should be immediately mixed and inserted into the instrument.

References

Hattersley PG. Activated coagulation time of whole blood. JAMA. 1966 2;196(5):436-40.

Hattersley PG. Activated coagulation time as screening test. JAMA. 1972 30;222(5):583-4.

Paniccia R, Fedi S, Carbonetto F, Noferi D, Conti P, Bandinelli B, et al. Evaluation of a new point-of-care celite-activated clotting time analyzer in different clinical settings. The i-STAT celite-activated clotting time test. Anesthesiology. 2003; 99(1):54-9.

Horton S and Augustin S. Activated Clotting Time (ACT), Methods Mol Biol, 2013;992:155-67.