From: Elizabeth M. Van Cott, M.D., and Michael Laposata, M.D., Ph.D., "Coagulation." In: Jacobs DS et al, ed. The Laboratory Test Handbook, 5th Edition. Lexi-Comp, Cleveland, 2001; 327-358.
Index of Tests
Activated Clotting Time [CO000100]
Synonyms ACT; Activated Coagulation Time
Applies to Heparin
Abstract The ACT is a bedside clotting test that is most
useful for monitoring high-dose heparin anticoagulation.
Specimen Whole blood
Container One tube containing an activator of coagulation,
such as celite (diatomaceous earth), kaolin, or glass particles.
For methods that use cartridges rather than tubes, whole blood may
be collected into a plastic syringe or tube and then immediately
transferred into the cartridge.
Collection Routine venipuncture. Do not collect from a line
that contains heparin. Some tubes require approximately 10 vigorous
shakes to disperse the activator; other tubes require gentle mixing.
Perform test immediately.
Storage Instructions Specimen cannot be stored; test is performed
immediately after collection.
Turnaround Time Minutes
Reference Interval Reference range varies considerably depending
on the method; it usually falls somewhere within 70-180 seconds.
With cardiopulmonary bypass heparinization, the goal is to exceed
400-500 seconds (commonly >480 seconds), depending on the method,
representing a mean heparin level of approximately 4-5 units/mL.1,2 For other indications, the ACT goal is typically lower than it is
for cardiopulmonary bypass. The ACT goal can also vary depending
on the test method. For example, Hemochron® ACT measurements
tend to be higher than HemoTec® ACT measurements, although this
is not always the case. A HemoTec® ACT >275-300 seconds or
a Hemochron® ACT >350 seconds has been recommended for coronary
Use Monitor high-dose heparin anticoagulation, such as during
cardiopulmonary bypass surgery. May also be used when an immediate
measure of heparin anticoagulation is required at the bedside, such
as with extracorporeal membrane oxygenation (ECMO), hemodialysis,
cardiac catheterization, and vascular surgery.
Limitations The ACT is less precise than the PTT, and lacks
high correlation with the PTT or with heparin antifactor Xa levels.
The ACT is influenced by a number of variables, including platelet
count, platelet function, lupus anticoagulants, factor deficiencies,
ambient temperature, hypothermia, and hemodilution. The various
methods are not standardized, and therefore, results from different
methods are not interchangeable. Aprotinin prolongs celite-based
ACTs but generally not kaolin-based ACTs. Thus, celite-based ACTs
may overestimate the amount of heparin anticoagulation when aprotinin
is present. However, very high doses of aprotinin, such as following
a large initial bolus, may prolong kaolin-based ACTs.
Methodology Whole blood is collected into a tube containing
an activator of coagulation, such as celite (diatomaceous earth),
kaolin, or glass particles.4 These activate the intrinsic
pathway of coagulation, causing the blood to clot. The tubes are
placed into a specialized coagulation analyzer (eg, Hemochron®,
International Technidyne; Actalyke®, Helena Laboratories), which
measures the time it takes for the blood to clot. Clot formation
can be detected by the mobility of a magnet inside the blood test
tube. As the instrument rolls the test tube, the magnet rolls along
the bottom. When the clot forms, the clot pulls the magnet away
from a magnetic detector. With other methods, whole blood is placed
into a specialized cartridge that contains an activator of coagulation,
such as celite, kaolin or silica, and the clotting time is measured
(eg, HemoTec®, Medtronics Inc; i-STAT, i-STAT Corp; GEM PCL,
Instrumentation Laboratories). The Medtronics instrument detects
clotting by a plunger that moves through the blood sample. When
a clot forms, the clot resists the plunger. With the i-STAT instrument,
clotting is detected indirectly by the presence of a substrate for
thrombin in the cartridge. The substrate resembles the site on fibrinogen
that thrombin normally cleaves to form fibrin clot. Thrombin is
generated as coagulation is activated, and it cleaves the substrate,
releasing an electroactive compound that is detected amperometrically.
With GEM PCL cartridges, clot formation is monitored as the instrument
draws the blood back and forth across a light detection window.
Once the blood clots, the blood no longer flows across the window.
Additional Information With high doses of heparin, the PTT
cannot be used to monitor heparin therapy because the PTT is unclottable.
The ACT or heparin antifactor Xa levels are used instead of the
PTT in such situations. Rarely, ACTs are collected in anticoagulated
tubes and the test is performed in a central laboratory.1
1. 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(9):782-98.
2. Hirsh J, Warkentin TE, Raschke R, et al, "Heparin and Low-Molecular
Weight Heparin. Mechanisms of Action, Pharmacokinetics, Dosing Considerations,
Monitoring, Efficacy, and Safety,"Chest, 1998, 114(5 Suppl):489-510.
3. Ferguson JJ, "Conventional Antithrombotic Approaches,"Am
Heart J, 1995, 130(3 Pt 2):651-7.
4. Hattersley PG, "Activated Coagulation Time of Whole Blood,"J
Am Med Assoc, 1966, 196(5):436-40.
Despotis GJ, Joist JH, Hogue CW, et al, "More Effective Suppression
of Hemostatic System Activation in Patients Undergoing Cardiac Surgery
by Heparin Dosing Based on Heparin Blood Concentrations Rather Than
ACT,"Thromb Haemost, 1996, 76(6):902-8.