Activated Clotting Time

 

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.

Related Information

Activated Partial Thromboplastin Time
Heparin Antifactor Xa Assay
Heparin Neutralization

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 angioplasty.2,3

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

Footnotes

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.

References

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.