Activated Clotting Time (ACT) is a test which measures the time for whole blood to clot after the addition of particulate activators. Like the activated partial thromboplastin time, Activated Clotting Time measures the ability of the intrinsic pathway (reaction 1) to begin clot formation by activating factor XII. By checking the blood clotting status with ACT, the response to heparin therapy can be easily and rapidly monitored. Equally important is the use of the ACT in determining the appropriate dose of protamine sulfate required to reverse the effect of heparin on completion of surgical procedures and hemodialysis.
Both the aPTT and the ACT can be used to monitor heparin therapy. However, the ACT has several advantages over the aPTT. First, the ACT is more accurate than the aPTT when high doses of heparin are used for anticoagulation. This makes it especially useful during clinical situations requiring high-dose heparin, such as during CPB when high-dose anticoagulation is necessary at levels 10 times those used for venous thrombosis. The aPTT is not measurable at these high doses. The accepted goal for the ACT is 400-480 seconds during CPB.
Second, the ACT is not only less expensive, but it is also more easily and rapidly performed than the aPTT, which is time consuming and requires full laboratory facilities. The ACT can be performed at the bedside. This provides immediate information on which further therapeutic anticoagulation decisions can be based. The capability to perform the ACT at the “point of care” makes the ACT particularly useful for patients requiring angioplasty, hemodialysis, and CPB.
A nomogram adjusted to the patient’s baseline ACT is often used as a guide to reach the desired level of anticoagulation during these procedures. This same nomogram is used in determining the dose of protamine to be administered to neutralize the heparin when a return to normal coagulation is desired on completion of these procedures. The ACT is used in determining when it is safe to remove the vascular access after these procedures. The modified ACT test requires a smaller-volume blood specimen, automated blood sampling, standardized blood/reagent mixing, and faster clotting time results than the conventional ACT. The modified ACT is now being used more frequently.
Causes of Activated Clotting Time False Indications
- The ACT is affected by several biologic variables, including hypothermia, hemodilution, and platelet number and function.
- Factors affecting the pharmacokinetics of heparin (e.g., kidney or liver disease, heparin resistance) can affect ACT measurements.
- A partially or completely occluded specimen can increase ACT measurements.
- Drugs such as Aprotinin (a Serine Protease Inhibitor used during CPB) can prolong the ACT when Celita is used as the activator.
Normal Activated Clotting Time
In healthy patient the normal Activated Clotting Time ranges between 70 to 120 seconds. When Activated Clotting Time is used to monitor therapeutic procedures, the therapeutic range for anticoagulation increases to 150-210 seconds. Normal ranges and anticoagulation ranges vary according to particular therapy.
Causes of High Activated Clotting Time
- Heparin Administration: Heparin, along with antithrombin III, interrupts in the action of several coagulation proteins (except factor VII). As a result, the intrinsic pathway of coagulation is inhibited. This pathway is measured by the ACT and is therefore prolonged.
- Clotting Factor Deficiencies: Deficiencies in any clotting factor associated with the intrinsic pathway will be associated with prolonged ACT.
- Cirrhosis of the Liver: Coagulation factors are proteins that are synthesized in the liver. Liver pathology therefore is associated with a reduction in coagulation factors; this prolongs the time required for the reactions of the intrinsic pathway and prolongs the ACT.
- Coumadin Administration: Deficiencies in the vitamin K clotting factors associated with the intrinsic pathway will cause a prolonged ACT.
- Lupus inhibitor: Lupus inhibitors are autoantibodies against components involved in the activation of the coagulation cascade and thus prolong the ACT.
Causes of Low Activated Clotting Time
Thrombosis: In thrombotic syndromes in which secondary hemostasis is inappropriately stimulated, the ACT may be shortened.