About anticoagulant drug testing, activated clotting time (ACT)

Activated clotting time (ACT) is a test primarily used to monitor high-dose unfractionated (standard) heparin therapy. Heparin is a drug that inhibits blood clotting (anticoagulation) and is usually given by injection into a vein (intravenous, IV) or as a continuous infusion. High doses of heparin may be used during medical or surgical procedures where blood clotting needs to be prevented (such as heart bypass surgery).

Moderate doses of heparin are used to prevent and treat inappropriate blood clot formation (thrombosis or thromboembolism) and are monitored by the partial thromboplastin time (PTT) or heparin anti-factor Xa test. Monitoring is an important part of anticoagulation therapy because the blood-thinning (anticoagulant) effects of heparin affect everyone slightly differently. If the amount of heparin used is not sufficient to inhibit the body's coagulation system, blood clots may form in blood vessels throughout the body. If too much heparin is used, it can cause excessive bleeding and even be life-threatening.

For example, high doses of heparin are administered before, during, and for a short time after open heart surgery. During these surgeries, the patient's heart and lungs are often bypassed. This means their blood is filtered and oxygenated outside the body through mechanical devices. Contact of blood with artificial surfaces activates platelets and coagulation functions, initiating a series of steps that lead to the formation of blood clots. High-dose heparin prevents blood clots from forming, but leaves the body in a delicate dynamic balance between clotting and bleeding. At this level of anticoagulation, PTT is no longer a clinically useful monitoring tool. The PTT test involves an in vitro coagulation reaction, which does not clot when heparin levels are high. In this case, ACT must be used for monitoring.

Activated clotting time (ACT) is commonly used to monitor coagulation before, during, and shortly after high-dose heparin therapy that requires preventing blood clotting, such as bypass surgery, coronary angioplasty, and dialysis.

ACT is a rapid test that can be administered at the patient's bedside before surgery or other medical procedures. It can also be done in or near the operating room, during or immediately after surgery. (The ACT test measures relatively rapid changes in heparin infusion, helping to achieve and maintain a constant level of anticoagulation throughout a surgical or medical procedure. Once the procedure is completed and the patient's condition is stable, the heparin dose is typically reduced.

ACT measures the inhibitory effect of heparin on the body's coagulation system, not the actual level of heparin in the blood. The sensitivity of the ACT test to heparin depends on the method used. Some ACT tests are designed to monitor lower levels of heparin, while others are best suited for monitoring higher levels of heparin. When heparin reaches therapeutic maintenance levels, ACT is often replaced by PTT as a monitoring tool.

The ACT test is also sometimes used to monitor regular-dose heparin therapy with documented lupus anticoagulant (LAC). PTT testing cannot be used in these patients because LAC interferes with PTT. In rare clinical situations, the ACT test can also be used to monitor the inhibitory effect of another class of anticoagulant drugs (direct thrombin inhibitors, such as argatroban) on the coagulation system.

ACT is given after an initial dose of (suppository) heparin and before the start of open heart surgery or other procedures requiring high levels of anticoagulation. During surgery, ACT was measured at intervals to achieve and maintain stable heparin anticoagulation levels. After surgery, ACT is monitored until the patient's condition is stabilized and the heparin dose is reduced and/or neutralized by an anticoagulant such as triamine sulfate.

ACT is also sometimes measured during a bleeding episode or as part of the bedside assessment of heparin anticoagulation levels, particularly if the patient has lupus anticoagulant (LAC).

The test may also be used when a person is receiving direct thrombin inhibitor therapy (such as argatroban)

ACT is measured in seconds: the longer the clotting time, the greater the degree of clotting inhibition (anticoagulation). During surgery, ACT is kept above a low time limit within which blood clots will not form in most people. There is currently no broad consensus as to what this lower limit should be. This varies from hospital to hospital and depends in part on the method used to determine ACT.

It is important to assess the patient's response to the lower ACT limit and heparin dosage. The amount of heparin required to achieve and maintain a certain ACT (eg, 300 seconds) will vary depending on the body's coagulation potential at that ACT. If clotting or bleeding problems exist, dose and ACT may need to be adjusted accordingly. After surgery, ACT can be maintained within a narrow range (e.g., 175-225 seconds) until the patient's condition is stable.