The Activated Clotting Time (ACT) is a rapid, point-of-care test that measures the time it takes for whole blood to clot. It is predominantly used in clinical settings that require intense and rapid anticoagulation monitoring, such as cardiac surgery with cardiopulmonary bypass (CPB), percutaneous coronary interventions (PCI), or during extracorporeal membrane oxygenation (ECMO). Because it is a whole blood test, the ACT is influenced by several factors beyond just the medication administered. Understanding which drugs affect the activated clotting time and their specific mechanisms is critical for patient safety and therapeutic efficacy.
Anticoagulants that Prolong Activated Clotting Time (ACT)
Unfractionated Heparin (UFH)
Unfractionated heparin is the most common drug monitored by ACT during high-dose anticoagulation required for procedures like cardiopulmonary bypass. Heparin enhances the activity of antithrombin III, which inactivates clotting factors like thrombin and Factor Xa, slowing the clotting cascade. High doses of UFH are needed to achieve the prolonged ACT values (>400 seconds) required for certain procedures. Protamine sulfate reverses heparin's effects and normalizes ACT.
Direct Thrombin Inhibitors (DTIs)
This class of drugs, including intravenous agents like argatroban and bivalirudin, directly inhibits thrombin without needing antithrombin III. They are monitored using ACT, with bivalirudin used in PCI and argatroban as an alternative for patients with heparin-induced thrombocytopenia (HIT). Oral DTIs like dabigatran can also affect ACT but are not typically monitored this way.
Oral Anticoagulants
Oral anticoagulants can influence ACT results, though it's not the primary monitoring method. Warfarin, a vitamin K antagonist, inhibits clotting factor synthesis and can prolong ACT at high doses. Direct oral anticoagulants (DOACs) like rivaroxaban and apixaban, which inhibit Factor Xa, also prolong ACT, but less so than UFH or DTIs. INR monitors warfarin, and DOACs don't require routine monitoring.
Antiplatelet Drugs Affecting Clotting Time
Glycoprotein IIb/IIIa (GPIIb/IIIa) Inhibitors
Intravenous drugs such as abciximab, eptifibatide, and tirofiban block platelet receptors, preventing aggregation. In procedures like PCI, these inhibitors, when used with heparin, can further prolong ACT.
Other Antiplatelets
Other antiplatelet agents, including aspirin and P2Y12 inhibitors like clopidogrel and ticagrelor, have a variable and less significant effect on ACT. They are not primarily monitored by ACT but increase bleeding risk when combined with other anticoagulants.
Medications with Specific Effects on ACT
Heparin Reversal Agents
Protamine sulfate is the antidote for heparin, binding to it and rapidly reversing its anticoagulant effects and prolonged ACT.
Antifibrinolytic Agents
Medications like tranexamic acid inhibit clot breakdown to control bleeding. While not directly targeting ACT factors, their pro-clotting action can counteract a prolonged ACT, especially in the context of bleeding.
Other Factors That Can Influence ACT Results
ACT results are influenced by several non-pharmacological factors:
- Hypothermia: Cold temperatures slow clotting enzyme activity, prolonging ACT.
- Hemodilution: Diluted blood from procedures like CPB or fluid administration reduces clotting factor concentration, prolonging ACT.
- Thrombocytopenia: A low platelet count, crucial for clotting, can prolong ACT.
- Existing Coagulopathies: Pre-existing clotting factor issues can affect baseline ACT.
- Device Variability: Different ACT devices can yield varying results, so target ranges may be device-specific.
How Different Drug Classes Affect Activated Clotting Time
| Drug Class | Examples | Mechanism | Effect on ACT | Clinical Context for Monitoring |
|---|---|---|---|---|
| Unfractionated Heparin | Heparin | Enhances antithrombin III, inactivating clotting factors (IIa, Xa) | Markedly Prolonged | Cardiac surgery, ECMO, PCI |
| Direct Thrombin Inhibitors | Argatroban, Bivalirudin | Directly inhibits thrombin | Moderately to Markedly Prolonged | HIT, PCI |
| Factor Xa Inhibitors | Rivaroxaban, Apixaban | Inhibits Factor Xa | Mild to Moderate Prolongation | May affect test results, not routinely monitored with ACT |
| Vitamin K Antagonists | Warfarin | Inhibits vitamin K-dependent factors | Mild to Moderate Prolongation | Not routinely monitored with ACT (INR used) |
| GPIIb/IIIa Inhibitors | Abciximab, Eptifibatide | Blocks platelet aggregation receptors | Significantly Prolonged | Used with heparin during PCI |
| Heparin Antagonists | Protamine Sulfate | Neutralizes heparin | Normalizes (reverses prolongation) | After heparin use in procedures |
Conclusion
ACT is a crucial tool in acute care, providing rapid feedback on anticoagulation levels. Unfractionated heparin and direct thrombin inhibitors are key drugs that prolong ACT during procedures like cardiac surgery. Antiplatelet agents, oral anticoagulants, and factors like hypothermia and hemodilution also influence results. Clinicians need to consider all potential factors affecting ACT for accurate interpretation, dosage adjustments, and patient safety during critical procedures.
