Intracardiac thrombosis can complicate a variety of conditions and lead to devastating consequences as a result of peripheral embolization. Long-term therapeutic oral anticoagulation (OAC) is effective for the prevention of thromboembolism in these conditions but carries attendant risks including major bleeding. Understanding the risks and benefits of long-term oral anticoagulant therapy for various cardiac conditions is essential for ensuring the best clinical outcomes.
These agents affect the coagulation protein cascade to reduce thrombosis.
1. Unfractionated heparin
Unfractionated heparin (UFH) binds to antithrombin (AT), markedly increasing the effect of AT in neutralizing thrombin and activating factor X (factor Xa). The effectiveness of UFH varies greatly from person to person due to its interactions with several plasma proteins and the endothelium, making monitoring the effects of full-dose UFH on hemostasis imperative. Monitoring of anti-factor Xa (anti-Xa) levels is recommended for accurate determination of the anticoagulant effects of UFH, and is considered more reliable compared to the previous use of activated partial thromboplastin time (aPTT). In certain dynamic situations where a higher level of anticoagulation is needed (e.g., during coronary interventions), the activated clotting time (ACT) is used to monitor its effect, and the dose of UFH is adjusted to keep the ACT at 250–300 seconds or greater. When given intravenously, the effects of UFH are immediate. It is usually administered as a bolus, followed by a continuous intravenous infusion, but may also be administered in divided therapeutic doses subcutaneously. The effects of UFH usually dissipate within 6 hours and its effects can be reversed almost completely with the use of protamine, which makes its use attractive in situations where bleeding risk is perceived to be high.
2. Low-molecular-weight heparin
Low-molecular-weight heparins (LMWHs) are breakdown products of UFH and have a selective effect on factor Xa. They bind more selectively to plasma proteins compared to UFH, so the dosing is more predictable. They are associated with lower bleeding risk, and laboratory monitoring is usually not necessary when dosage is based on body weight. Factor Xa levels, but not aPTT or ACT, can be used to monitor their effects. LMWHs are usually administered subcutaneously twice daily, and their effects are not easily reversed by protamine. They are contraindicated in the context of advanced chronic kidney disease (CKD). Since the dosing is weight based, the effects are less reliable among those with a very high body mass index.
3. Intravenous direct thrombin inhibitors
Bivalirudin and argatroban inhibit thrombin formation and are useful when UFH and LMWH are contraindicated in conditions such as heparin-induced thrombocytopenia (HIT). These agents are administered by bolus followed by a continuous infusion and inactivate both free and fibrin-bound thrombin. They do not bind to plasma proteins and, therefore, have a more predictable pharmacologic response, but their therapeutic ...