Chapter 4

Intracardiac thrombi can form and lead to devastating consequences as a result of obstruction of blood flow and/or peripheral embolization. Long-term anticoagulation is recommended for primary and secondary prevention of thromboembolism in many cardiac conditions, and in selected conditions, it is essential. There are, however, risks associated with the use of anticoagulants, and an understanding of the risks and benefits of anticoagulant therapy for various cardiac conditions is important.

### Anticoagulants

These agents affect the coagulation protein cascade to reduce thrombosis.

#### Unfractionated Heparin

Unfractionated heparin (UFH) binds to antithrombin III, markedly increasing the effect of antithrombin III in neutralizing thrombin. It also inhibits the activation of factors IX and X. The effectiveness of UFH varies greatly from person to person due to its interactions with a number of plasma proteins and the endothelium. Monitoring the effects of full-dose UFH on hemostasis is mandatory. The activated partial thromboplastin time (aPTT) is used to monitor the effects of UFH and is titrated to 1.5–2.0 times greater than control. In certain situations, a higher level of anticoagulation is needed; for example, during coronary interventions where the activated clotting time (ACT) is used to monitor its effect and the dose of UFH is adjusted to keep the ACT 250–300 seconds or greater. When given intravenously, the effects of UFH are immediate. It is usually given as a bolus, followed by a continuous intravenous infusion. It may also be given in therapeutic doses subcutaneously. The effects of UFH will dissipate within 6 hours. Protamine can be given to reverse its effects more quickly. UFH can also be given subcutaneously in smaller doses, which will not affect the aPTT, for primary prevention of deep venous thrombosis.

#### Low-Molecular-Weight Heparin

Low-molecular-weight heparins (LMWHs) are breakdown products of UFH. They have a greater effect on factor X than on thrombin. LMWHs bind less to plasma proteins than UFH, and therefore, the dosing is more predictable. They are more resistant to neutralization by platelet factor 4 than UFH and have less inhibitory effect on platelet function than UFH. LMWHs have a more predictable effect on coagulation than UFH, and laboratory monitoring is usually not necessary, but activated factor Xa levels can be used to monitor their effects. LMWHs are usually administered subcutaneously twice daily. They are not easily reversed by protamine. LMWH can also be given in smaller doses for the primary prevention of deep venous thrombosis.

#### Intravenous Thrombin Inhibitors

Lepirudin, bivalirudin, and argatroban inhibit thrombin formation and are useful when UFH and LMWH are contraindicated. These agents are administered by bolus followed by a continuous infusion. These agents 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 window is narrow. The aPTT is used to monitor their effect. The international normalized ratio (INR) is ...

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