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  1. Anticoagulation is the key in the management of venous thromboembolism (VTE), atrial fibrillation (AF), mechanical heart valves, and idiopathic pulmonary arterial hypertension (IPAH).

  2. Critically ill patients are at increased risk for complications with anticoagulant therapy due to their underlying disease states, presence of thrombocytopenia, coagulopathy, renal and hepatic failure, need for invasive procedures, and the potential for major surgery.

  3. Intravenous unfractionated heparin (UFH) remains the most commonly utilized parenteral therapy when therapeutic doses are needed in the critically ill. Monitoring with the activated partial thromboplastin time (aPTT) or heparin level (anti–factor Xa assay) is required.

  4. Heparin resistance may occur due to nonspecific binding of the drug to various plasma proteins, altered intravascular volume, and/or increased heparin clearance. In cases of heparin resistance, anti-Xa level should be utilized for monitoring.

  5. Low-molecular-weight heparins (LMWHs) have several advantages over UFH including greater bioavailability and more predictable effects, lesser incidence of thrombocytopenia, and in general do not require monitoring except in patients who are morbidly obese, pregnant, or with severe renal insufficiency.

  6. Argatroban is a synthetic direct thrombin inhibitor that is approved for prevention and treatment of VTE in patients with heparin-induced thrombocytopenia (HIT).

  7. Novel oral anticoagulants inhibit either thrombin (factor IIa) or factor Xa. They include rivaroxaban, apixaban, edoxaban and dabigatran etexilate. These agents do not require routine monitoring.

  8. The risk/benefit of anticoagulant discontinuation for emergent procedures including surgery depends on the reason the patient is anticoagulated, the bleeding risk imparted by the procedure, and concomitant comorbidities.

  9. Warfarin and other vitamin K antagonists (VKAs) may be reversed with vitamin K and/or fresh frozen plasma (FFP).

  10. Four-factor prothrombin complex concentrate (PCC) is approved for use in the United States for warfarin reversal in the setting of severe bleeding.


Anticoagulation is the mainstay of therapy for VTE and is a key therapeutic component for a number of other clinical settings including atrial fibrillation (AF), mechanical heart valves, and idiopathic pulmonary arterial hypertension (IPAH). In the critical care setting, the use of anticoagulation is frequently warranted, but is often associated with an increased risk for complications based on underlying disease states, necessary invasive procedures, trauma, thrombocytopenia, coagulopathy, renal failure and hepatic failure, and the potential for major surgery. Reversing anticoagulation must be considered in certain clinical scenarios. The focus of this chapter will be anticoagulation in the intensive care unit (ICU), with a particular focus on therapeutic anticoagulation.

Anticoagulation in the critically ill patient requires therapeutic levels when treating an acute condition such as acute VTE. Given the high risk of morbidity and mortality caused by VTE, patients in the ICU, almost without exception, require VTE prophylaxis. Mechanical prophylaxis is used when pharmacologic prophylaxis is contraindicated or in certain lower-risk settings.

The ideal anticoagulant would be effective, easily administered with a predictable anticoagulant effect (oral, if the patient is capable) and rapid in onset, require no monitoring, and be ...

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