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Chapter 239: Thrombotics and Antithrombotics

David E. Slattery; Charles V. Pollack, Jr

INTRODUCTION

Antithrombotic therapy (i.e., anticoagulants, antiplatelet agents, and fibrinolytics) is used to treat or reduce the risk of arterial and venous thromboembolic conditions, including acute coronary syndrome, deep venous thrombosis and pulmonary embolism (collectively, venous thromboembolic disease), transient ischemic attack, and ischemic stroke (Table 239-1). Moreover, antithrombotic agents help prevent occlusive vascular events in patients at risk for thrombosis due to atherosclerotic arterial disease, atrial fibrillation, medical illness with immobility, or surgical insult. These agents, however, can cause life-threatening complications, primarily serious or life-threatening hemorrhage. Detailed management strategies for thromboembolic disorders are discussed in their respective chapters (see Chapter 49, “Acute Coronary Syndromes”; Chapter 56, “Venous Thromboembolism Including Pulmonary Embolism”; and Chapter 167, “Stroke Syndromes”).

TABLE 239-1Indications for Antithrombotic Therapy
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TABLE 239-1 Indications for Antithrombotic Therapy
Clinical Indication Comments
Treatment of Deep Venous Thrombosis and Pulmonary Embolism
Unfractionated heparin 80 units/kg IV bolus followed by 18 units/kg per h continuous IV infusion, with the aPTT checked after 6 h and the infusion adjusted to maintain anti-FXa activity 0.3–0.7 IU/mL or aPTT 1.5–2.5 times reference range (e.g., 68–106 s) with concurrent institution of warfarin

In most cases, heparin and warfarin started simultaneously, with an overlap of 3–5 d.

Warfarin is monitored and dose adjusted to a target INR of 2.0–3.0 in most patients.
Enoxaparin 1 milligram/kg SC every 12 h or 1.5 milligrams/kg SC once a day

Laboratory monitoring not routinely required (see text)

If CrCl <30 mL/min: 1 milligram/kg SC daily
Dalteparin 200 units/kg SC once daily or 100 units/kg SC twice daily Not FDA approved for this indication

Fondaparinux weight-tiered regimen

 <50 kg: 5 milligrams SC once a day

 50–100 kg: 7.5 milligrams SC once a day

 >100 kg: 10 milligrams SC once a day

Laboratory monitoring not routinely required

Avoid in patients with CrCl <30 mL/min
Dabigatran 150 milligrams PO twice daily

Following 5–10 d of initial therapy with parenteral anticoagulant

Avoid in patients with CrCl <30 mL/min or on hemodialysis
Rivaroxaban 15 milligrams PO twice daily for 21 d with food, followed by 20 milligrams PO once daily with food Avoid use in patients with CrCl <30 mL/min
Apixaban 10 milligrams PO twice daily for 7 d, followed by 5 milligrams twice daily

Reduce dose by 50% if patient taking dual strong VYP3A4 and P-glycoprotein inhibitors.

If Cr >1.5 milligrams/dL and either ≥80 years of age or body weight ≤60 kg: 2.5 milligrams twice daily
Edoxaban 30 milligrams PO daily (if ≤60 kg) or 60 milligrams PO daily (if >60 mg)

Following 5–10 d of initial therapy with parenteral anticoagulant

If CrCl 15 to 50 mL/min: 30 milligrams PO daily

If CrCl <15 mL/min: use not recommended

Streptokinase 250,000 units IV bolus, followed by 100,000 units/h continuous IV infusion for 1–3 d

or

Alteplase 100 milligrams IV infused over 2 h

or

Tenecteplase weight-tiered single IV bolus

 <60 kg: 30 ...

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