This chapter will review the pharmacotherapy for prevention and treatment of venous thromboembolism according to the American College of Chest Physicians evidence-based clinical practice guidelines on antithrombotic therapy and prevention of thrombosis.
Introduction
The threat of pulmonary embolism (PE) is a daily concern for patients in the intensive care unit (ICU), who typically have one or more risk factors for venous thromboembolism (VTE), the precursor of pulmonary embolism.
Risk factors for VTE
See Table 24.1 .
Surgery | Major surgery, especially cancer-related surgery, hip and knee surgery |
Trauma | Multisystem trauma, especially spinal cord injury and fractures of the spine |
Malignancy | Any malignancy, active or occult chemotherapy and radiotherapy |
Acute medical illness | Stroke, right-sided heart failure, sepsis, inflammatory bowel disease, nephrotic syndrome, myeloproliferative disorders |
Drugs | Erythropoiesis-stimulating drugs, estrogen-containing compounds |
Patient-specific factors | Prior thromboembolism, obesity, increasing age, pregnancy |
ICU-related factors | Prolonged mechanical ventilation, neuromuscular paralysis, severe sepsis, vasopressors, platelet transfusions, immobility |
Prevalence of VTE
See Fig. 24.1 .
Thromboprophylaxis
- •
Thromboprophylaxis for specific conditions ( Table 24.2 )
Table 24.2
CONDITIONS
REGIMENS (ANY DRUG OR MECHANICAL DEVICE)
UFH
LMWH
FONDAPARINUX
ASA
APIXABAN
DABIGATRAN
RIVAROXABAN
WARFARIN
IPC
Acute medical illness
+
+
+
General and abdominal-pelvic surgery
Low risk
Moderate risk
High risk
+
+
+
+
+ a
+ a
+
+
+ b
Abdominal-pelvic surgery for cancer
+
Thoracic Surgery
Moderate risk
High risk
+
+
+
+
+
+ b
Cardiac surgery with complications
+
+
+ b
Craniotomy
+
Spinal surgery
+
+
+
Hip or knee surgery
+ c
+
+ c
+ c
+ c
+ c
+ c
+ c
+ c
Major orthopedic surgery
+
+
+ d
+ d
+ e
Major trauma
+
+
+
Head or spinal cord injury
+
+
+ b
Any of the above + active bleeding or high risk of bleeding
+
a If contraindicated to UFH or LMWH
c Alternative ( LMWH , Preferred)
- •
Pharmacotherapy according to specific conditions ( Table 24.3 )
Table 24.3
ANTICOAGULANT
USUAL DOSE
DOSE ADJUSTMENT
COMMENTS
Unfractionated Heparin
UFH
5000 units SubQ q8–12h
BMI ≥50: 7000 units q8h
LWMH has a lower risk of HIT compared to UFH
LMWH is equivalent to UFH for most conditions in ICU except for orthopedic procedures involving the hip and knee (LMWH is superior to UFH)
First dose of LMWH should not be given <12 h after surgery
Low-Molecular-Weight Heparins
Enoxaparin
40 mg SubQ q24h
or
30 mg SubQ q12h
BMI >40: 0.5 mg/kg q24h
CrCl <30: 30 mg q24h
Dalteparin
2500–5000 units SubQ q24h
No adjustment
Factor Xa Inhibitors
Fondaparinux
2.5 mg SubQ q24h
CI: <50 kg or CrCl <30: avoid
Useful for patients with history of HIT
Betrixaban (Bevyxxa)
160 mg ×1 then 80 mg PO daily with food ×35–42 days
CrCl 15–29 or strong P-gp inhibitors (e.g., amiodarone, azithromycin, clarithromycin, ketoconazole, verapamil): 80 mg ×1 then 40 mg PO daily with food ×35–42 days
CrCl <15 or dialysis: not studied
New prophylactic anticoagulant for acute medical illness
Antiplatelet
Aspirin
160 mg PO daily
Caution in CrCl <10
N/A
Direct Oral Anticoagulants
Apixaban
2.5 mg PO BID
CrCl <30: excluded from studies
Apixaban, dabigatran, and rivaroxaban can elevate the INR
Dabigatran
150 mg–220 mg PO daily
CrCl ≤30: excluded from studies
Rivaroxaban
10 mg PO daily
CrCl <30: avoid
Vitamin K Antagonist
Warfarin
5–10 mg PO daily for 2 days, then titrate to INR 2–3
Monitor INR closely
Monitor INR closely
a Refer to specific conditions in Table 24.2
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