Supportive and Preventive Medicine

or major bleeding rates with twice-daily regimens compared with thrice-daily regimens in nonsurgical

hospitalized patients (Chest 2011;140:374-81). Most of these patients were not critically ill and had few

comorbidities. A more recent observational study using the Premier Healthcare Database compared

thrice-daily with twice-daily dosing in 30,800 critically ill patients. No significant differences occurred

in VTE rates (6.16 vs. 6.23, p=0.8) or bleeding (0.23 vs. 0.33, p=0.084) in the propensity-matched cohort.

Bioavailability of subcutaneously administered drugs is reduced in critically ill patients with the

concomitant use of vasoactive drugs or the presence of edema, thereby potentially reducing the effect.

A high proportion of critically ill patients have acute kidney injury, which may limit the use of LMWH.

Reduced doses of LMWH (Table 9), with or without anti–factor Xa (anti-Xa) monitoring, may be

considered depending on risk-benefit assessment; however, LDUH is often preferred in critically ill

patients with a CrCl less than 30 mL/min/1.73 m2, particularly in patients receiving peritoneal dialysis,

hemodialysis, or continuous veno-venous hemofiltration.

Bleeding

Bleeding rates in critically ill patients vary, depending on the type of pharmacologic prophylaxis.

Patients at high risk of bleeding are often excluded from studies.

Patients at high risk of bleeding with a moderate to high risk of VTE may be considered for

mechanical VTE prophylaxis; however, pharmacologic prophylaxis should be reassessed when the

bleeding risk is no longer present.

Limited evidence exists to guide dosing in the critically ill population with obesity. An inverse

relationship between body weight and anti-Xa concentration may exist in patients with obesity;

however, the risk of VTE and the optimal anti-Xa concentrations to achieve are unclear. Some

clinicians may choose heparin 7500 units subcutaneously every 8 hours over heparin 5000 units

subcutaneously every 8 hours in patients with BMI greater than 40 kg/m2; however, several studies,

2016;36:740-8; Hosp Pharm 2016;51:376-81). There is also controversy regarding the optimal

approach to VTE prophylaxis with enoxaparin in patients with a BMI greater than 40 kg/m2;

approaches to dosing and anti-Xa level vary significantly because of the varying populations studied.

Common strategies include either a fixed dose of 40 mg subcutaneously twice daily or 0.5 mg/kg twice daily.

For patients with a BMI greater than 50 mg/m2, in addition to weight-based dosing, some clinicians use

If using anti-Xa–guided therapy, peak concentrations are typically ordered at steady state; they

should be obtained 3 to 5 hours after administration of the third or fourth dose of enoxaparin

initiation or dose change. Goal anti-Xa for VTE prophylaxis is 0.2 to 0.4 units/mL (HCA Healthc J

Med. 2023;4(2):105-109).

Oral Anticoagulants for VTE Prophylaxis

The only study evaluating direct oral anticoagulants (DOACs) for VTE prophylaxis in critically ill

patients was a substudy of extended duration (35-42 days) of betrixaban versus shorter duration (10 ± 4

days) LMWH in critically ill medical patients. Of the 7513 patients in the full cohort, 703 critically ill

patients were included in the substudy. Extended-duration betrixaban reduced the rate of VTE at 35-42

days from 7.95% to 4.27% (p=0.042). Major bleeding in the two groups was 1.14% and 3.13% (p=0.07).

These findings should currently be treated as exploratory, given that the full study had predefined

Betrixaban was removed from the market in April 2020 because of a lack of commercial success.