Antifactor Xa activity in intensive care patients receiving thromboembolic prophylaxis with standard doses of enoxaparin

Standard subcutaneous dosing of unfractionated heparin for venous thromboembolism prophylaxis in surgical ICU patients leads to subtherapeutic factor Xa inhibition

“…A variety of ICU conditions, including sepsis, multiple organ dysfunction, high body weight, peripheral edema, and vasopressor requirement, have all been identified as risk factors for subtherapeutic anticoagulation with subcutaneously administered drugs [9,[17][18][19]. By corollary, peripheral vasoconstriction from hypovolemia, hypotension, hypothermia, or sepsis may contribute to decreased absorption of subcutaneous drugs such as unfractionated heparin.…”

“…While failure of prophylaxis may be due to a variety of different mechanisms, several studies in ICU patients suggest that subtherapeutic dosing of prophylaxis may be contributory. An observational study found that a high proportion of ICU patients had subtherapeutic anti-factor Xa (aFXa) levels after receiving standard prophylactic doses of the LMWH enoxaparin [9,10]. However, it is unknown if standard prophylactic dosing of subcutaneously administered unfractionated heparin, a common alternative to LMWH, is similarly subtherapeutic in ICU populations.…”

The Provision of Thromboprophylaxis and the Prediction of Renal Recovery in Critically Ill Patients with Acute Kidney Injury

“…Conventional target peak anti-Xa levels for thromboprophylaxis in a general ward population are 0.1-0.40 IU/ml [18,19]. The difference in peak anti-Xa between enoxaparin groups was not found to be significant, and this is again most likely due to small sample size, as our previous RCTs with approximately 80 patients each, were both able to demonstrate a significant difference in anti-Xa levels with varying doses of enoxaparin.…”

Primum non nocere – NICE guidelines on venous thromboembolism

“…The NICE guideline recommends the use of VTE prophylaxis according to the reason for admission, rather than specifically addressing the particular spectrum of medications and conditions encountered in critical care. Whilst there is concern regarding the risk of accumulation of anticoagulant and bleeding due to renal impairment, critically ill patients receiving vasopressors may have suboptimal absorption of subcutaneous medications and actually require larger amounts of LMWH to achieve adequate thromboprophylaxis [25]. Equally, despite abnormal coagulation screens, many critical care patients have increased thrombin generation [26] and are more likely to develop thrombosis than to bleed.…”