Risk for Post-operative Venous Thromboembolism in Patients Receiving Enoxaparin Prophylaxis
Low anti-Factor Xa indicative of inadequate enoxaparin dosing is associated with a higher incidence of post-surgical Venous Thromboembolism.
Key Takeaway
This study shows that among surgical patients receiving post-operative enoxaparin for venous thromboembolism (VTE) prevention, those having initial low vs in-range/high anti-Factor Xa (aFXa) were at significantly higher risk for 90-day post-operative VTE.
High aFXa levels were not associated with 90-day clinically relevant bleeding (CRB) or major bleeding (MB).
Why This Matters
Despite receiving chemical anticoagulation, surgical patients are at increased risk for “breakthrough” VTE.
Moreover, surgical patients exhibit variable pharmacodynamic responses to enoxaparin, which are demonstrated by differences in aFXa levels, a marker of the extent of anticoagulation.
Study Design
This is a pooled analysis of 8 clinical trials conducted at the University of Utah including 985 patients (mean age, 51.8 years) who underwent surgery and were receiving post-surgery prophylactic enoxaparin.
Peak aFXa level in response to initial enoxaparin dosage was recorded in all patients, who were then followed up for 90 days.
Following endpoints were evaluated:
90-day symptomatic VTE (symptomatic deep vein thrombosis [DVT], pulmonary embolus, portal vein thrombosis, inferior vena cava thrombosis and central venous catheter-associated DVT);
CRB (requiring treatment change, including enoxaparin discontinuation, unexpected transfusion, interventional/bedside procedure, return to operating room and unexpected visit to emergency room); and
MB (defined by the International Society of Thrombosis and Hemostasis).
Funding: Plastic Surgery Foundation; others.
Key Results
Included patients underwent reconstructive (n=507), thoracic (n=198), colorectal (n=116), orthopaedic (n=109) and trauma (n=55) surgeries.
Among patients (n=376) receiving once-daily (OD) enoxaparin, 62.5%, 35.1% and 2.4% had low (<0.3 IU/mL), in-range (0.3-0.5 IU/mL) and high (>0.5 IU/mL) initial aFXa levels, respectively.
Among patients (n=537) receiving twice-daily (BD) enoxaparin, 27%, 59% and 14% had low (<0.2 IU/mL), in-range (0.2-0.4 IU/mL) and high (>0.4 IU/mL) initial aFXa levels, respectively.
Overall, 23 (2.3%) patients had 90-day VTE, with no differences observed in those receiving BD vs OD enoxaparin (2.6% vs 2.0%; P=0.67).
Patients with initial low vs in-range/high aFXa levels had higher risk for VTE (4.2% vs 1.3%; logrank P=0.007).
Initial low aFXa predicted VTE risk in patients receiving BD (6.2% vs 1.5%; logrank P=0.003) and not OD enoxaparin (3.0% vs 0.7%; logrank P=0.14).
41 (4.2%) and 21 (2.1%) patients had CRB and MB, respectively.
Patients receiving BD vs OD enoxaparin were at higher risk for CRB (5.6% vs 2.2%; P=0.009) and MB (3.3% vs 0.5%; P=0.003).
However, high aFXa vs low/in-range aFXa was not associated with 90-day CRB (4.8% vs 2.9%; logrank P=0.34) and MB (3.6% vs 1.6%; P=0.18).
Limitations
Trials from only 1 institution were included.
Low aFXa as a direct cause of VTE could not be proved.
Day-to-day care may have been under-reflected.
Real-time effects of enoxaparin dose adjustments on VTE were not assessed.
Regression analysis was not performed.
Possibility of high aFXa levels in patients who bled before enoxaparin reached a steady state was not investigated.
Pannucci CJ, Fleming KI, Varghese TK, Stringham J, Huang LC, Pickron TB, Prazak AM, Bertolaccini C, Momeni A. Low anti-Factor Xa level predicts 90-day Symptomatic Venous Thromboembolism in Surgical Patients Receiving Enoxaparin Prophylaxis: A Pooled Analysis of Eight Clinical Trials. Ann Surg. 2020 Oct 19 [Epub ahead of print]. doi: 10.1097/SLA.0000000000004589. PMID: 33086312
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