Author: V. Dimov, M.D.
Reviewer: S. Randhawa, M.D.
A 62-yo Caucasian male (CM) with a complicated past medical history (PMH), including gastrointestinal (GI) bleeding from esophageal varices, colon cancer and chronic renal insufficiency (CRI), is hospitalized with a deep vein venous thrombosis (DVT). He is obese and had a hemicolectomy 3 weeks ago.
Lovenox (enoxaparin) is started, warfarin (Coumadin) use is contraindicated due to history of gastrointestinal (GI) bleeding.
He will need anticoagulation with Lovenox (enoxaparin) for 6 months.
Is there any way to know if Lovenox (enoxaparin) dose is therapeutic? What do we check?
- factor Xa
- anti-Xa level
You have to check anti-Xa level. This is NOT factor Xa level, which most likely will be normal with Lovenox (enoxaparin) therapy.
PTT is not useful in monitoring therapy with LMWH. PTT should be used to monitor treatment with UFH, i.e. regular IV heparin.
What is anti-Xa level? Is it some "special" factor anti-Xa?
No, there is no factor anti-Xa. There is a factor Xa, just like the other 12 factors in the anticoagulation cascade (there is no factor VI).
Anti-Xa level is determined by a simple mixing study. Patient plasma is added to a known amount of factor Xa with antithrombin. LMWH in the patient plasma will bind to antithrombin and inhibit factor Xa. The amount of residual factor Xa is inversely proportional to the amount of LMWH the plasma.
Low anti-Xa value indicates a high level of anticoagulation. High anti-Xa level indicates a low level of anticoagulation. For example, anti-Xa level of 0.5 indicates adequate anticoagulation, a level of 3 is not sufficient.
Fig 1. The coagulation cascade. Legend: Black arrow = conversion/activation of factor. Red arrows = action of inhibitors. Blue arrows = reactions catalysed by activated factor. Grey arrow = various functions of thrombin. Image source: Wikipedia, public domain.
What is the required anti-Xa level for adequate anticoagulation?
- heparin: 0.3-0.7 units/mL
- LMWH: 0.4-1.1 units/mL for SQ q 12 hr dosing. For once daily LMWH dosing, the therapeutic range is approximately 1-2 units/mL.
Prophylaxis of DVT:
There is no defined target range for prophylaxis of DVT. When anti-Xa levels are measured, the values are lower 0.45.
How do we order anti-Xa level?
On day 2 of therapy, a blood sample should be drawn 4 hours after the SQ administration of enoxaparin.
Should we monitor anti-Xa level routinely in patients on LMWH?
No. In patients with acute DVT treated with LMWH, the guideline developers recommend against routine monitoring with anti-factor Xa level measurements.
When is anti-Xa level monitoring indicated?
Occasions in which periodic monitoring of LMWH might be considered include:
- renal failure
- obesity or underweight patients
- prolonged use
- patients at high risk for bleeding or thrombosis
Oral rivaroxaban is non-inferior to standard therapy for symptomatic pulmonary embolism (PE) and DVT (NEJM, 2012).
Heparin Antifactor Xa Assay - The Laboratory Test Handbook, 5th Edition. Lexi-Comp, Cleveland, 2001; 327-358, MGH.Harvard.edu.
Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy - National Guideline Clearinghouse.
Enoxaparin (Low MW Heparin) Guidelines - ohsu.edu.
Concordance of the Activated Partial Thromboplastin Time and the Anti-Activated Factor X Assay in Monitoring Unfractionated Heparin Therapy in Critically Ill Patients - Chest.