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Subject: Heparin Anti-Xa (Low Molecular Weight Heparin)
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The a-Xa assay measures the functional plasma level of various heparins used for the prevention or therapy of thromboembolic events. It is not a direct measurement of heparin. The assay measures heparin's effectiveness when bound to antithrombin in interfering with the physiologic effect of factor Xa on factor II.
The effectiveness of therapy with unfractionated heparin (UH) and its various derivatives (low molecular weight heparins [LMWH], fondaparinux) and new anti–factor Xa anticoagulants such as rivaroxaban. The quantitative effects of each of these agents are useful tools for determining the efficacy of the therapy. In most laboratories, a chromogenic assay is being used. While the assay in general is applicable to all the drugs mentioned above, specific calibrators are needed for each type of drug separately, to allow the production of specific curves on which the activity is determined precisely. Calibrators for rivaroxaban are presently being developed.
The assay is not generally used for monitoring UH therapy, because the routinely used PTT is highly sensitive to the activity of this drug, and evidence-based guidelines have established its use. In the presence of a baseline prolonged PTT (such as in patients with lupus anticoagulant, “contact factor” deficiency), the a-Xa assay may replace the use of PTT. Similarly, in patients with very high levels of factor VIII, the PTT may underestimate the degree of anticoagulation produced by UH, and the plasma a-Xa will provide a more accurate measurement of the degree of anticoagulation.
Since UH is used intravenously in most cases, once a steady infusion has been established, the time of obtaining the sample is not relevant.
Obtaining a-Xa assay is not necessary in most cases when using LMWH, since fixed doses are given for either prophylactic or therapeutic use, based on body weight. There are situation when monitoring with this assay is necessary, because the body weight is not entirely representative of the drug's distribution or efficacy: in patients with impaired renal function, pregnancy, obesity, cachexia, infants, and burns (rapid body fluids shifts).
Reference ranges for a-Xa levels depend on the heparin type, dose, schedule, and indications. In the absence of heparin therapy, the a-Xa concentrations should be undetectable.
Intravenous infusion of UH: 0.30–0.70 IU/mL.
LMWH: 0.40–1.10 a-XaU/mL for twice daily dosing or 1.00–2.00 a-FXaU/mL for once daily dosing. Blood should be drawn as a “peak” test, about 4 hours following the subcutaneous injection. Random or “through” a-Xa tests may be performed when there is concern of LMWH accumulation in patients with impaired renal function.
Prophylactic use of LMWH: 0.20–0.50 a-XaU/mL.
Great attention must be paid in preparing the plasma to be tested in order to eliminate platelet contamination (platelets when activated release platelet factor 4, a potent antiheparin protein). Careful and adequate centrifugation is necessary.
Spuriously low results may be seen in patients with antithrombin deficiency.