Laboratory Monitoring

Laboratory monitoring of the plasma anti-Xa activity response is not required for routine use of danaparoid for thrombosis prophylaxis or treatment. However, it is recommended in the following clinical settings: (1) patients with substantial renal impairment; (2) children or adults with unusually low or high body weight; (3) patients with life- or limb-threatening thrombosis; (4) patients with high bleeding risk; and (5) critically ill or unstable patients.

All pharmacokinetics and recommended plasma anti-Xa activity responses are based upon an amidolytic assay. Since danaparoid, unlike UFH and the LMWHs, does not significantly prolong the aPTT, prothrombin time/INR, or ACT, except at very high doses, these assays cannot be used for monitoring. The lack of binding to plasma proteins means that danaparoid anti-Xa levels will be overestimated if a LMWH standard curve is used. Further, there are differences in the stated therapeutic range among these various anticoagulants (UFH, 0.2-0.4U/mL by protamine titration; UFH, 0.3-0.7 anti-Xa U/mL; LMWH, 0.6-1.0 U/mL; danaparoid, 0.5-0.8 anti-Xa U/mL) (Hirsh et al., 1998; Laposata et al., 1998; Warkentin et al., 1998). This means that for any assay of danaparoid plasma anti-Xa levels, the standard calibration curve must be constructed using danaparoid, and not UFH or even LMWH (Laposata et al., 1998).

The 100% bioavailability of danaparoid also allows predictable plasma levels after both sc or iv injection, but in some clinical treatment settings, it might be advisable to aim for a lower anti-Xa level (e.g., about 0.3 U/mL for a patient judged to have a high risk of bleeding); sometimes, a higher target anti-Xa level should be sought (e.g., about 1.0U/mL for a patient with life- or limb-threatening venous or arterial thrombosis or clotting during CRRT).

The amidolytic anti-Xa assay uses a chromogenic substrate (i.e., a method similar to that performed for monitoring LMWH treatment). A standard reference curve must be constructed using various dilutions of danaparoid (e.g., 1.6, 1.0, 0.5, 0.3, and 0U/mL danaparoid, diluted in pooled normal platelet-poor plasma). Control plasma samples are prepared by adding known quantities of danaparoid to normal pooled plasma aliquots (assuming 100% recovery of the known quantity of danaparoid added) in three different concentrations approximating treatment situations (e.g., 0.2, 0.7, and 1.25 U/mL, corresponding to low-, mid-, and high-control danaparoid levels). Aliquots stored at —70°C are stable for several years if used only once, without re-freezing and re-thawing.

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