Monitoring of heparin therapy is important to ensure appropriate dosing. Guidelines for target heparin doses are extrapolated from the human literature and may not be applicable to animals. Most studies on therapeutic heparin monitoring have been done in dogs (Brooks, 2004). We can assess for the presence of heparin in the sample by its ability to bind to antithrombin, which then inhibits thrombin and activated factor Xa. So in essence, we are not measuring heparin directly but indirectly through AT activity. The activity of antithrombin can be measured through prolongation of the activated partial thromboplastin time (APTT) and inhibition of factor Xa by AT, which is also called anti-FXa activity. The latter is performed in preference to the APTT because it is more accurate, but anti-FXa testing is only offered by some laboratories. Anti-FXa activity can be used to monitor treatment with fractionated (low molecular weight) or unfractionated heparin, but the APTT can only be used to monitor unfractionated heparin (which inhibits thrombin more than FXa).
Method of measurement
- APTT-based testing: This can only be done for unfractionated heparin and relies on the routine APTT.
- Anti-FXa activity: This is done for unfractionated and fractionated heparin. A standard amount of bovine factor Xa is added to the patient plasma, along with a chromogenic substrate that will be cleaved by factor Xa. If factor Xa is inhibited by heparin (through antithrombin), the substrate will not be cleaved. Thus the anti-FXa activity is inversely proportional to cleavage of the substrate. Results are expressed as FXa inhibitory units (in U/ml).
- APTT-based testing: For unfractionated heparin, the target therapeutic range is an APTT that is prolonged 1.5-2.5x normal.
- Anti-FXa activity: Target values are 0.35-0.7 U/ml for unfractionated heparin and 0.5-1.0 U/ml for low molecular weight heparin in dogs (Brooks, 1994).
- Comparative Coagulation Laboratory in the Animal Health Diagnostic Center at Cornell University: Information on fibrinogen testing.