Inhibitors

The most commonly used (and available) tests for inhibitors are measurement of antithrombin and protein C activity. Tests for other inhibitors, such as alpha2-antiplasmin, protein Z, protein S, and heparin cofactor II, are either not available, have not been validated for use in animals or are used for research purposes by specific institutions.

The presence of acquired inhibitors of coagulation (e.g. lupus anticoagulants, anti-factor VIII antibodies) can be suspected when coagulation tests (usually the APTT) shorten when the patient sample is diluted with sterile saline. In patients with factor deficiencies, the APTT will lengthen due to further dilution of the factors, whereas the APTT will shorten in patients with inhibitors due to dilution of the inhibitors. Specific assays for such inhibitors include Bethesda assays for anti-factor antibodies and modified phospholipid assays for measurement of lupus anticoagulant. There are also assays for therapeutic monitoring of anticoagulants, such as heparin.

Other tests (that include inhibitors) are those that measure factor-inhibitor complexes. High concentrations of thrombin-antithrombin complexes are a sensitive and specific indicator of thrombin activation, however the test has only been validated and used in specific research projects. Similarly, high concentrations of plasmin-antiplasmin complexes are a good indicator of plasmin activation, however once again this is not a readily available test. Both thrombin-antithrombin and plasmin-antiplasmin complexes are high in human patients with DIC and these tests could be useful in animals, however none are currently commercially available for veterinary use.

 

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