Hypercoagulability is defined as excessive thrombin generation and is a prothrombotic state, in that the animal is predisposed to or may be suffering from thrombosis. Thrombosis is exceedingly difficult to detect clinically, particularly when it occurs within the internal microvasculature, however sudden onset of neurologic or pulmonary signs, progressive deterioration of organ function or unexpected organ dysfunction may yield clues as to its presence, particularly in animals with disorders associated with thrombosis, such as immune-mediated hemolytic anemia and protein-losing nephropathy. Sizeable organ infarcts (e.g. kidney, spleen) or large thrombi in certain vessels (e.g. vena cava) can be detected with ultrasonography and computerized tomographic pulmonary angiography can be diagnostic for pulmonary thromboembolism.
Unfortunately, there are also very few laboratory tests for hypercoagulability and they are geared at detecting excessive thrombin generation. In veterinary medicine, viscoelastic-based testing methods can detect accelerated fibrin formation or strong fibrin clots. Dogs with immune-mediated hemolytic anemia, protein-losing nephropathy and other conditions (e.g. infectious agents) have hypercoagulable profiles (Wiinberg et al 2008, Goodwin et al 2011, Goggs et al 2012,McMichael et al 2015). In the dogs with protein-losing enteropathy, the hypercoagulability did not correlate with antithrombin concentrations, suggesting that dogs may be hypercoagulable for multifactorial reasons in this syndrome (Goodwin et al 2011). However, with these methods, maximum clot strength strongly correlates with fibrinogen concentration in most studies and the results are influenced by hematocrit and platelet concentrations (Smith et al 2012, Marschner et al 2018). Some clinicians may treat patients with predisposing diseases, suggestive screening findings (e.g. high D-dimer, slightly decreased antithrombin concentrations) and hypercoagulable viscoelastic profiles with anticoagulant drugs, such as heparin or direct oral anticoagulants (e.g. rivaroxaban) or antiplatelet drugs, e.g. clopidogrel. However, to date, no studies have shown the validity of this approach. Although, in theory, tPA-induced fibrinolysis may detect resistance to fibrinolysis, there is little experimental data to support this theory.
More direct tests for hypercoagulability would include measurement of thrombin (not documented in veterinary patients), thrombin-antithrombin complexes (which has been done in animals, but is expensive and, being an ELISA, is more suitable for batch, rather than individual patient, testing) (Rimpo et al 2018), and thrombin generation potential assays (which are mostly research tools, that suffer from high analytical variability). Currently, the most available surrogates for hypercoagulability are indirect tests, such as measurement of D-dimer (thrombin is required for creation of the D-dimer epitope), AT activity (with low AT supporting increased consumption in the absence of synthetic liver failure or protein-losing conditions) and fibrinogen concentrations (hyperfibrinogemia would indicate a hypercoagulable state). One retrospective study showed that proportionally more dogs with shortened PT and/or APTT had clinical evidence of hypercoagulability, suspected pulmonary thromboembolism or high D-dimer concentrations than dogs with a normal PT and APTT. In the latter study, clinical evidence of hypercoagulability was defined as thrombosis of indwelling catheters or lines, thrombosis documented on post-mortem examination, rapid clotting of samples, or clinical suspicion of pulmonary thromboembolism, the latter was defined by high D-dimer, radiographic findings, low oxygen on blood gas analysis, or if it was written in discharge statement and the study only included 25 dogs in which TEG testing was done (Song et al 2016). However, these results should be interpreted cautiously due to the low numbers of dogs in the study, the retrospective nature and mode of selection of cases, and the fact that shortened coagulation results could be a consequence of collection. The PT and APTT are not configured to detect hypercoagulability.
