How to Interpret Serum Amyloid A Concentrations

The role of the clinical veterinarian encompasses many features of medical practice, but in many cases starts with a simple dichotomization: is this animal normal or abnormal? This can include the question, “is it lame or sound,” but often also includes, “is it sick or well?” A thorough history and physical examination will often reveal how to stratify the patient, but in cases of subtle disease especially for horses in high level competition, mild and early signs of infection and inflammation may be occult yet significant. A reliable test for infection or inflammation, therefore, can have an extremely valuable place in the clinician’s armamentarium. Good tests allow for some degree of quantification both to allow the practitioner to assess the severity of the process and also to follow and document its response to therapy and track its resolution over time. The earliest of these tools was rectal temperature, in which fever signified a secondary indicator of increased cytokines such as tumor necrosis factor (TNF)and interleukin (Il)-1. However, over the past century, blood analysis has allowed us to quantify multiple inflammatory markers including the acute phase proteins such as fibrinogen, haptoglobin, 1-acid glycoprotein, C-reactive protein (mainly in humans), serum amyloid A (SAA), and many others, as well as secondary indicators such as white blood cell count and serum iron levels. Of these, fibrinogen has probably been the most heavily relied on for horses. It can be easily and inexpensively measured, but may be confounded by in vitro preanalytical microclot formation. However, its concentration only slowly increases in the 24 hours after induction of inflammation and often does not peak until 48 hours. In addition, there is often only a small increase (often only a 1–2-fold difference) from baseline, and thus mild inflammation cannot reliably be distinguished from normal values. Nonetheless, any method that detects inflammation in the horse probably must outperform fibrinogen in one or more of these factors: accuracy, ease of interpretation, cost, and ease of use. SAA is the major acute-phase protein of the horse (and most other mammals), and is produced predominantly by the liver as a systemic manifestation of the body’s response to inflammation. It exists in equine plasma as one of three isoforms of apolipoprotein and is complexed to high-density lipoprotein in circulating blood. First investigated in horses in the 1980s, its clinical use as a marker of inflammation is probably eclipsed by fibrinogen as a function of assay availability rather than diagnostic inferiority. The advantages of SAA over fibrinogen include that it has both low/undetectable constitutive expression in normal animals but reaches levels of 100-1000-fold baseline values in clinical disease