Evaluation of plasma protein C activity for detection of hepatobiliary disease and portosystemic shunting in dogs

Abstract

Combining PC with routine tests improved recognition of PSS, hepatic failure, and severe hepatobiliary disease and signified a grave prognosis when coupled with hyperbilirubinemia and low antithrombin activity in hepatic failure. Protein C activity can help prioritize tests used to distinguish PSVA from MVD and sensitively reflects improved hepatic-portal perfusion after PSVA ligation.

Protein C Activity in Dogs: Adaptation of a Commercial Human Colorimetric Assay and Evaluation of Effects of Storage Time and Temperature

“…Nevertheless, our findings and those of others indicate that Agkistrodon c. contortrix venom works sufficiently on canine samples to enable the measurement of protein C activity if pooled canine plasma is used to calibrate the assay. Using this approach, our preliminary reference values of 80–115%, based on minimum and maximum values because of the relatively small sample size, are consistent with those reported by Toulza et al (75–135%) [4] and Bauer et al (76–119%) [4, 11]. The precision of the assay was acceptable: our coefficients of variation were lower than reported by others [4, 8, 11] and met the performance goals for diagnostic application in humans [4, 8, 11, 16].…”

“…Many conditions are recognized to cause decreased protein C activity in people, including liver disease, sepsis, and inflammation [2, 3]. In dogs, protein C activity is decreased with a variety of hepatobiliary diseases, especially hepatic failure and congenital portosystemic shunts, and has been used to differentiate congenital portosystemic shunts from microvascular dysplasia secondary to portal hypoplasia [4–6]. Protein C activity is also decreased in dogs with sepsis, congestive heart failure, and naturally acquired food-borne aflatoxicosis [7–10].…”

“…Several reports cite the use of pooled canine plasma for assay calibration, instead of a commercial human standard; these studies have been performed using various combinations of instruments and assay reagents, including clotting-based and colorimetric (chromogenic substrate-based) assays [4, 6, 8, 9, 11]. Other reported variations in methodology include different activation times, anticoagulant concentrations, and centrifugation settings for separating plasma [8, 11, 12].…”

Reference Intervals and Method Optimization for Variables Reflecting Hypocoagulatory and Hypercoagulatory States in Dogs using the STA Compact® Automated Analyzer

“…11 Previous investigations in dogs have proven that functional protein C assays will detect significant differences between protein C concentrations in patients with various diseases including sepsis 11,12 and portosystemic shunts. 46 Regarding the resistance against activated protein C, a reference interval for APC ratio has not been established in dogs. In humans, an APC ratio ,2.1 sec has been considered abnormal, 45 which was comparable with the results in dogs of the present study.…”

“…23 The STA CompactH is a completely automated bench-top hemostasis analyzer capable of performing clotting, chromogenic, and immunological assays in random access mode. This instrument has been used previously with canine samples to measure routine coagulation parameters, AT, protein C (chromogenic assay), 11,12,46 and fibrin D-dimers. 3,13 The STA-RotachromH heparin test, run on the STA coagulation analyzer, has been validated for use with blood plasma of 12 healthy dogs and 10 dogs with immune-mediated hemolytic anemia (IMHA) to determine anti-FXa activity when monitoring heparin therapy.…”