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

Olivier Toulza DVM1, Sharon A. Center DVM, DACVIM2, Marjory B. Brooks DVM, DACVIM3, Hollis N. Erb DVM, PhD4, Karen L. Warner5, and Wendy Deal DVM6
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  • 1 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 2 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 3 Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 4 Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 5 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
  • | 6 Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.

Abstract

Objective—To determine the diagnostic value of protein C (PC) for detecting hepatobiliary disease and portosystemic shunting (PSS) in dogs.

Design—Prospective study.

Animals—238 clinically ill dogs with (n = 207) and without (31) hepatobiliary disease, including 105 with and 102 without PSS.

Procedures—Enrollment required routine hematologic, serum biochemical, and urine tests; measurement of PC activity; and a definitive diagnosis. Total serum bile acids (TSBA) concentration and coagulation status, including antithrombin activity, were determined in most dogs. Dogs were grouped into hepatobiliary and PSS categories. Specificity and sensitivity were calculated by use of a PC cutoff value of 70% activity.

Results—Specificity for PC activity and TSBA concentrations was similar (76% and 78%, respectively). Best overall sensitivity was detected with TSBA, but PC activity had high sensitivity for detecting PSS and hepatic failure. Protein C activity in microvascular dysplasia (MVD; PC ≥ 70% in 95% of dogs) helped differentiate MVD from portosystemic vascular anomalies (PSVA; PC < 70% in 88% of dogs). A receiver operating characteristic curve (PSVA vs MVD) validated a useful cutoff value of < 70% activity for PC.

Conclusions and Clinical Relevance—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.

Abstract

Objective—To determine the diagnostic value of protein C (PC) for detecting hepatobiliary disease and portosystemic shunting (PSS) in dogs.

Design—Prospective study.

Animals—238 clinically ill dogs with (n = 207) and without (31) hepatobiliary disease, including 105 with and 102 without PSS.

Procedures—Enrollment required routine hematologic, serum biochemical, and urine tests; measurement of PC activity; and a definitive diagnosis. Total serum bile acids (TSBA) concentration and coagulation status, including antithrombin activity, were determined in most dogs. Dogs were grouped into hepatobiliary and PSS categories. Specificity and sensitivity were calculated by use of a PC cutoff value of 70% activity.

Results—Specificity for PC activity and TSBA concentrations was similar (76% and 78%, respectively). Best overall sensitivity was detected with TSBA, but PC activity had high sensitivity for detecting PSS and hepatic failure. Protein C activity in microvascular dysplasia (MVD; PC ≥ 70% in 95% of dogs) helped differentiate MVD from portosystemic vascular anomalies (PSVA; PC < 70% in 88% of dogs). A receiver operating characteristic curve (PSVA vs MVD) validated a useful cutoff value of < 70% activity for PC.

Conclusions and Clinical Relevance—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.

Contributor Notes

Dr. Toulza's present address is 1163 rue de Naulas, 12100 Millau, France.

Address correspondence to Dr. Center.