Abnormal Prothrombin (PIVKA-II) Expression in Canine Tissues as an Indicator of Anticoagulant Poisoning.

Lorella Maniscalco,Elena Torres,Marta Ferrero,Francesca Rossi,Giuseppina Abbamonte,Federica Ostorero,Katia Varello,Elena Bozzetta,Simona Zoppi

doi:10.3390/ani11092612

Abstract

Simple SummaryPIVKA-II is an aberrant form of vitamin K that has been demonstrated to be increased in human coagulation disorders and in some neoplastic diseases. In veterinary medicine, PIVKA-II levels have been demonstrated to be useful for distinguishing anticoagulant poisoning from other coagulopathies. In forensic pathology, there is the need to distinguish malicious poisoning from other causes of death and, in some cases, identifying poisoned dogs from dogs that died as a result of other coagulative disorders can be challenging. This study evaluated the usefulness of the immunohistochemical expression of PIVKA-II in hepatic and renal tissues in order to identify patients with coagulative disorders due to clinical condition or the ingestion of anticoagulants substances.PIVKA-II is an aberrant form of vitamin K that has been demonstrated to be increased in human coagulation disorders and in some neoplastic diseases. In veterinary medicine, PIVKA-II levels have been demonstrated to be useful for distinguishing anticoagulant poisoning from other coagulopathies. In forensic pathology, there is the need to distinguish malicious poisoning from other causes of death and, in some cases, identifying poisoned dogs from dogs that died as a result of other coagulative disorders can be challenging. In this study, dogs that suddenly died underwent necropsy, histological examination, and toxicological analysis to establish cause of death. PIVKA-II immunohistochemical expression was evaluated on hepatic and renal tissues, and on neoplastic lesions when present. A total of 61 dogs were analyzed and anticoagulant substances were identified in 16 of the 61. Immunolabelling for PIVKA-II was observed in 27 of 61 cases in the liver and in 24 of 61 cases in the kidneys. Among the poisoned dogs, the PIVKA-II expression was present in the liver in 15 of 16 cases and in the kidneys in 16 of 16. Neoplastic lesions represented mainly by haemangiosarcomas were negative. This study highlights how the immunohistochemical expression of PIVKA-II in hepatic and renal tissues can be useful to identify patients with coagulative disorders due to clinical condition or the ingestion of anticoagulants substances.

Highlights

In human medicine the PIVKA-II expression in tissues has been evaluated for its importance as a prognosticator in cancer, to the best knowledge of the authors, PIVKA-II has not been previously investigated in the veterinary field, so the aim of this work is to consider the PIVKA-II expression in canine tissues as a useful diagnostic tool to distinguish whether the cause of death was as a result of anticoagulant poisoning or some other conditions
Gross lesions suggestive of a coagulative disorder were observed in 24 cases (39.34%), of which 16 (26.23%) showed positive results for anticoagulant substances
Since the 19900 s, PIVKA-II has been widely used as a human marker of hepatocellular carcinoma, demonstrating that an aberrant form of vitamin K can be produced by a lack of vitamin K induced by anticoagulant administration, coagulation disorders, and neoplastic modification of the hepatic tissue [17,18,19,20]

Summary

Introduction

Vitamin K, discovered by Dane Henrik Dam in 1930, is an essential cofactor in the carboxylation of hepatic coagulation factors (F), i.e., prothrombin (FII), FVII, FIX, and FX; proteins C, S, Z, and M; and several extrahepatic vitamin-K-dependent proteins [1]. Kis an essential cofactor for the γ-carboxylation of key glutamic acid residues in blood clotting proteins by vitamin K-dependent carboxylase [2]. Acute vitamin K deficiency is classically characterized by deranged coagulation because of insufficiency of vitamin Kdependent coagulation factors, but it can be induced by action of vitamin K antagonists such as warfarin, used therapeutically as oral anticoagulants. Vitamin K is converted from the active form to vitamin K 2,3-epoxide, which must be recycled to the active form by vitamin K epoxide reductase (VKOR) to maintain the coagulation cycle

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