Changes

===Proteins Induced by Vitamin K Antagonism Test===

===Proteins Induced by Vitamin K Antagonism Test===

Factors II, VII, IX and X are produced in the liver as non-functional precursors which become activated by carboxylation of their glutamic acid residues in the presence of vitamin K. The inactive precursors are absent from the circulation of normal animals, as they are stored in the microsomal system of the liver. However, the absence of vitamin K results in an increase in these precursors, which spill into the circulation and become known as Proteins Induced by Vitamin K Antagonism. Concurrently, the levels of active factors II, VII, IX and X are depleted.

Factors II, VII, IX and X are produced in the liver as non-functional precursors which become activated by carboxylation of their glutamic acid residues in the presence of vitamin K. The inactive precursors are absent from the circulation of normal animals, as they are stored in the microsomal system of the liver. However, the absence of vitamin K results in an increase in these precursors, which spill into the circulation and become known as Proteins Induced by Vitamin K Antagonism (PIVKA). Concurrently, the levels of active factors II, VII, IX and X are depleted.

The PIVKA test or thrombotest is a modification of the prothrombin time. The test uses diluted plasma (which creates longer clotting times than the PT) and a specific thrombotest reagent, which is reported to be most sensitive to deficiencies in factor X. Although claims have been made in the veterinary literature that this test is sensitive to both an increase in PIVKAs (which are supposed to inhibit the reaction) as well as a decrease in the functional coagulation factors II, VII, and X (especially factors VII and X), there is no proof that PIVKAs actually inhibit the reaction. Therefore, the PIVKA test should be considered as a modified PT that detects deficiencies in factors II, VII, and X. Because the clotting times are longer than the PT, the test may be more sensitive than the PT for abnormalities in these factors, however this was not supported by a recent study measuring PIVKAs, PT and APTT in dogs with various hemostatic disorders. Furthermore, the test is only offered by certain laboratories and the turnaround time is longer than the PT, therefore measurement of PIVKAs offers no advantage over the PT. In human patients, the nonfunctional noncarboxylated coagulation proteins are measured specifically using immunologic tests.

The PIVKA test is modified version of PT that is designed to be more sensitive than PT for abnormalities in the vitamin-K dependent clotting factors. Diluted plasma is used to give longer clotting times, and a test-specific reagent is added. The PIVKA test is reported to be sensitive to both increases in PIVKAs and decreases in the functional coagulation factors II, VII, IX and X, although there is some debate as to whether PIVKAs actually inhibit the reaction. Although intended to be more sensitive than the PT for factors of interest, studies in dogs have shown that a PIVKA test offers little diagnosic advantage⁴. Additionally, only certain laboratories offer the test and the turnaround time is longer than PT.  

The PIVKA test is prolonged in vitamin K deficiency due to low vitamin K-dependent factor concentrations. This is usually due to vitamin K antagonism by anticoagulant rodenticides but can also be seen in cholestatic liver disorders, e.g. hepatic lipidosis in cats. Early studies suggested that the PIVKA test may be the first coagulation test to be prolonged after experimental administration of anticoagulant rodenticides to dogs, however no further studies have been done to support this claim. The PIVKA test, like the PT, is prolonged in some dogs with DIC and dogs with factor VII deficiency, indicating that it is not specific for vitamin K deficiency. Some authors believe that the PIVKA test is a useful guide as to which patients with liver disease and abnormal coagulation results will respond to vitamin K therapy (by normalization of the coagulation times). The PIVKA test is normal in dogs with inherited deficiencies of factors VIII, IX, and XI, and prekallikrein.

The PIVKA test is prolonged in vitamin K deficiency due to low vitamin K-dependent factor concentrations. This is usually due to vitamin K antagonism by anticoagulant rodenticides but can also be seen in cholestatic liver disorders, e.g. hepatic lipidosis in cats. Early studies suggested that the PIVKA test may be the first coagulation test to be prolonged after experimental administration of anticoagulant rodenticides to dogs, however no further studies have been done to support this claim. The PIVKA test, like the PT, is prolonged in some dogs with DIC and dogs with factor VII deficiency, indicating that it is not specific for vitamin K deficiency. Some authors believe that the PIVKA test is a useful guide as to which patients with liver disease and abnormal coagulation results will respond to vitamin K therapy (by normalization of the coagulation times). The PIVKA test is normal in dogs with inherited deficiencies of factors VIII, IX, and XI, and prekallikrein.