The vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) are produced in the liver as nonfunctional precursors. These precursors are activated, in the presence of vitamin K, by carboxylation of their glutamic acid residues. This is achieved with the aid of an enzyme called gamma glutamyl carboxylase. Carboxylation of these amino acid residues increases the negative charge of the protein and allows these coagulation factors to bind calcium, which is essential for the adhesion of these factors to platelet phosphatidylserine and form highly active enzymatic complezes (which is necessary for fibrin formation). In the absence of vitamin K, there is an increase in these non-fucntional factors in the circulation, as well as a depletion of the functional activated coagulation factors. The inactive precursors that accumulate in the circulation are called Proteins Induced by Vitamin K Antagonism or Absence. |
The PIVKA test or thrombotest is actually 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 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. The test has gone out of favor in veterinary medicine and is rarely used anymore. In human patients, the nonfunctional noncarboxylated coagulation proteins are measured specifically using immunologic tests.
The PIVKA test is prolonged in vitamin K deficiency due to low concentrations of active vitamin K-dependent factors. Vitamin K deficiency 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.
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