Des-gamma-carboxy Prothrombin (DCP), also referred to as Protein Induced by Vitamin K Absence (PIVKA-II), is a non-functional precursor of prothrombin.⁷ Prothrombin, produced by the liver, serves a critical role in normal hemostasis. Functional prothrombin contains several gamma-carboxy-glutamic acid (Gla) residues that are produced as the result of post-translational modification of glutamic acid residues mediated by vitamin K dependent gamma-glutamyl carboxylase. The formation of Gla residues can be impaired in patients with vitamin K deficiency or in patients receiving oral anticoagulant therapy. DCP lacks thrombotic activity and has been shown in multiple studies to be present in the serum of patients with HCC.^7-13

Patients who test positive for DCP often exhibit clinical features of HCC that are different from those who test postive for AFP-L3.^9-15 Published studies have indicated that DCP elevation reflects the progression of the disease and tumor diameter.^9-15 Increased DCP levels have been associated with the development of portal vein invasion (PVI), a strongly negative prognostic indicator.⁹ Patients with elevated DCP and normal AFP tend to have more advanced HCC.^10-14 Volk and coworkers showed that DCP can be particularly useful in the assessment of HCC risk in high risk patients.¹⁶

The combined use of the three biomarkers, AFP, AFP-L3% and DCP can support the discrimination between benign and malignant conditions related to primary liver disease.^10,11,14,15 DCP and AFP-L3% are considered complementary assays for assessing the risk of developing HCC.¹ When used in combination, a greater number of patients at risk of developing HCC can be identified resulting in more treatment options for a larger number of patients.¹

DCP/PIVKA-II has also been used for the assessment of the vitamin K status of newborns.¹⁸ Vitamin K deficiency may cause unexpected bleeding during the first week of life in previously healthy-appearing neonates.^18-19 This condition has been referred to as early vitamin K deficiency bleeding (VKDB) of the newborn or classic hemorrhagic disease of the newborn. Vitamin K prophylaxis (oral or parenteral) has been found to be effective in the prevention of this condition.¹⁹ Late VKDB, defined as unexpected bleeding attributable to severe vitamin K deficiency in infants 2 to 12 weeks of age, can occur in exclusively breastfed infants who have received inadaquate neonatal vitamin K prophylaxis.^18,19 Infants with intestinal malabsorption defects (cholestatic jaundice, cystic fibrosis, etc) may also have late VKDB.^18,19