Des-γ-Carboxy (Abnormal) Prothrombin as a Serum Marker of Primary Hepatocellular Carcinoma

We detected des-γ-carboxy prothrombin, an abnormal prothrombin, in the serum of 69 of 76 patients (91 per cent) with biopsy-confirmed hepatocellular carcinoma (the mean level of the abnormal prothrombin was 900 ng per milliliter). In contrast, levels of the abnormal prothrombin were low in patients with chronic active hepatitis (mean, 10 ng per milliliter) or metastatic carcinoma involving the liver (mean, 42 ng per milliliter), and undetectable in normal subjects. In five patients treated with vitamin K there was no reduction in abnormal prothrombin, indicating that its presence was not due to vitamin K deficiency. Surgical resection of tumors in two patients and chemotherapy in one patient markedly reduced abnormal-prothrombin concentrations, which later increased with recurrence of disease. Serum α-fetoprotein levels correlated poorly with abnormal-prothrombin levels. Together, the assay for abnormal prothrombin and the α-fetoprotein assay identified 64 of 76 patients with hepatoma (84 per cent). Abnormal prothrombin may be useful in the laboratory diagnosis of primary hepatocellular carcinoma. (N Engl J Med 1984; 310:1427–31.) PROTHROMBIN is a vitamin K–dependent blood-coagulation protein that is synthesized in the liver. 1 It contains γ-carboxyglutamic acid residues in its amino-terminal domain, which have the calcium-binding properties essential for its function. 2 3 4 The carboxylation of the specific amino-terminal glutamic acid residues to form γ-carboxyglutamic acid is a post-translational process of the rough endoplasmic reticulum of the normal hepatocyte. 5 , 6 The absence of vitamin K or the ingestion of vitamin K antagonists (warfarin sodium) inhibits the vitamin K–dependent carboxylase activity of the liver, and des-γ-carboxy prothrombin (abnormal prothrombin) is released into the blood. 6 7 8 9 Normal subjects have no detectable abnormal prothrombin in their blood. . . .