On the Presence of Ferritin in the Peripheral Blood of Patients With Hepatocellular Disease

Abstract

An elevated serum iron is commonly found in patients with infectious hepatitis (1-4) and evidence has been presented (5, 6) that acute hepatocellular necrosis, regardless of its etiology, is invariably accompanied by a rise in serum iron. A close time relationship between elevation of the serum iron and actual disintegration of liver cells has been found (6), and the hyperferremia has been attributed to a release of storage iron from the dying liver cells. As the iron is largely stored in the liver as ferritin, it was of interest to investigate whether ferritin is released into the peripheral blood of patients with acute hepatocellular disease, while it could not be demonstrated in the blood of normal individuals (7).Mazur, Shorr, and Baez (8-10) have reported the presence of VDM, which is said to be identical with ferritin, in the peripheral blood in several conditions including hepatic cirrhosis, congestive heart failure and shock. The concentrations of this vasoactive material were so minute that their detection required the use of the mesoappendix bioassay. We were, in this study, concerned with a possible relationship between serum iron rise and the release of ferritin iron from the necrotic liver cells. METHODSCrystalline ferritin-apoferritin was prepared from human liver tissue (autopsy material) according to the method of Granick (7). The crude ferritin was recrystallized five times with CdSO4, reprecipitated at 50 per cent saturation with (NH4),SO4, and dialyzed against tap water for 24 hours. At that time the preparation was usually free of NH4 ions.The antiserum was prepared according to the procedure of Mazur and Shorr (8). Rabbits were injected intravenously with aluminum precipitated human ferritin over a period of four weeks. Each animal received a total of 4.4 mg. of antigen nitrogen, and thereafter booster injections of 0.15 mg. of antigen nitrogen. The antisera were chilled, sharply centrifuged and pooled. The antiferritin titer of the antiserum was determined by adding known amounts of ferritin dissolved in human serum to one cc. of the 1: 10 diluted antiserum. The mixture was incubated for one hour at 370 C. and stored for three days at 40 C. The tubes were then centrifuged, the precipitate washed with chilled saline, and the iron and nitrogen in the precipitate were measured. The supernatant was tested for excess of antigen or antibody.The iron content of ferritin was measured by Scott's method (11). Other iron methods employed were the methods of Wong (12), of Barkan and Walker (13) and a modification of the latter as described below.The ferritin determination in the blood of patients was carried out in the following manner: The blood was collected in iron free tubes and the serum was sharply centrifuged to remove all red cells. Four cc. of this serum was added to 0.3 of antiserum, to 0.3 of 1: 3 diluted antiserum, and to 0.3 cc. of normal rabbit serum, respectively.After one hour of incubation at 370 C. and three days' storage at 4°C., the tubes were centrifuged. When ferritin was present...

Extremely High Ferritinemia Associated with Haemophagocytic Lympho Histiocytosis (HLH)

“…It can be elevated in wide range of conditions such as malignancy, infection, septic shock, inflammation and chronic iron overload syndrome. It plays a role as acute phase reactant [2][3][4][5][6][7].…”

Serum Ferritin Iron, a New Test, Measures Human Body Iron Stores Unconfounded by Inflammation

“…Measurement of serum ferritin protein levels is generally accepted as the best noninvasive means to determine body iron stores, but only if serum level of ferritin protein and serum level of iron run in the same direction. Elevations in serum ferritin protein levels may occur without elevation of iron stores in acute inflammatory conditions or in liver disease or cancer [15][16][17][18][19][20][21] where serum ferritin protein is usually >400 ng/ml. Serum ferritin protein levels >400 ng/ml define iron overload in most clinical laboratories, but, in fact, such interpretation requires confirmation by finding a high percentage of saturation with iron of iron BC (transferrin).…”

Arvelig hemokromatose gjennom 150 år

“…Til å begynne med var ferritin bare mål-bart i serum etter akutt leversykdom med cellenekrose (20), men etter utviklingen av en sensitiv immunologisk analysemetode i 1972, kunne man også måle ferritin i serum fra friske individer, og det ble vist at nivået var proporsjonalt med størrelsen på jernlageret i lever og beinmarg (21).…”