Alkaline phosphatase, in serum

G9. Gomez, B., Ardakani, J. J., Jenkins, D., Cerelli, M. J., Daniloff, G. Y., and Kung, V. T., Monoclonal antibody assay for measuring bone specific alkaline phosphatase in serum. Clin. Chem. 41,1560-1566 (1995). 

P3. Panigrahi, K., Delmas, P. D., Singer, E., Ryan, W., Reiss, O., et al., Characteristics of a two-site immunoradiometric assay for human skeletal alkaline phosphatase in serum. Clin. Chem. 40, 822-828 (1994). 

P9. Price, C. P., Milligan, T. P., andDarte, C., Direct comparison of performance characteristics of two immunoassays for bone isoform of alkaline phosphatase in serum. Clin. Chem. 43, 2052—2057... 

V3. Van Hoof, V. O., Martin, M., Blockx, P., Prove, A., Van Oosterom, A., etal., Immunoradiometric method and electrophoretic system compared for quantifying bone alkaline phosphatase in serum. Clin. Chem. 41, 853-857 (1995). 

Pagani F, Panteghini M. 5 -nucleotidase in the detection of increased activity of the liver form of alkaline phosphatase in serum. Clin Chem 2001 47 2046-8. 

Anderson DJ, Branum EL, O Brien JF. Liver- and bone-derived isoenzymes of alkaline phosphatase in serum as determined by high-performance affinity chromatography. Clin Chem 1990 36 240-6. 

French workers (C4, CIS) discovered in 1934 that pregnancy serum exhibits elevations in alkaline phosphatase. The origin of the enzyme has been attributed variously to maternal osteoblastic activity, to fetal osteoblastic activity, and to placenta. Following Boyer s electrophoretic studies (B38), which showed that serum exhibits a strong enzyme band in the placental region, and Posen s demonstration of heat-stable placenta-type alkaline phosphatase in serum (C13), the reasonable view now is that the placenta supplies alkaline phosphatase to the circulation. 

K20. Komer, N. H., Distribution of alkaline phosphatase in serum protein fractions. J. Clin. Pathol. 16, 195-199 (1962). 

A normochromic anemia may develop rapidly without evidence of GI blood loss, although intestinal bleeding may be contributory. Leukopenia may be reflective of a relative decrease in polymorphonuclear leukocytes. WBC counts may range from 1200 to 20,000 cells/mm . As many as one-third of the patients have elevated levels of the liver enzymes glutamic-oxaloacetic transaminase and alkaline phosphatase in serum. About 80% of patients have positive blood cultures. Bacteremia persists in about a third of cases for several weeks if not treated. Intestinal perforation, intestinal hemorrhage, thrombophlebitis, toxemia with circulatory collapse, encephalopathy, and pneumonia all contribute to a fatality rate of 1 % to 2%. Without treatment, mortality may be 10%. ... 

The measurement of alkaline phosphatase in serum or plasma constitutes one of the most widely employed tests in the clinical chemistry laboratory (Table 1). The subject has been repeatedly reviewed in recent years (FIO, Fll, K5, Mc3, P24, P29). An attempt will therefore be made in this article to list some of the more recent references and to indicate under what circumstances serum alkaline phosphatase measurements are of clinical value. 

Brandt, K., Cathcart, E. S., and Cohen, A. S., A clinical analysis of the cause and prognosis of forty-two patients with amyloidosis. Am. ]. Med. 44, 955-969 (1968). Brante, G., Kaijser, K., and Ockerman, P. A., Glycogenosis Type I (lack of glucose-6-phosphatase) in four siblings. Acta Paediat. Scand. Suppl. 157, 1-28 (1964). Brensilver, H. L., and Kaplan, M. M., SigniRcance of elevat liver alkaline phosphatase in serum. Gastroenterology 68, 1556-1562 (1975). 

Tietz, N. W., Woodrow, D., and Woodrow, B., A comparative study of the Bodansky and the Bessey, Lowry and Brook methods for alkaline phosphatase in serum. Clin. Chim. Acta 15, 365-367 (1967),... 

The activity of alkaline phosphatase in serum is elevated above normal in a variety of different bone diseases, as well as biliary obstruction and some other liver diseases. Measurement of alkaline phosphatase activity in serum can thus give useful information about these conditions. It is especially useful for diagnosis of preclinical rickets and osteomalacia (section 11.3.4). 

Pankaj B, Kamik AB, Venkatakrishna-Bhatt H. 1986. Influence of oral lead acetate on serum transaminases and alkaline phosphatase in albino rats. Proc Nati Acad Set India Sect B (Biol Sci) 56 1-4. 

Hepatotoxicity A few cases of reversible clinical hepatotoxicity have occurred in some patients, asymptomatic rises in serum alkaline phosphatase or serum transaminase levels have been observed. If anorexia, weight loss or pruritus develop in patients on allopurinol, evaluation of liver function should be part of their diagnostic workup. Perform periodic liver function tests during early stages of therapy. 

Pre-wintering migration. Metabolism is adjusted to a stable state lipid accumulation and increase in protein are at a standstill the activity of alkaline phosphatase in the scales, which regulates the development of sclerites, decreases markedly the concentration of protein in the blood serum remains stable. During the wintering period, the metabolic activity of the population declines considerably. Lipid reserves decline steadily and tend to exhibit an increased degree of unsaturation in these warm-water fish because of the lower... 

Spooner, F.J., Smith, D.H., Bedford, D., Beck, P.R. Serum gaimna-glutamyltransferase and alkaline phosphatase in rheumatoid arthritis. X Clin. Pathol. 1982 35 638-641... 

Cholestasis has been reported in infants treated with amphotericin for systemic Candida infections (SEDA-14, 230). Most of the above reports were incidental, and amphotericin cannot be regarded as a known cause of liver damage. This does not necessarily also apply to liposomal amphotericin and other lipid formulations. Therapy with L-Amb, AmBisome was associated with a rise in alkaline phosphatase in over a third of children treated with AmBisome (93) and with hepatic dysfunction in a little under 20% of adolescents and adults. In a small retrospective study, ABLC was withdrawn in 27% of patients because of rises in serum bilirubin and alkaline phosphatase, a finding confirmed in a larger prospective study. Cholestasis has also been observed with ABCD, in contrast to reports that L-AmB does not increase transaminases (5). 

Mexiletine caused increases in the serum activities of aspartate transaminase, alanine transaminase, and alkaline phosphatase in a few patients (8). 

Given the above preclinical observations, patients in a clinical study were monitored closely during treatment (including measurement of testosterone, luteinizing hormone, follicle-stimulating hormone levels, alkaline phosphatase, and serum vitamin A concentrations). This phase I clinical study of TAG-101 was conducted to determine the safety, toxicity, and pharmacokinetics of this agent in patients with advanced cancer. Currently, the drug is in a phase I/II clinical trial for advanced hepatocellular carcinoma. 

Figure 21-5 A, Poiyacrylam id e-gel electrophoresis of bone and liver alkaline phosphatases in human serum. Left, Mixture of two sera containing, respectively, entirely bone phosphatase and entirely liver phosphatase. Right, Mixture of the same two sera after each has been treated with neuraminidase for 0 minutes at 37 C.The anodai direction is downward.The more anodal zone is liver phosphatase. B, Densltometric scans of electrophoretic patterns shown in A. Broken line, Scan of mixture of untreated sera solid line, scan of mixture of sera treated briefly with neuraminidase. The anode is to the left. (From Moss DW, Edwords RK. In proved electrophoretic resolution of bone and liver alkaline phosphatases resulting from partial digestion, with neuraminidose. Clin Chim Acta 1984 143 i 77-82.) ...

Figure 47-18 Algorithm for using elevated activities of serum alkaline phosphatase in the diagnosis of liver disease in adults.

Farley JR, Hall SL, Ilacas D, Orcutt C, Miller BE, Hill CS, Baylink DJ. Quantification of skeletal alkaline phosphatase in osteoporotic serum by wheat germ agglutinin precipitation, heat inactivation and a two-site iramunoradiometric assay. Clin Chem 1994 40 1749-59. 

HUl C, Cerrito M, Grafstein E, Rao S, Wolfert R. Development of the BAP Tandem-R assay for the specific detection of bone alkaline phosphatase in human serum. CHn Chem 1991 37 1019. 

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