Deamidation of glutamine by increased plasma gamma-glutamyltransferase is a source of rapid ammonia formation in blood and plasma specimens

Fonseca-Wollheim, F. da

doi:10.1093/clinchem/36.8.1479

Cited by 57 publications

(22 citation statements)

References 8 publications

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“…31,32 It should also be noted here that there are some ammonia-producing and NADH-consuming side-reactions that result in decreasing absorbance at 340 nm independently of FXIIIa activity. [33][34][35][36] The effect of these side-reactions varies from plasma to plasma and corresponds with 2 to 15% of average normal FXIII activity, which is a serious limitation in the assay specificity. 36 Such an overestimation of FXIII activity, which does not usually cause a problem in the normal range, might produce falsely high levels of FXIII in FXIII-deficient patients, thereby giving misleading information on the severity of FXIII deficiency and on the effectiveness of any replacement therapy.…”

Section: Ammonia-release Assaysmentioning

confidence: 99%

Factor XIII Deficiency

Karimi

Bereczky

Cohan

et al. 2009

Semin Thromb Hemost

188

209

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Factor XIII (FXIII) is a tetrameric zymogen (FXIII-A (2)B (2)) that is converted into an active transglutaminase (FXIIIa) by thrombin and Ca (2+) in the terminal phase of the clotting cascade. By cross-linking fibrin chains and alpha (2) plasmin inhibitor to fibrin, FXIIIa mechanically stabilizes fibrin and protects it from fibrinolysis. Severe deficiency of the potentially active A subunit (FXIII-A) is a rare but severe hemorrhagic diathesis. Delayed umbilical stump bleeding is characteristic, and subcutaneous, intramuscular, and intracranial bleeding occurs with a relatively high frequency in nonsupplemented patients. In addition, impaired wound healing and spontaneous abortion in women are also features of FXIII deficiency. The extremely rare B subunit deficiency results in milder bleeding symptoms. FXIII concentrate is now available for on-demand treatment and primary prophylaxis. A quantitative FXIII activity assay is recommended as a screening test for the diagnosis of FXIII deficiency. For classification purposes, FXIII-A (2)B (2) antigen in the plasma is first determined, and if decreased, further measurement of the individual subunits is recommended in the plasma and FXIII-A in platelet lysate. Analytical aspects of FXIII activity and antigen assays are discussed in this article. There are no hot-spot mutations in the F13A1 and F13B genes, and the majority of causative mutations are missense/nonsense point mutations.

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Section: Ammonia-release Assaysmentioning

confidence: 99%

Factor XIII Deficiency

Karimi

Bereczky

Cohan

et al. 2009

Semin Thromb Hemost

188

209

View full text Add to dashboard Cite

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“…This applies even more to blood from patients with liver disease because increased ␥-glutamyl transferase activity, a frequent observation in cirrhotic patients, has been associated with increased enzymatic hydrolysis of glutamine leading to artefactual increased ammonia levels. 22 Therefore, it is advised that blood be analyzed within 15 minutes of collection. 18 In the study by Ong et al, 13 however, analysis was performed somewhat later (within 30 min).…”

Section: Commentsmentioning

confidence: 99%

Blood Ammonia Determination in Cirrhosis: Still Confusing After All These Years?

Yurdaydın¹

2003

Hepatology

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Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med 2003;114:188-193. (Reprinted with permission from Excerpta Medica, Inc.) PURPOSE: Because the correlation between ammonia levels and the severity of hepatic encephalopathy remains controversial, we prospectively evaluated the correlation in 121 consecutive patients with cirrhosis. METHODS: The diagnosis of hepatic encephalopathy was based on clinical criteria, and the severity of hepatic encephalopathy was based on the West Haven Criteria for grading of mental status. Arterial and venous blood samples were obtained from each patient. Four types of ammonia measurements were analyzed: arterial and venous total ammonia, and arterial and venous partial pressure of ammonia. Spearman rank correlations (r s ) were calculated. RESULTS: Of the 121 patients, 30 (25%) had grade 0 encephalopathy (no signs or symptoms), 27 (22%) had grade 1, 23 (19%) had grade 2, 28 (23%) had grade 3, and 13 (11%) had grade 4 (the most severe signs and symptoms). Each of the four measures of ammonia increased with the severity of hepatic encephalopathy: arterial total ammonia (r s ‫؍‬ 0.61, P < .001), venous total ammonia (r s ‫؍‬ 0.56, P < .001), arterial partial pressure of ammonia (r s ‫؍‬ 0.55, P < .001), and venous partial pressure of ammonia (r s ‫؍‬ 0.52, P < .001). CONCLUSION: Ammonia levels correlate with the severity of hepatic encephalopathy. Venous sampling is adequate for ammonia measurement. There appears to be no additional advantage of measuring the partial pressure of ammonia compared with total ammonia levels.

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“…[1][2][3][4][5][6][7] The sources of the increase in plasma ammonia concentration in vitro reportedly include deamination reactions in erythrocytes and platelets, and the deamidation of plasma glutamine by γglutamyltransferase (γ-GT). 4,6,[8][9][10] While these studies demonstrated the clinical importance of plasma ammonia specimen integrity, many of these studies were performed with blood collection techniques and analytical methods that are no longer in use. In some cases, blood was collected directly into Erlenmeyer flasks, evacuated glass tubes, or via syringe into dipotassium EDTA.…”

Section: Introductionmentioning

confidence: 99%

Blood Ammonia Stability Revisited

2015

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The instability of ammonia in whole blood has challenged clinical laboratory scientists to develop specimen collection and handling methods that produce reliable results for plasma ammonia concentration. Thirty-eight outpatients' plasma ammonia concentrations were measured after heparinized whole blood specimens from each subject were held for 5, 15, and 30 minutes at room temperature and "on-ice". The plasma ammonia concentration from whole blood maintained "on-ice" for 5 minutes was designated the "reference value". Plasma ammonia concentrations from whole blood maintained "on-ice" for 15 or 30 minutes prior to processing were not significantly different from the reference values (15 min., p~0.196; 30 min., p~0.512). Plasma ammonia concentrations from whole blood maintained at room temperature for 5, 15 and 30 minutes prior to processing were also not significantly different from the reference values (p~0.961, 0.610, and 0.948, respectively). These results suggest that reliable plasma ammonia concentrations may be obtained from heparinized whole blood maintained at room temperature for up to 30 minutes.

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Deamidation of glutamine by increased plasma gamma-glutamyltransferase is a source of rapid ammonia formation in blood and plasma specimens

Cited by 57 publications

References 8 publications

Factor XIII Deficiency

Factor XIII Deficiency

Blood Ammonia Determination in Cirrhosis: Still Confusing After All These Years?

Blood Ammonia Stability Revisited

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