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Fresh frozen plasma contains free asparagine and may replace the plasma asparagine pool during L-asparaginase therapy

Leukemia volume 22, page 1290 (2008)Cite this article

The antileukemic effect of the enzyme asparaginase (L-Asp) is believed to result from its unique mechanism of depleting the circulating pool of asparagine and glutamine.1 Asparagine depletion itself results in a selective starvation of lymphoid blast cells, which depend on serum asparagine as the source for protein synthesis and are unable to synthesize adequate amounts of asparagine de novo.2, 3 On the other side, interference of L-Asp with protein synthesis also results in several undesired effects, with imbalances in the coagulation system being one of the most common effects.4, 5 For cases with severe chemical coagulation abnormalities or particularly when bleeding episodes or thrombotic events have occurred, replacement therapy with fresh frozen plasma (FFP) is an accepted therapeutic option, although not generally recommended. With respect to the specific mode of action of L-Asp, we were interested in the question whether FFP may itself contain free asparagine, and whether FFP administration may, by that way, antagonize the therapeutic effect of L-Asp to some degree by repleting the circulating asparagine pool.

In order to further elucidate this issue, we performed an easy and reproducible assay, whose theoretical approach is explained by the biochemical pathway of L-Asp. The detailed metabolic action of L-Asp is determined by an enzymatic hydrolysis of the nonessential amino acids asparagine and glutamine to aspartic acid and glutamic acid, with generation of ammonia as a direct metabolite of this reaction. In a recent study, a reproducible and significant short-time elevation in plasma levels of ammonia was observed after L-Asp application, suggesting a direct correlation between the degree of increase in ammonia level and L-Asp enzyme activity.6 From the biochemical point of view, elevation of ammonia levels after L-Asp application can thus be interpreted as an indirect evidence of enzymatic cleavage of asparagine and glutamine.

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  1. Department of Paediatric Hematology and Oncology, St Anna Children's Hospital, Vienna, Austria. E-mail: georg.mann@stanna.at,

    M Steiner, A Attarbaschi, O A Haas, U Kastner, H Gadner & G Mann

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  1. M Steiner
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  2. A Attarbaschi
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  3. O A Haas
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  4. U Kastner
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  5. H Gadner
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  6. G Mann
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Steiner, M., Attarbaschi, A., Haas, O. et al. Fresh frozen plasma contains free asparagine and may replace the plasma asparagine pool during L-asparaginase therapy. Leukemia 22, 1290 (2008). https://doi.org/10.1038/sj.leu.2405051

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