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The influence of excipients commonly used in freeze drying on whole blood coagulation dynamics assessed by rotational thromboelastometry

  • Matthias Erber EMAIL logo and Geoffrey Lee
Published/Copyright: February 11, 2015
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 53 Issue 10

Abstract

Background: Lyophilized reagents are used on a daily basis in coagulation diagnostics. They often contain a number of excipients in addition to the active compound. Some of these excipients may, however, influence coagulation dynamics.

Methods: Besides from plasmatic coagulation bulking agents may influence platelet properties. We therefore studied the influence of a variety of bulking agents (glycine, mannitol, sucrose and trehalose) as well as a surfactant (Tween® 80) on whole blood coagulation using thromboelastometry (ROTEM®) and platelet function analysis (ROTEM® platelet).

Results: Both disaccharides as well as Tween® 80 did not influence whole blood coagulation in the concentration range investigated. The addition of glycine and mannitol solutions to the ROTEM® measurement leads to an impaired clot formation as well as overall clot strength while clotting initiation remained barely influenced. Hypertonic glycine and mannitol solutions exhibit different clot formation impairment when correlated to their osmolar concentration and compared to equally osmolar NaCl-solutions. The effect of glycine was assigned to fibrin formation impairment identified with the FIBTEM assay. Platelet function analysis revealed that hypertonic glycine solutions do not alter platelet function but hypertonic mannitol and NaCl solutions do.

Conclusions: While the influence observed for glycine may be due to fibrinogen precipitation, the mechanism of mannitol appears to be more complex as platelet function as well as fibrin-based clot formation are influenced. This study therefore demonstrates the necessity to check for coagulation impairment due to compounds contained in lyophilized reagents.

Keywords: glycine; hypertonic solutions; lyophilization; mannitol; thromboelastometry
Corresponding author: Matthias Erber, Division of Pharmaceutics, Friedrich-Alexander University Erlangen-Nürnberg, Cauerstrasse 4, 91058 Erlangen, Germany, E-mail:

Acknowledgments

The university medical center’s blood donation service as well as the volunteers are gratefully acknowledged for the preparation of the whole blood samples and their participation, respectively. Gaby Lange and Ilona Muslaeva are gratefully acknowledged for performing the ROTEM® platelet analysis and their expert technical assistance.

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Financial support: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2014-10-24
Accepted: 2015-1-5
Published Online: 2015-2-11
Published in Print: 2015-9-1

©2015 by De Gruyter

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https://doi.org/10.1515/cclm-2014-1046
Keywords for this article
glycine; hypertonic solutions; lyophilization; mannitol; thromboelastometry

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. New endocrine biomarkers and cardiovascular disease: is it time for routinely screening?
  4. Reviews
  5. Quantitative detection of amyloid-β peptides by mass spectrometry: state of the art and clinical applications
  6. Recent advances in biomarkers for Parkinson’s disease focusing on biochemicals, omics and neuroimaging
  7. Mini Review
  8. Serum calcitonin negative medullary thyroid carcinoma: a systematic review of the literature
  9. Genetics and Molecular Diagnostics
  10. ABCB1 (MDR-1) pharmacogenetics of tacrolimus in renal transplanted patients: a Next Generation Sequencing approach
  11. Novel association of FCGR2A polymorphism with age-related macular degeneration (AMD) and development of a novel CFH real-time genotyping method
  12. General Clinical Chemistry and Laboratory Medicine
  13. Assessing quality on the Sigma scale from proficiency testing and external quality assessment surveys
  14. Combining antibody tests and taking into account antibody levels improves serologic diagnosis of celiac disease
  15. Application of a point of care creatinine device for trend monitoring in kidney transplant patients: fit for purpose?
  16. LC-MS/MS method for hepcidin-25 measurement in human and mouse serum: clinical and research implications in iron disorders
  17. The relationship of fibroblast growth factors 21 and 23 and α-Klotho with platelet activity measured by platelet volume indices
  18. Neurofilament medium polypeptide (NFM) protein concentration is increased in CSF and serum samples from patients with brain injury
  19. Methods to identify saline-contaminated electrolyte profiles
  20. An international study of how laboratories handle and evaluate patient samples after detecting an unexpected APTT prolongation
  21. The influence of excipients commonly used in freeze drying on whole blood coagulation dynamics assessed by rotational thromboelastometry
  22. Reference Values and Biological Variations
  23. Biological variation of plasma osmolality obtained with capillary versus venous blood
  24. Mining of hospital laboratory information systems: a model study defining age- and gender-specific reference intervals and trajectories for plasma creatinine in a pediatric population
  25. Cancer Diagnostics
  26. Fascin is a circulating tumor marker for head and neck cancer as determined by a proteomic analysis of interstitial fluid from the tumor microenvironment
  27. Diabetes
  28. First trimester concentrations of the TTR-RBP4-retinol complex components as early markers of insulin-treated gestational diabetes mellitus
  29. Corrigendum
  30. Corrigendum to: Performance criteria and quality indicators for the pre-analytical phase
  31. Letters to the Editors
  32. Pediatric reference intervals for calculated free testosterone, bioavailable testosterone and free androgen index in the CALIPER cohort
  33. Two novel genomic rearrangements identified in suicide subjects using a-CGH array
  34. Association between physical fitness and mean platelet volume in professional soccer players
  35. Laboratory biomarkers and frailty: presentation of the FRAILOMIC initiative
  36. Spuriously high platelet counts by various automated hematology analyzers in a patient with disseminated intravascular coagulation
  37. To avoid fasting time, more risk than benefits
  38. Daily communication decreases the number of pre-analytical errors in primary care
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  41. FTL gene mutation and persistent hyperferritinemia without iron deficiency anemia after phlebotomy
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