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Licensed Unlicensed Requires Authentication Published by De Gruyter August 5, 2019

Heparin and citrate additive carryover during blood collection

Martin H. Keppel, Simon Auer, Giuseppe Lippi, Alexander von Meyer, Michael Cornes, Thomas K. Felder, Hannes Oberkofler, Cornelia Mrazek, Elisabeth Haschke-Becher and Janne Cadamuro ORCID logo



Published evidence on the risk of additive carryover during phlebotomy remains elusive. We aimed to assess potential carryover of citrated and heparinized blood and the relative volume needed to bias clinical chemistry and coagulation tests.


We simulated standardized phlebotomies to quantify the risk of carryover of citrate and heparin additives in distilled water, using sodium and lithium as surrogates. We also investigated the effects of contamination of heparinized blood samples with increasing volumes of citrated blood and pure citrate on measurements of sodium, potassium, chloride, magnesium, total and ionized calcium and phosphate. Likewise, we studied the effects of contamination of citrated blood samples with increasing volumes of heparinized blood on heparin (anti-Xa) activity, lithium, activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). We interpreted these results based on measurement deviations beyond analytical, biological and clinical significance.


Standardized phlebotomy simulations revealed no significant differences in concentration of surrogate markers. Clinically significant alterations were observed after contamination of heparinized blood samples with volumes of citrated blood beyond 5–50 μL for ionized calcium and beyond 100–1000 μL for sodium, chloride and total calcium. Investigations of pure citrate carryover revealed similar results at somewhat lower volumes. Heparinized blood carryover showed clinically significant interference of coagulation testing at volumes beyond 5–100 μL.


Our results suggest that during a standardized phlebotomy, heparin or citrate contamination is highly unlikely. However, smaller volumes are sufficient to severely alter test results when deviating from phlebotomy guidelines.

Corresponding author: Janne Cadamuro, MD, University Hospital Salzburg, Paracelsus Medical University, Department of Laboratory Medicine, Salzburger Landeskliniken, Müllner Hauptstr. 48, 5020 Salzburg, Austria, Phone: 0043-57255-57263, Fax: 0043-57255-23199

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

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. 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: 2019-04-24
Accepted: 2019-07-11
Published Online: 2019-08-05
Published in Print: 2019-11-26

© 2019 Walter de Gruyter GmbH, Berlin/Boston

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