C-reactive protein-induced activated partial thromboplastin time prolongation in heparinized samples is attenuated by elevated factor VIII

Vadim Kostousov, Sridevi Devaraj, Karen Bruzdoski, Lisa Hensch, Shiu Ki Hui, Jun Teruya

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Introduction: Activated partial thromboplastin time (aPTT) and antifactor Xa (anti-Xa) activity are used to monitor unfractionated heparin therapy in children on extracorporeal membrane oxygenation (ECMO). Elevated C-reactive protein (CRP) can prolong aPTT and cause discrepancy between these two assays. We aimed to evaluate CRP effect on aPTT and anti-Xa assays in the presence of heparin and to determine whether elevated CRP affects laboratory monitoring in pediatric ECMO patients. Materials and methods: Citrated normal specimens were spiked with CRP, heparin, and recombinant factor VIII (FVIII) and followed by measurement of aPTT and anti-Xa activity. Additionally, aPTT, anti-Xa activity, FVIII, fibrinogen, and CRP were measured in 18 ECMO specimens. Results: Elevated CRP prolonged aPTT in normal specimens with or without heparin, but did not affect anti-Xa assay. In contrast, ECMO specimens showed similar aPTT and anti-Xa values regardless of CRP level. Elevated CRP in specimens was accompanied by increased fibrinogen and FVIII activity. Additional in vitro experiments confirmed that FVIII spiked simultaneously with CRP attenuated CRP-induced aPTT prolongation in heparinized specimens. Conclusion: In vitro CRP-induced aPTT prolongation is not observed in pediatric ECMO samples due to concomitant FVIII increase. Discordant changes of CRP and FVIII in plasma could contribute to aPTT/anti-Xa discrepancies observed during heparin therapy in the pediatric population. The anti-Xa assay is preferable for heparin monitoring in pediatric ECMO settings.

Original languageEnglish (US)
Pages (from-to)139-142
Number of pages4
JournalInternational Journal of Laboratory Hematology
Volume43
Issue number1
DOIs
StatePublished - Feb 2021

Keywords

  • activated partial thromboplastin time
  • antifactor Xa
  • C-reactive protein
  • extracorporeal membrane oxygenation
  • factor VIII

ASJC Scopus subject areas

  • Hematology
  • Clinical Biochemistry
  • Biochemistry, medical

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