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Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay
Published on: September 9, 2012
C-reactive protein-induced activated partial thromboplastin time prolongation in heparinized samples is attenuated by
Vadim Kostousov1, Sridevi Devaraj1, Karen Bruzdoski1
1Departments of Pathology & Immunology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, USA.
Insights
Elevated C-reactive protein (CRP) prolongs activated partial thromboplastin time (aPTT) in vitro, but this effect is not seen in pediatric ECMO patients due to increased factor VIII. The anti-Xa assay is preferred for heparin monitoring in these patients.
Area of Science:
- Pediatric critical care medicine
- Clinical pathology and laboratory diagnostics
- Hematology and thrombosis
Background:
- Activated partial thromboplastin time (aPTT) and anti-factor Xa (anti-Xa) activity are crucial for monitoring unfractionated heparin therapy in pediatric patients undergoing extracorporeal membrane oxygenation (ECMO).
- Elevated C-reactive protein (CRP) is known to interfere with aPTT, potentially causing discrepancies with anti-Xa assays.
Purpose of the Study:
- To investigate the impact of elevated CRP on aPTT and anti-Xa assays in the context of heparin administration.
- To determine if elevated CRP influences laboratory heparin monitoring in pediatric ECMO patients.
Main Methods:
- In vitro analysis of citrated normal specimens spiked with CRP, heparin, and factor VIII (FVIII), followed by measurement of aPTT and anti-Xa activity.
- Analysis of aPTT, anti-Xa activity, FVIII, fibrinogen, and CRP in 18 pediatric ECMO patient specimens.
- In vitro experiments to assess the effect of FVIII on CRP-induced aPTT prolongation in heparinized samples.
Main Results:
- In vitro, elevated CRP prolonged aPTT in both heparinized and non-heparinized normal specimens, but did not affect anti-Xa activity.
- ECMO specimens exhibited similar aPTT and anti-Xa values irrespective of CRP levels.
- Elevated CRP in ECMO samples correlated with increased fibrinogen and FVIII activity; co-administration of FVIII attenuated CRP-induced aPTT prolongation in vitro.
Conclusions:
- The in vitro prolongation of aPTT by CRP is mitigated in pediatric ECMO samples due to a concurrent increase in FVIII.
- Discrepancies between CRP and FVIII levels may explain aPTT/anti-Xa assay variability during heparin therapy in pediatric patients.
- The anti-Xa assay is recommended as the preferred method for heparin monitoring in pediatric ECMO settings.
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.
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