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Upregulation of the antithrombotic protein C pathway at birth
J Petäjä1, J A Fernández, V Fellman
1Department of Molecular, Scripps Research Institute, La Jolla, California, USA. jari.petaja@dec.fi
Insights
Healthy newborns have a well-developed protein C pathway, crucial for preventing blood clots. Despite lower protein C levels, their blood shows enhanced anticoagulation activity at birth.
Area of Science:
- Biochemistry
- Neonatal Physiology
- Hemostasis
Background:
- Serious thrombotic complications are observed in sick neonates, contrasting with the low thrombosis risk in healthy infants.
- Understanding physiological anticoagulation regulation at birth is critical for neonatal health.
- The protein C pathway plays a vital role in regulating blood coagulation and preventing thrombosis.
Purpose of the Study:
- To investigate the functional status of the protein C pathway in healthy term newborns at birth.
- To compare the protein C pathway components and activity between neonatal cord plasma and adult plasma.
- To elucidate the mechanisms contributing to anticoagulation in the neonatal period.
Main Methods:
- Measurement of zymogen protein C and activated protein C (APC) levels in cord plasma from 14 healthy newborns and 10 adult controls.
- Assessment of APC inactivation rates and APC sensitivity ratio using activated partial thromboplastin time (aPTT) assays.
- Comparative analysis of protein C pathway components and functional activity between neonatal and adult plasma samples.
Main Results:
- Zymogen protein C levels were significantly lower in cord plasma compared to adult plasma (37% vs. 90%).
- Activated protein C (APC) levels were not significantly different, but relative to protein C, cord plasma had a 5.2-fold higher APC level.
- APC inactivation was slower in cord plasma (half-life 50 min vs. 27 min), and APC demonstrated increased sensitivity in inactivating factor V in neonatal plasma.
Conclusions:
- Despite reduced zymogen protein C, the protein C pathway in healthy newborns appears functionally robust and activated at birth.
- The enhanced anticoagulation in neonates is supported by slower APC inactivation and increased APC-mediated factor V inactivation.
- These findings suggest a well-developed physiological anticoagulation system in newborns, contributing to their low risk of thrombosis.
Abstract:
Serious thrombotic complications occur in sick neonates, while healthy infants have a very low risk of thrombosis. To better understand the regulation of physiological anticoagulation at birth, components of the protein C pathway were measured in cord plasma samples from 14 full-term healthy newborns and in samples from 10 adult controls. Although zymogen protein C was significantly reduced in cord plasma (mean +/- SEM in cord vs. adult sample 37 +/- 1.4% vs. 90 +/- 5.5%, p < 0.0001), levels of the active enzyme, activated protein C (APC), were not (119 +/- 20% vs. 75 +/- 12%, p = 0.0762). Relative to the protein C level, cord plasmas had a 5.2-fold higher APC level (p < 0.01). The APC increase was partially due to slower inactivation of APC in cord plasma (half-life for APC 50 min in cord plasma vs. 27 minutes in adult plasma). Increased sensitivity of factor V to inactivation by APC in cord plasma was observed since the activated partial thromboplastin time-based APC sensitivity ratio was significantly increased for cord vs. adult plasma samples (2.28 +/- 0.09 versus 1.97 +/- 0.03, p < 0.01). Thus, despite low zymogen protein C, the protein C pathway in newborns seems to be functionally well developed and at an activated stage at birth.