Prothrombinase enhancement through quantitative and qualitative changes affecting very low density lipoprotein in complex with C-reactive protein

Michael W. Dennis; Colin Downey; Nicole Brufatto; Michael E. Nesheim; Ken Stevenson; Cheng Hock Toh

doi:10.1160/TH03-08-0548

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 91(03): 522-530
DOI: 10.1160/TH03-08-0548

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Prothrombinase enhancement through quantitative and qualitative changes affecting very low density lipoprotein in complex with C-reactive protein

Michael W. Dennis

¹ Roald Dahl Haemostasis and Thrombosis Centre, Royal Liverpool University Hospital, UK

,

Colin Downey

¹ Roald Dahl Haemostasis and Thrombosis Centre, Royal Liverpool University Hospital, UK

,

Nicole Brufatto

² Department of Biochemistry, Queen’s University, Canada

,

Michael E. Nesheim

² Department of Biochemistry, Queen’s University, Canada

,

Ken Stevenson

³Thrombosis Reference Centre,Withington Hospital, UK

,

Cheng Hock Toh

¹ Roald Dahl Haemostasis and Thrombosis Centre, Royal Liverpool University Hospital, UK

› Author Affiliations

Abstract

Summary

The biphasic waveform that can predict for disseminated intravascular coagulation (DIC) is due to the formation of a calcium-dependent complex between C reactive protein (CRP) and very low density lipoprotein (VLDL). As thrombin generation is pivotal to DIC, this aspect has been specifically investigated and the VLDL component has been found to increase prothrombinase activity via both quantitative and qualitative changes. The specific prothrombinase activity of VLDL from patients manifesting the biphasic waveform was 2.5 times that of normal individuals or critically ill patients without the biphasic waveform. This activity was due to an increase in anionic phospholipid surfaces that could be inhibited with excess annexin V and which was dependent on structurally intact apolipoprotein B.The qualitative change appeared to be due to a deficiency of phosphatidylethanolamine inVLDL from patients with the biphasic waveform.The functional consequence of this enhanced prothrombinase activity was an increased procoagulant effect in plasma. Using a modified activated partial thromboplastin time assay, the mean normal clot time decreased significantly when VLDL from patients with biphasic waveforms was substituted.These results indicate that VLDL derived from patients with the biphasic waveform can enhance thrombin procoagulant activity. As the CRP-VLDL complex exists in vivo, it could have a pathogenic role in disseminating the process of intravascular coagulation.

Keywords

DIC - lipoproteins - phospholipids - thrombin - sepsis

Full Text

References

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