Prothrombinase enhancement through quantitative and qualitative changes affecting very low density lipoprotein in complex with C-reactive protein.
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 in VLDL 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.
Roald Dahl Haemostasis & Thrombosis Centre, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, United Kingdom.
Michael W
MW
Dennis
Colin
C
Downey
Nicole
N
Brufatto
Michael E
ME
Nesheim
Ken
K
Stevenson
Cheng Hock
CH
Toh
D000327:Adsorption; D017304:Annexin A5 / Q000494:pharmacology; D001055:Apolipoproteins B / Q000378:metabolism; D001780:Blood Coagulation Tests; D002097:C-Reactive Protein / Q000378:metabolism*; D002469:Cell Separation; D002554:Cerebrosides / Q000378:metabolism; D002855:Chromatography, Thin Layer; D003029:Coagulants / Q000378:metabolism; D004211:Disseminated Intravascular Coagulation; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007163:Immunosorbent Techniques; D008074:Lipoproteins / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D010314:Partial Thromboplastin Time; D010714:Phosphatidylethanolamines / Q000378:metabolism; D011485:Protein Binding; D018805:Sepsis; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D017304:Annexin A5; D001055:Apolipoproteins B; D002554:Cerebrosides; D003029:Coagulants; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D010714:Phosphatidylethanolamines; D014280:Triglycerides; C483858:phosphatidylethanolamine; D002097:C-Reactive Protein; D013925:Thromboplastin; D013917:Thrombin