title: Lipoprotein-complexed C-reactive protein and the biphasic transmittance waveform in critically ill patients.
abstract: The 'biphasic transmittance waveform' (BTW) refers to a decrease in light transmittance that often occurs prior to clotting in coagulation assays of critically ill patient plasmas. It correlates with disseminated intravascular coagulation and mortality. The present work shows that the BTW is due to the rapid formation of a precipitate and a coincident change in turbidity in re-calcified plasma. The precipitate was isolated from patient plasma and contained lipids typical of very low density lipoprotein (VLDL), plus the proteins apolipoprotein B-100 and C-reactive protein (CRP). Precipitation also occurred in normal plasma supplemented with CRP. In addition, CRP precipitated with VLDL and intermediate density lipoprotein, but not low density lipoprotein or high density lipoprotein. The Kd value for the CRP/VLDL interaction is 340 nM. The IC50 value of Ca2+ for complex formation is 5.0 mM, and epsilon-aminocaproic acid inhibits the process. In 15 plasmas with the BTW from critically ill patients, CRP was highly elevated (77-398 microg/mL) and VLDL cholesterol ranged from 0.082 to 1.32 mM. The magnitude of the turbidity change on re-calcification correlated well with the calculated level of the CRP/VLDL complex. Thus, the Ca2+-dependent formation of a complex between CRP and VLDL accounts for the BTW.
authors.affiliation: Department of Biochemistry, Queen's University, Kingston, Ontario, Canada. nesheimm@post.queensu.ca
authors.forename: Michael
authors.initials: M
authors.lastname: Nesheim
authors.forename: John
authors.initials: J
authors.lastname: Samis
authors.forename: John
authors.initials: J
authors.lastname: Walker
authors.forename: Lev
authors.initials: L
authors.lastname: Becker
authors.forename: Nicole
authors.initials: N
authors.lastname: Brufatto
authors.forename: Timothy
authors.initials: T
authors.lastname: Fischer
authors.forename: Liliana
authors.initials: L
authors.lastname: Tejidor
authors.forename: Greg
authors.initials: G
authors.lastname: Jones
authors.forename: Wim
authors.initials: W
authors.lastname: Houdijk
authors.forename: Alan
authors.initials: A
authors.lastname: Giles
authors.forename: Marlys
authors.initials: M
authors.lastname: Koschinsky
authors.forename: Richard
authors.initials: R
authors.lastname: Wenstone
authors.forename: Colin
authors.initials: C
authors.lastname: Downey
authors.forename: Cheng Hock
authors.initials: CH
authors.lastname: Toh
mesh_terms: D002097:C-Reactive Protein / Q000378:metabolism*; D002114:Calcinosis; D016638:Critical Illness; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008079:Lipoproteins, VLDL / Q000097:blood* / Q000145:classification; D009391:Nephelometry and Turbidimetry
chemical_list: D008079:Lipoproteins, VLDL; D002097:C-Reactive Protein