title: Biphasic transmittance waveform in the APTT coagulation assay is due to the formation of a Ca(++)-dependent complex of C-reactive protein with very-low-density lipoprotein and is a novel marker of impending disseminated intravascular coagulation.
abstract: A decrease in light transmittance before clot formation, manifesting as a biphasic waveform (BPW) pattern in coagulation assays, was previously correlated with the onset of disseminated intravascular coagulation (DIC). In this study of 1187 consecutive admissions to the intensive care unit, the degree of this change on admission predicts DIC better than D-dimer measurements. Additionally, the BPW preceded the time of DIC diagnosis by 18 hours, on average, in 56% (203 of 362) of DIC patients. The BPW is due to the rapid formation of a precipitate and coincident turbidity change on recalcification of plasma. The isolated precipitate contains very-low-density lipoprotein (VLDL) and C-reactive protein (CRP). The addition of CRP and Ca(++) to normal plasma also causes the precipitation of VLDL and IDL, but not LDL or HDL. The K(d) of the CRP/VLDL interaction is 340 nM, and the IC(50) for Ca(++) is 5.0 mM. In 15 plasmas with the BPW, CRP was highly elevated (77-398 microg/mL), and the concentration of isolated VLDL ranged from 0.082 to 1.32 mM (cholesterol). The turbidity change on recalcification correlates well with the calculated level of the CRP-VLDL complex. Clinically, the BPW better predicts for DIC than either CRP or triglyceride alone. The complex may have pathophysiological implications because CRP can be detected in the VLDL fraction from sera of patients with the BPW, and the VLDL fraction has enhanced prothrombinase surface activity. The complex has been designated lipoprotein complexed C-reactive protein.
authors.affiliation: Departments of Biochemistry and Pathology, Queen's University, Kingston, ON, Canada.
authors.forename: Cheng Hock
authors.initials: CH
authors.lastname: Toh
authors.forename: John
authors.initials: J
authors.lastname: Samis
authors.forename: Colin
authors.initials: C
authors.lastname: Downey
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: 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: Larry O
authors.initials: LO
authors.lastname: Ticknor
authors.forename: Ray
authors.initials: R
authors.lastname: Paton
authors.forename: Richard
authors.initials: R
authors.lastname: Wenstone
authors.forename: Michael
authors.initials: M
authors.lastname: Nesheim
mesh_terms: D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000097:blood*; D009391:Nephelometry and Turbidimetry / Q000379:methods; D010314:Partial Thromboplastin Time; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D008079:Lipoproteins, VLDL; D011994:Recombinant Proteins; D002097:C-Reactive Protein; D002118:Calcium