Lipoprotein-complexed C-reactive protein and the biphasic transmittance waveform in critically ill patients

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.