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This article is part of the supplement: 3rd International Conference on cGMP Generators, Effectors and Therapeutic Implications

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The formation of a Ca2+-dependent complex of C-reactive protein and very low density lipoprotein causes the biphasic transmittance waveform

Michael Nesheim1*, John Samis2, John Walker1, Timothy Fischer35, Liliana Tejidor3, Greg Jones3, Wim Houdijk3, Alan Giles3, Lev Becker1, Marlys Koschinsky1, Richard Wenstone4, Colin Downey4 and Cheng Hock Toh4

Author Affiliations

1 Department of Biochemistry, Queen's University, Kingston, Ontario, Canada, K7L 3N6

2 Department of Pathology, Queen's University, Kingston, Ontario, Canada, K7L 3N6

3 Organon Teknika Corporation, Durham, NC 27712, USA

4 Department of Haematology, Royal Liverpool University Hospital, Liverpool, L7 8XP, UK

5 Ventana Medical Systems, Tucson, Arizona, USA

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BMC Pharmacology 2007, 7(Suppl 1):P42  doi:10.1186/1471-2210-7-S1-P42

The electronic version of this article is the complete one and can be found online at:

Published:25 July 2007

© 2007 Nesheim et al; licensee BioMed Central Ltd.

Clinical background

The "biphasic transmittance waveform" (BTW) refers to a time-dependent decrease in light transmittance that often occurs prior to clotting when performing the activated partial thromboplastin time (aPTT) assay with plasmas of critically ill patients on the MDA® coagulation analyzer [1]. Early observations showed an association of the BTW with disseminated intravascular coagulation (DIC) and clinical outcome. (See Table 1) The magnitude of the BTW was assessed against in-patient mortality. A total of 346 patients were found to have a BTW on admission to the ITU with a mortality rate of 44%, as compared with 26% for those with normal waveforms. A stepwise increase in the likelihood of mortality was directly correlated with the degree of drop in light transmittance observed on admission (see Figure 1). The mortality fraction was 0.3 in those with normal waveforms versus 0.6 when the light transmittance decreased by 30%.

Table 1. CRP by indicators of social class in VERA.

thumbnailFigure 1. Immunoblot of monoclonal antibodies against IROMPs of A. baumannii ATCC 19606 Immunoblot of Monoclonal antibodies with OMP of A. baumannii grown in CDM-Fe medium. Molecular Weight markers were marked in kDa. Lane A. 2GgABIR; B. 3D5ABIR C. 1D11ABIR D. 5D6ABIR E. 1F7ABIR F. +ve control G. -ve control.


Detection and analysis of an atypical biphasic aPTT clot waveform is a strong and early predictor of clinical outcome in patients admitted to the ITU. The formation of lipoprotein-complexed C-reactive protein (LC-CRP) is the biochemical basis of the biphasic waveform seen in these patients.


  1. Downey C, Kazmi R, Toh CH: Early identification and prognostic implications in disseminated intravascular coagulation through transmittance waveform analysis.

    Thromb Haemost 1998, 80:65-69. PubMed Abstract | Publisher Full Text OpenURL