Early Identification and Prognostic Implications in Disseminated Intravascular Coagulation through Transmittance Waveform Analysis

Abstract

SummaryEfforts to improve the prognosis in disseminated intravascular coagulation (DIC) have been hampered by the lack of an early, useful and rapidly available diagnostic marker. More recently, a characteristic bi-phasic change in the light transmittance waveform profile of the APTT assay has been associated with DIC. In this prospective study, we have assessed the utility of this assay in the routine clinical setting. 1,470 samples were analysed from 747 patients and 41 patients had DIC. The sensitivity and specificity of the bi-phasic waveform pattern for DIC was 97.6% and 98% respectively. The appearance of a biphasic waveform preceded the development of abnormalities in the standard laboratory tests for DIC and waveform changes correlated closely with clinical events. In conclusion, transmittance waveform analysis is not only useful as an early diagnostic and single monitoring marker of DIC but the quantifiable and standardisable changes also allow for prognostic applicability in clinical management.

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

“…The methodology has been described in detail elsewhere. [1][2][3][4] In brief, the MDA 180 uses a variable wavelength photo-optical detection system and can chart and quantify changes in light transmission when the plasma clots after activation and recalcification. Normal and biphasic waveforms at 580 nm are illustrated in Figure 1.…”

“…1,2 The biphasic waveform (BPW) was initially described when a decrease in plasma light transmittance before clot formation on the MDA 180 automated coagulation analyzer was shown to correlate with disseminated intravascular coagulation (DIC) in critically ill patients. [3][4][5] In contrast to the normal sigmoidal waveform pattern that is characterized by an initial 100% light transmittance phase before clot formation, patients with a biphasic pattern had an immediate, progressive decrease in light transmittance that occurred even in the preclotting phase. The magnitude of this BPW often varied with sequential samples taken from individual patients and appeared early in samples from patients who were later diagnosed with DIC by more conventional criteria.…”

“…A subsequent prospective study, 4 in which all samples received in a diagnostic laboratory over a 2-week period were examined, indicated that the sensitivity and specificity of the BPW for DIC are 97.6% and 98%, respectively. An overall positive predictive value of 74% was obtained, and this value increased with increasing falls in light transmittance.…”

Specificity of commonly used cyclic nucleotides with PKA, PKG and Epac-implementing microcalorimetry to determine PDE activities

“…The study is extended to eight cyclic nucleotide hydrolysing phosphodiesterases (PDE IA, IB, IC, II, IV, V, VI and X), thereby introducing microcalorimetry to overcome radioactive labeling of the tested analogs and allowing analysis of the kinetic parameters K m , K i and V max [1].…”

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

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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.

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