The value of the activated partial thromboplastin time (APTT) has been well described by the Forum authors in relation to its clot–endpoint determination [1–6]. Its performance also has added value and enabled our group to unravel the existence of a calcium-dependent complex between C-reactive protein (CRP) and very low-density lipoprotein (VLDL) [7]. Although Rowe et al. [8] have shown that this complex can be induced by incubating acute-phase serum containing elevated CRP levels with serum from type III hyperlipidemic patients, our investigations have clearly demonstrated its existence in vivo in critically ill patients [7]. In addition, we have also provided pathophysiological insight into the role of this complex which might outwardly be more relevant to cardiovascular disease, but is actually pertinent to critical care biology. All this stemmed from initial serendipitous observations of an atypical, biphasic light transmittance profile of clot formation in the performance of the APTT on samples from patients with disseminated intravascular coagulation (DIC) [9]. Further work by ourselves and others have shown that its detection has prognostic significance and can be useful in the monitoring of critically ill patients [10–12]. The close correlation between changes in the biphasic waveform and clinical events led us to hypothesize that there was an underlying biological mechanism and to this end, the great skills of Mike Nesheim enabled us to unravel its molecular composition and further demonstrate that the extent of CRP–VLDL complex formation correlated with the degree of the biphasic waveform abnormality. Although it is still early days in understanding the full pathophysiological consequence of this complex, it appears to link to DIC in that the VLDL component can enhance thrombin generation and procoagulant activity by at least 2.5-fold [13]. Indeed, a shortened APTT clot-time is often noted with the biphasic waveform. This highlights the relevance of performing the APTT beyond the traditional significance of clot-time prolongation to the pathophysiological significance of faster endpoint determinations. Shorter APTT clot-times have been demonstrated to predict adverse outcome in terms of general mortality in a general hospital setting [14] and more recently, associated with venous thromboembolic risk [15]. As with its importance in the development of the activated protein C resistance assay [5], the APTT promises to evolve beyond its well-archived role [16] to present a further, fresh dimension to the coagulationist in a new era of diagnostic importance, mechanistic understanding and research development.


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