Elevated activated partial thromboplastin time-based clot waveform analysis markers have strong positive association with acute venous thromboembolism

Abstract

Introduction: A hypercoagulable state is a predisposition for venous thromboembolism (VTE). The activated partial thromboplastin time (aPTT)-based clot waveform analysis (CWA) is a global haemostatic measure but its role in assessment of hypercoagulability and thrombotic disorders is uncertain. We aimed to study the changes of CWA parameters in acute VTE. We hypothesized that patients with acute VTE would demonstrate higher CWA values than control patients without VTE and having elevated CWA parameters is associated with acute VTE.

Materials and methods: Clot waveform analysis data from patients (N = 45) with objectively proven acute VTE who had an aPTT performed prior to initiation of anticoagulation were compared with controls (N = 111). The CWA parameters measured were min1, min2, max2 and delta change.

Results: While the mean aPTT between VTE patients and controls did not differ (P = 0.830), the mean CWA parameters were significantly higher among VTE patients than controls (min1, P < 0.001; min2, P = 0.001; max2, P = 0.002; delta change, P < 0.001). There were significantly more cases within the VTE group exhibiting CWA values above their reference intervals than the control group (all P < 0.001), with the odds ratios for VTE of 8.0, 5.2, 4.8 and 18.6 for min1, min2, max2 and delta change, respectively (all P < 0.001).

Conclusions: Patients with acute VTE had elevated aPTT-based CWA parameters than controls. Higher CWA parameters were significantly associated with acute VTE.

Keywords: activated partial thromboplastin time; blood coagulation; thrombophilia; thrombosis; venous thromboembolism.

Figure 1

A representative clot waveform curve, its analysis and parameters. (a) The original transmittance curve obtained from the routine aPTT test. (b) The first derivative curve derived from the original transmittance curve. (c) The second derivative curve derived from the first derivative curve.

Figure 2

Receiver operating characteristics (ROC) curves and area under the curve (AUC) of the various CWA parameters (min1, min2, max2 and delta change individually as well as the composite of all these four markers) derived from logistic regression models using the upper limit of the reference interval of each CWA parameter. CWA - clot waveform analysis.