Biphasic Waveform of the Activated Partial Thromboplastin Time (A2 Flag) Is Associated with Adverse Events in the Coronary Care Unit.

Objective: An abnormality of the optical transmission waveform obtained during measurement of the activated partial thromboplastin time (aPTT) has been described in association with DIC and sepsis. This biphasic waveform (BWF) is caused by the in vitro formation of Ca²⁺-induced complexes between VLDL and CRP. A review of the literature revealed no studies on the BWF in cardiac patients. The purpose of this study was to determine whether the BWF is associated with adverse clinical outcomes among patients in a Coronary Care Unit (CCU).

Patients: Consecutive patients admitted to the CCU over a two-month period (n=83) were retrospectively evaluated. Standard of clinical care was not altered.

Methods: Laboratory results including aPTT, aPTT waveform analysis, troponin, beta-natriuretic peptide (BNP), complete blood count (CBC), basic metabolic panel (BMP), and high sensitivity C-reactive protein (hsCRP) were analyzed when available. BWF values beyond a pre-set threshold [5 SD’s lower than the mean value of a normal population (n=40)] were signaled by the A2 Flag. Hospital charts were reviewed to determine coronary artery disease (CAD), hypertension (HTN), diabetes mellitus (DM), hyperlipidemia, and renal dysfunction. Hospital course including invasive and surgical procedures and medical interventions were recorded.

Results: The A2 Flag was detected in 23 of 83 patients (27.7%) during the entire course of CCU treatment. Using a lower Slope_1 threshold value (as had been used in the DIC/sepsis studies) produced an A2 flag in >90% of the patients. Patients in the A2 Flag and no-Flag groups were comparable for age, gender, HTN, DM and hyperlipidemia. Of the patients with an A2 Flag, 73.9% had acute coronary syndrome (encompassing the spectrum of clinical conditions ranging from unstable angina to non-ST-segment elevation MI to ST-segment elevation MI) vs 59.6% in the no-Flag group, 95.6% had CAD vs 83.8%, 52.1% had arrhythmia vs 32.2% (p=0.020), 60.8% had renal dysfunction (creatinine >1.5) vs 32.2% (p=0.002), 47.8% had elevated BNP vs 22.5% (p=0.037), and 73.9% had elevated troponin vs 50.0%. Length of stay was longer in the A2 Flag group (16.2 vs 7.2 days; p<0.001). Six of seven patients that expired had an A2 Flag. One patient with an A2 Flag expired during a subsequent readmission shortly after the course of this study.

Conclusion: The A2 Flag result is reported with the aPTT and thus is a rapid test available at no additional cost. As an adjunct to routine lab testing, aPTT waveform analysis appears to be a novel means to identify a select population of CCU patients that are at higher risk for adverse cardiac events and warrants further investigation. This pilot study is being used to develop a larger prospective study to determine if the A2 Flag can improve patient care through earlier diagnosis and treatment intervention.