178. REAL TIME MEASUREMENT OF BLOOD COAGULATION TIME USING A FDA-APPROVED DYE
Name: Junxin Wang
Grad Year: 2019
Heparin anticoagulation therapy is a cornerstone of surgical and cardiovascular medicine. Despite this widespread use, the optimal dose of heparin is very difficult to achieve because its molecular weight (3-30 kDa), activity (25-50%), biodistribution, pharmacokinetics, and patient condition (gender, age, weight, tobacco use) vary widely. The active partial thromboplastin time (aPTT) monitors heparin in clinics, but suffers from long turnaround times, a variable reference range, limited utility with low molecular weight heparin (LMWH), and poor correlation to outcome. The narrow therapeutic window and limited detection of heparin make it become the second most common ICU medication error. Here, we demonstrate a real time, noninvasive assay to measure concentration of heparin in whole blood both in vitro and in vivo using photoacoustic imaging. The photoacoustic signal is well correlated with results from aPTT. There was also a strong correlation between heparin concentration and signal (R2>0.90) with stability for at least 15 minutes. The lowest concentration that could be detected was 0.3 U/mL heparin in PBS and 2.7 U/mL in human blood. We also noticed a peak near 710 nm that is unique to the heparin/methylene blue complex and is not seen in MB only. In animals treated with 200 U/mL heparin, we noted a 2.8-fold photoacoustic signal increase in blood relative to animals treated with MB and PBS (P<0.0001) and again noticed spectral behavior that could potentially be used to discriminate this signal over background optical absorption. We also confirmed that this approach is compatible with LMWH in PBS with a detection limit of 30 ug/ml. The photoacoustic signals were able to turned off by protamine which is the antidote of heparin.
Industry Application Area(s)
Life Sciences/Medical Devices & Instruments