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Presentation Details
Comprehensive Coagulation Profiles and Fibrinolysis assessment at the point-of-care for Postpartum Hemorrhage Monitoring

Daniel Hoare1, Michaela Farber2, Seemantini Nadkarni1.

1Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.2Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

Abstract


Background Postpartum haemorrhage(PPH) is a leading cause of maternal mortality, accounting for up to 8% of maternal deaths in high resource settings and approximately 20% in low resource environments. Coagulopathy in the context of PPH significantly increases the risk of life-threatening bleeding. However, with timely and comprehensive profiling to diagnose and predict coagulopathic bleeding early, can combat PPH. Conventional coagulation testing(CCT) is often ineffective due to high costs of diagnostic tests, prolonged turnaround times and lack of access to haematology services. The iCoagLab is a recent point-of-care, portable coagulation monitoring platform that achieves comprehensive assessment of complete coagulation and fibrinolysis profiles in <10mins from just a few drops(25µL) of whole blood(Fig1A). Thus, by delivering multiple coagulation and fibrinolysis metrics within minutes using a small blood volume with inexpensive disposables at the point-of-care, the iCoagLab platform is poised to address the global challenge for preventing maternal deaths due to PPH in low resource settings.   Methodology iCoagLab measures the viscoelastic modulus through a non-contact methodology where a laser diode illuminates the blood sample and a low-cost CMOS camera acquires time varying speckle fluctuations, Fig1A. By tracking the movements of blood cells from speckle intensity fluctuations the viscoelastic modulus of the clotting sample is derived to measure several coagulation and fibrinolysis metrics in <10mins. Using a single integrated iCoagLab platform, four assays are tested. The intrinsic coagulation assay uses activated kaolin(AK) to measure thrombin generation time(iCoagLabR-Time), activated clotting time(iCoagLabACT), clot polymerization rate(iCoagLabAngle), and clot stiffness(iCoagLabMA)(Fig1B). The extrinsic coagulation assay determines prothrombin time throughiCoagLabPT. (Fig1C), and the fibrinogen assay uses a platelet inhibitor to isolate fibrin contribution to the clot to quantify fibrinogen via the iCoagLabFib parameter(Fig1D). To assess fibrinolysis, high concentration modified AK reagent was used to measure iCoagLabLysis Fig1E. For each assay precision testing was performed to acquire coefficient of Variation(COV) using multiple repeats of a sample. Assay were then compared to CCT values or known concentrations of tissue plasminogen activator(tPA) for fibrinolysis measurements. A pilot study investigating PPH patients admitted to the MGH labour and delivery department was performed by comparing this cohort to CCTs and TEG6s. Results All assays reported high precisions across all coagulation metrics with COV ranging from 5%-12.5%,(Fig1B-D). Furthermore, all iCoagLab parameters showed strong, statistically significant correlations when compared against CCT values(Fig, 2):iCoagLabACT vs activated partial thrombin time(aPTT)(r=0.73, p<0.0001, N=38);iCoagLabPT vs prothrombin time(r=0.86, p<0.0001, N=25); iCoagLabFib vs plasma fibrinogen(r=0.74, p<0.0001, N=25). Comparing the iCoagLabLysis to known tPA concentrations in spiked blood samples showed a significant inverse correlation,(r=-0.92, p<0.0001, N=14). Ongoing studies conducted from blood samples obtained from patients admitted to the MGH labor unit confirm the utility and applicability of the iCoagLab platform. Conclusions Our results confirm that the iCoagLab platform provides comprehensive coagulation and fibrinolytic assessment within minutes using just a few drops of blood and deliver multiplexed metrics that closely mirror CCT results. Thus, the capability to obtain rapid, and accurate results at the point-of-care using a low-cost instrument and inexpensive disposable, positions iCoagLab as a promising tool to manage PPH.

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