Presentation Details
| Investigating the Relationship between D Dimer levels and Viscoelastic Characteristics of Blood Clots Eli J Foster, Nathaniel Hai, Seemantini K Nadkarni. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA |
Abstract
Background Thrombotic activity is often monitored through the measurement of D Dimer concentration in blood plasma, with elevated levels of D Dimer leading to an escalation in care and monitoring for venous thromboembolism (VTE). The D Dimer test has high sensitivity, but low specificity as an indicator for VTE, frequently leading to unnecessary escalations in care [1]. Here, we investigate the relationship between D Dimer concentration and the viscoelastic properties of blood clots derived from measurements of laser speckle fluctuations in whole blood. Objectives We aim to investigate the relationship between D Dimer levels and viscoelastic properties of whole blood clots in order to develop a more specific and actionable metric for VTE risk. Methods The viscoelastic properties of whole blood clots are measured using iCoagLab, a point-of-care instrument that analyzes time-varying speckle intensity fluctuations to quantify blood coagulation status. Laser speckle intensity fluctuations arise from endogenous thermal motion of scattering particles, such as blood cells in the illuminated blood sample. During coagulation, the formation of a fibrin clot restricts the motion of blood cells, which slows down the rate of temporal speckle intensity fluctuations monitored by iCoagLab. For this study, we collected excess blood samples from 45 patients from the hematology core lab at Massachusetts General Hospital. D Dimer levels were measured using a standard latex agglutination assay, where concentrations greater than 500 ng/mL fibrin equivalent units were considered test-positive. We initiated the intrinsic coagulation pathway using a 6.89 mg/mL concentration of activated kaolin and used iCoagLab to measure the viscoelastic modulus of the blood until it reached a plateau phase, as shown in figure 1. From this coagulation curve, we extract intrinsic coagulation parameters related to the rate (reaction time, R; activated clotting time, ACT; and clot rate, angle) and mechanical strength (maximum amplitude, MA) of clot formation. iCoagLab parameters were compared with core lab plasma fibrinogen and D dimer levels using linear regression analysis. We included an analysis of fibrinogen because it is significantly involved in the initiation of clot formation and, therefore, may be useful in the analysis of D Dimer as a product of fibrinolysis. Results We observe a statistically significant negative correlation between iCoagLab MA and both fibrinogen (r=0.60, p<0.001) and D Dimer concentration (r=-0.32, p<0.05) (figure 2). The D Dimer correlation is noticeably stronger when only considering samples with a D Dimer value greater than 2000 ng/mL (r=-0.49, p<0.001). There is much more deviation from the overall trend for samples with D Dimer values less than 2000 ng/mL, though these results still warrant escalations in care. No correlation was observed for other iCoagLab parameters. Conclusions and Next Steps We report statistically significant relationships between D Dimer concentration and the maximum viscoelastic amplitude of intrinsically activated blood clots, as measured by iCoagLab. The relationship weakens for samples with D Dimer values below 2000 ng/mL. Further studies will be necessary to evaluate whether iCoagLab may offer higher specificity compared to D Dimer levels to predict VTE outcomes in patients in the future.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.