In this pilot study, microfluidic flow analysis and atomic force microscopy (AFM), are used, to determine microrheological properties of the blood – aggregation, and deformability of erythrocytes in women with preeclampsia (PE). The aggregation of red blood cells (RBCs) is evaluated with the microfluidic system BioFlux, by applying an experimental approach and image analysis created by the authors of this study. The elastic properties of erythrocytes are defined by Young’s modulus, using AFM. The aggregation index of erythrocytes and their elastic modulus are statistically significantly increased in patients with PE, in comparison to healthy normotensive pregnant women. In addition, it is found that the RBCs are less deformable and the interaction between them in aggregates is stronger in women with preeclampsia as compared with healthy pregnant women.
- Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Obstet Gynecol 122: 1122–1131, (2013).
- B. Csiszar, G. Galos, S. Funke, et al. Peripartum Investigation of Red Blood Cell Properties in Women Diagnosed with Early- Onset Preeclampsia. Cells, 10, 2714 (2021).
- J. D. Hernandez Hernandez, O. R. Villasenor, J. Del Rio Alvarado, et al. Morphological changes of red blood cells in peripheral blood smear of patients with pregnancy-related hypertensive disorders. Arch Med Res 46: 479–483. 17 (2015).
- F. G. Cunningham, T. Lowe, S. Guss, R. Mason. Erythrocyte morphology in women with severe preeclampsia and eclampsia. Preliminary observations with scanning electron microscopy. Am J Obstet Gynecol. 153(4):358-63 (1985).
- I. Giosheva, V. Strijkova, R. Komsa-Penkova, et al. Membrane Lesions and Reduced Life Span of Red Blood Cells in Preeclampsia as Evidenced by Atomic Force Microscopy. Int. J. Mol. Sci., 24, 7100 (2023).
- L. Heilmann, W. Rath, K. Pollow. Hemorheological changes in women with severe preeclampsia. Clin Hemorheol Microcirc 31: 49–58 (2004).
- G. D. Lang, G. D. Lowe, J. J. Walker, et al. Blood rheology in pre-eclampsia and intrauterine growth retardation: effects of blood pressure reduction with labetalol. Br J Obstet Gynaecol. 91(5):438-43 (1984).
- D. J. Pepple, M. R. Hardeman, A. M. Mullings, H. L. Reid. Erythrocyte deformability and erythrocyte aggregation in preeclampsia. Clin Hemorheol Microcirc. 24(1):43-8 (2001).
- C. Murali, P. Nithiarasu. Red blood cell (RBC) aggregation and its influence on non-Newtonian nature of blood in microvasculature. J of Modeling in Mechanics and Materials, 1 (1), 20160157 (2017).
- A. L. Tranquilli, G. G. Garzetti, G. De Tommaso, et al. Nifedipine treatment in preeclampsia reverts the increased erythrocyte aggregation to normal. Am J Obstet Gynecol. 167(4):942-5 (1992).
- G. F. von Tempelhoff, E. Velten, A. Yilmaz, et al. Blood rheology at term in normal pregnancy and in patients with adverse outcome events. Clin Hemorheol Microcirc. 42(2):127- 39 (2009).
- R. Csorba, A. Yilmaz, P. Tsikouras, et al. Rheological parameters in the umbilical cord blood in moderate and severe forms of preeclampsia. Clin Hemorheol Microcirc. 55(4):391- 401 (2013).
- P. Ozanne, F. C. Miller, H. J. Meiselman. RBC Aggregation in Diabetic and Pre-eclamptic Pregnancy. Clin Hemorheol Microcirc. 3(2):145 – 154 (1983).
- M. N. Karemore, J. G. Avari. Alteration in zeta potential of erythrocytes in preeclampsia patients. In: Prediction of maternal and fetal syndrome of preeclampsia (2019).
- B. Schauf, U. Lang, P. Stute, et al. Reduced red blood cell deformability, an indicator for high fetal or maternal risk, is found in preeclampsia and IUGR. Hypertens Pregnancy 21(2):147-60 (2002).
- G. V. Grigorev, A. V. Lebedev, X. Wang, et al. Advances in Microfluidics for Single Red Blood Cell Analysis. Biosensors, 13, 117 (2023).
- Y. J. Kang. Microfluidic-based effective monitoring of bloods by measuring RBC aggregation and blood viscosity under stepwise varying shear rates. Korea Aust. Rheol. J., 32, 15–27 (2020).
- R. Mehri, C. Mavriplis, M. Fenech. Controlled microfluidic environment for dynamic investigation of red blood cell aggregation. J. Vis. Exp. (100):e52719 (2015).
- V. Pretini, M. H. Koenen, L. Kaestner, et al. Red Blood Cells: Chasing Interactions. Front Physiol. 10: 945 (2019).
- P. Gresele, R. Guerciolini, G. G. Nenci. Erythrocyte deformability changes in normal pregnancy and pre-eclampsia. Br J Haematol. 52(2):340-2 (1982).
- T. C. Inglis, J. Stuart, A. J. George, A. J. Davies. Haemostatic and rheological changes in normal pregnancy and pre-eclampsia. Br J Haematol. 50(3):461-5 (1982).
- J. Thorburn, M. M. Drummond, K. A. Whigham. Blood viscosity and haemostatic factors in late pregnancy, pre-eclampsia and fetal growth retardation. Br J Obstet Gynaecol. 89(2):117-22 (1982).
- A. Alexandrova-Watanabe. Study of rheological, mechanical and morphological properties of blood, its formal elements and parameters of hemocoagulation in type 2 diabetes mellitus. Ph.D. thesis, Institute of Mechanics, Bulgarian Academy of Sciences, Sofia, Bulgaria (2021).
- A. Langari, V. Strijkova, R. Komsa-Penkova, et al. Morphometric and Nanomechanical Features of Erythrocytes Characteristic of Early Pregnancy Loss. Int. J. Mol. Sci., 23, 4512 (2022).
- V. Sergunova, S. Leesment, A. Kozlov, et al. Investigation of Red Blood Cells by Atomic Force Microscopy. Sensors 22, 2055 (2022).
- M. E. Dokukin, N. V. Guz, I. Sokolov. Quantitative study of the elastic modulus of loosely attached cells in AFM indentation experiments. Biophysical Journal 104, 2123-2131 (2013).
- C. G. Conant, M. A. Schwartz, J. E. Beecher, et al. Well plate microfluidic system for investigation of dynamic platelet behavior under variable shear loads. Biotechnol Bioeng 108: 2978 2987 (2011).
- S. Dinarelli, G. Longo, G. Dietler, et al. Erythrocyte’s aging in microgravity highlights how environmental stimuli shape metabolism and morphology. Sci. Rep. 8, 5277 (2018).
- B. Briscoe, K. Sebastian, M. Adams, The effect of indenter geometry on the elastic response to indentation. J. Phys. D Appl. Phys. 27, 1156–1162 (1994).
- H. Valensise, B. Vasapollo, G. Gagliardi, G. P. Novelli Early and late preeclampsia: two different maternal hemodynamic states in the latent phase of the disease. Hypertension 52: 873– 880 (2008).
- M. A. R. de Freitas, A. V. da Costa, L. A. Medeiros, et al. The role of the erythrocyte in the outcome of pregnancy with preeclampsia. PloS ONE 14(3): e0212763 (2019).
- R. Gamzu, G. Barshtein, F. Tsipis, et al. Pregnancy-induced hypertension is associated with elevation of aggregability of red blood cells. Clin. Hemorheol. Microcirc. 27, 163–169 (2002).
- O. K. Baskurt, H. J. Meiselman, Erythrocyte aggregation: Basic aspects and clinical importance. Clin. Hemorheol. Microcirc. 53, 23–37 (2013).
- E. Friederichs, H. J. Meiselman, Effects of calcium permeabilization on RBC rheologic behavior. Biorheology 31, 207–215 (1994).