Valerie Tutwiler1, Rustem I Litvinov1,2, Anna Protopopova1, Chandrasekaran Nagaswami1, Carlos Villa3, Eric Woods4, Osheiza Abdulmalik5, Don L Siegel3, J Eric Russell6, Vladimir R Muzykantov7, Wilbur A Lam8, David R Myers8, John W Weisel1. 1. Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. 2. Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation. 3. Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. 4. Max-Planck-Institut für Eisenforschung GmbH Düsseldorf, Düsseldorf, Germany. 5. Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. 6. Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. 7. Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA. 8. The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory University, Atlanta, Georgia, USA.
Abstract
BACKGROUND: Blood clot contraction, volume shrinkage of the clot, is driven by platelet contraction and accompanied by compaction of the erythrocytes and their gradual shape change from biconcave to polyhedral, with the resulting cells named polyhedrocytes. OBJECTIVES: Here, we examined the role of erythrocyte rigidity on clot contraction and erythrocyte shape transformation. METHODS: We used an optical tracking methodology that allowed us to quantify changes in contracting clot size over time. RESULTS AND CONCLUSIONS: Erythrocyte rigidity has been shown to be increased in sickle cell disease (SCD), and in our experiments erythrocytes from SCD patients were 4-fold stiffer than those from healthy subjects. On average, the final extent of clot contraction was reduced by 53% in the clots from the blood of patients with SCD compared to healthy individuals, and there was significantly less polyhedrocyte formation. To test if this reduction in clot contraction was due to the increase in erythrocyte rigidity, we used stiffening of erythrocytes via chemical cross-linking (glutaraldehyde), rigidifying Wrightb antibodies (Wrb ), and naturally more rigid llama ovalocytes. Results revealed that stiffening erythrocytes result in impaired clot contraction and fewer polyhedrocytes. These results demonstrate the role of erythrocyte rigidity in the contraction of blood clots and suggest that the impaired clot contraction/shrinkage in SCD is due to the reduced erythrocyte deformability, which may be an underappreciated mechanism that aggravates obstructiveness of erythrocyte-rich (micro)thrombi in SCD.
BACKGROUND: Blood clot contraction, volume shrinkage of the clot, is driven by platelet contraction and accompanied by compaction of the erythrocytes and their gradual shape change from biconcave to polyhedral, with the resulting cells named polyhedrocytes. OBJECTIVES: Here, we examined the role of erythrocyte rigidity on clot contraction and erythrocyte shape transformation. METHODS: We used an optical tracking methodology that allowed us to quantify changes in contracting clot size over time. RESULTS AND CONCLUSIONS: Erythrocyte rigidity has been shown to be increased in sickle cell disease (SCD), and in our experiments erythrocytes from SCD patients were 4-fold stiffer than those from healthy subjects. On average, the final extent of clot contraction was reduced by 53% in the clots from the blood of patients with SCD compared to healthy individuals, and there was significantly less polyhedrocyte formation. To test if this reduction in clot contraction was due to the increase in erythrocyte rigidity, we used stiffening of erythrocytes via chemical cross-linking (glutaraldehyde), rigidifying Wrightb antibodies (Wrb ), and naturally more rigid llama ovalocytes. Results revealed that stiffening erythrocytes result in impaired clot contraction and fewer polyhedrocytes. These results demonstrate the role of erythrocyte rigidity in the contraction of blood clots and suggest that the impaired clot contraction/shrinkage in SCD is due to the reduced erythrocyte deformability, which may be an underappreciated mechanism that aggravates obstructiveness of erythrocyte-rich (micro)thrombi in SCD.
Authors: Tamas Alexy; Jon Detterich; Philippe Connes; Kalman Toth; Elie Nader; Peter Kenyeres; Jose Arriola-Montenegro; Pinar Ulker; Michael J Simmonds Journal: Front Physiol Date: 2022-07-06 Impact factor: 4.755
Authors: Rafael R Khismatullin; Shahnoza Abdullayeva; Alina D Peshkova; Khetam Sounbuli; Natalia G Evtugina; Rustem I Litvinov; John W Weisel Journal: Blood Adv Date: 2022-03-22