Sickle Cell Visualization In Vivo in Humans: Microvascular Occlusion Formation and Hemorheological Indices

Authors

• Marisa M Morakis
• Luojie Huang
• Gregory N. McKay
• Sophie Lanzkron, Thomas Jefferson UniversityFollow
• Lydia H. Pecker
• Nicholas J. Durr

Document Type

Article

Publication Date

3-4-2026

Comments

This article is the author's final published version in Blood Advances, Volume 10, Issue 12, 2026, Pages 4215 - 4226.

The published version is available at https://doi.org/10.1182/bloodadvances.2025018716. Copyright © 2026 American Society of Hematology.

Abstract

Vaso-occlusion is a signature pathology of sickle cell disease (SCD). However, the lack of in vivo methods to observe individual blood cell dynamics in humans limits our understanding of occlusion formation mechanisms. We present a novel in vivo, noninvasive, label-free, and high-resolution imaging technique to study blood flow and sickled cell behavior in affected individuals. We used oblique back-illumination microscopy (OBM) to capture videos of 91.0 ± 42.3 sublingual capillaries in each of 10 participants with SCD before and after red cell transfusions and compared the measurements to 10 unaffected controls. With direct observation of blood cell activity, we identified microvascular occlusions initiated by red blood cells (RBCs) that adhered to the endothelium and caused mechanical vessel obstruction. Often, the RBCs were sickled. Then, in each observed vessel, we classified blood flow as fast, slow, or no flow and counted adhered RBCs. Compared to controls, patients with SCD before transfusion had fewer fast-flowing vessels (48.7% vs 77.7%; P = 5.8 × 10-4), more no flow vessels (16.1% vs 2.4%; P = .0010), and more adhered RBCs (1.37 vs 0.01 cells per vessel; P = .0025). From before to after transfusion, SCD microvasculature had increased fast-flowing (48.7% vs 65.8%; P = .0098) and decreased no flow vessels (16.1% vs 6.0%; P = .0039); adhered RBCs decreased (1.37 vs 0.71 cells per vessel; P = .043). These hemorheological indices captured transfusion-induced changes to vascular dynamics and events leading to microvascular dysfunction and occlusion in SCD. Our findings demonstrate the potential of OBM to study vaso-occlusion pathobiology, accelerate therapeutic evaluation, and personalize treatment strategies in people with SCD.

Recommended Citation

Morakis, Marisa M; Huang, Luojie; McKay, Gregory N.; Lanzkron, Sophie; Pecker, Lydia H.; and Durr, Nicholas J., "Sickle Cell Visualization In Vivo in Humans: Microvascular Occlusion Formation and Hemorheological Indices" (2026). Cardeza Foundation for Hematologic Research. Paper 106.
https://jdc.jefferson.edu/cardeza_foundation/106

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Language

English