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Could the phenomenon of catch bonding-force-strengthened cellular adhesion-play a role in sickle cell disease, where abnormal red blood cell (RBC) adhesion obstructs blood flow? Here, we investigate the dynamics of sickle RBCs adhering to a surface functionalized with the protein laminin (a component of the extracellular matrix around blood vessels) under physiologically relevant microscale flow. First, using total internal reflectance microscopy we characterize the spatial fluctuations of the RBC membrane above the laminin surface before detachment. The complex dynamics we observe suggest the possibility of catch bonding, where the mean detachment time of the cell from the surface initially increases to a maximum and then decreases as a function of shear force. We next conduct a series of shear-induced detachment experiments on blood samples from 25 sickle cell disease patients, quantifying the number and duration of adhered cells under both sudden force jumps and linear force ramps. The experiments reveal that a subset of patients does indeed exhibit catch bonding. By fitting the data to a theoretical model of the bond dynamics, we can extract the mean bond lifetime versus force for each patient. The results show a striking heterogeneity among patients, both in terms of the qualitative behavior (whether or not there is catch bonding) and in the magnitudes of the lifetimes. Patients with large bond lifetimes at physiological forces are more likely to have certain adverse clinical features, like a diagnosis of pulmonary arterial hypertension and intracardiac shunts. By introducing an in vitro platform for fully characterizing RBC-laminin adhesion dynamics, our approach could contribute to the development of patient-specific antiadhesive therapies for sickle cell disease. The experimental setup is also easily generalizable to studying adhesion dynamics in other cell types, for example, leukocytes or cancer cells, and can incorporate disease-relevant environmental conditions like oxygen deprivation., Competing Interests: Declaration of interests R.A., J.A.L., U.A.G., and Case Western Reserve University have financial interests in Hemex Health Inc. J.A.L., U.A.G., and Case Western Reserve University have financial interests in BioChip Labs Inc. U.A.G. and Case Western Reserve University have financial interests in Xatek Inc. U.A.G. has financial interests in DxNow Inc. Financial interests include licensed intellectual property, stock ownership, research funding, employment, and consulting. Hemex Health Inc. offers point-of-care diagnostics for hemoglobin disorders, anemia, and malaria. BioChip Labs Inc. offers commercial clinical microfluidic biomarker assays for inherited or acquired blood disorders. Xatek Inc. offers point-of-care global assays to evaluate the hemostatic process. DxNow Inc. offers microfluidic and bio-imaging technologies for in vitro fertilization, forensics, and diagnostics. Competing interests of Case Western Reserve University employees are overseen and managed by the Conflict of Interests Committee according to a Conflict-of-Interest Management Plan., (Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.)