Abstracts

MECHANICAL FRAGILITY

GBT1118, A Voxelotor Analog, Protects Red Blood Cells From Damage During Severe Hypoxia

Michael Tarasev, Marta Ferranti, Andrew Herppich, Patrick Hines
A lack of objective metrics in Sickle Cell Disease (SCD) makes it difficult to assess individual patient therapy options or assess the effects of therapy. This is further complicated by mechanisms of action involving multiple interconnected effects, that combine to relieve SCD symptoms.

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MECHANICAL FRAGILITY

Whole Blood Adhesion to VCAM-1 and P-Selectin and RBC Mechanical Fragility Can be Compromised in Long COVID-19 Patients with Sickle Cell Disease

M.Tarasev, M. Ferranti, C. Allen, X. Gao, K. Topping, B. Makinde-Odesola, L. Bronté-Hall, and P.Hines. Functional Fluidics, Detroit, MI, Wayne State University, Detroit, MI, The Foundation for Sickle Cell Disease Research, Hollywood, FL
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause severe vascular complications associated with endothelial dysfunction and systemic inflammation. COVID19-specific IgG are detectable within a week of infection. Long-COVID has been described in patients continuing to exhibit including fatigue, dyspnea, headache, and brain fog. The recent FAIR Health study reported that 23.2% had at least one post-COVID symptom [1]. The underlying biologic mechanisms of Long-COVIDremain unclear, thus treatments are limited to symptomatic relief and supportive care. Many long COVID symptoms are consistent with systemic inflammation and impaired oxygen delivery observed in individuals with sickle cell disease (SCD), in turn associated with elevated blood cell adhesion and decreased red blood cell (RBC) stability.

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MECHANICAL FRAGILITY

pRBC Membrane Fragility as a Potential Storage Time-Independent Quality Metric

Tarasev M, Alfano K, Chakraborty S, Bertholf M, Zubair A. Blaze Medical Devices, Ann Arbor, MI, Ashburn the Blood Alliance, inc., Jacksonville, FL, Ashburn Mayo Clinic, Jacksonville, FL, Ashburn
The effect red blood cell (RBC) storage and ‘storage lesion’ (‘new’ vs ‘old’ blood) has on transfusion efficacy and outcomes remains the subject of a considerable debate. However, focusing on storage time as the sole metric for RBC viability loss ignores the variability in properties of RBC even of the same age.

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MECHANICAL FRAGILITY

Plasma Composition Effects On Mechanical Fragility Of Packed Red Blood Cells

Tarasev M, Chakraborty S, and Davenport R. Blaze Medical Devices, Ann Arbor, MI, United States of America, University of Michigan, Ann Arbor, MI, United States of America
Packed Red Blood Cell (pRBC) ability to deform and to withstand mechanical stress without hemolysis is vitally important for post-transfusion cell survival and their participation in microcirculation

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FLOW ADHESION

Adhesion To VCAM-1 and P-Selectin Predict Time-To-Resolve (TTR) Of Vaso-Occlusive Crisis

Michael Tarasev, Xiufeng Gao, Jennell White, Patrick Hines
Sickle cell disease (SCD) is characterized by frequent and unpredictable vaso-occlusive crises (VOCs) resulting in increased morbidity and mortality. There are no reliable biomarkers to predict the onset and progression of VOCs, complicating disease management

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MECHANICAL FRAGILITY

Evaluation of Coagulation and Inflammatory Markers in Pediatric Patients on Extracorporeal Membrane Oxygenation (ECMO)

Regling K, DO , Cashen K , Gadgeel M, Xi Y, Herppich A,Tarasev M, Hines P, Chitlur M, Blood (2020) 136 (Supplement 1): 14.
Bleeding and thrombosis remain the primary complications related to the use of extracorporeal membrane oxygenation (ECMO). To date, no single test or parameter has been identified to accurately predict the risk of these hemostatic complications. Thrombin generation may be the key marker for both thrombosis and bleeding, and may be influenced by inflammation.

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FLOW ADHESION

A Longitudinal Study to Identify and Assess Adhesion Indices during Vaso-Occlusive Crises in Adults and Adolescents with Sickle Cell Disease

White J, Liu K, Gao X, Callaghan M, Hines P. A Longitudinal Study to Identify and Assess Adhesion Indices during Vaso-Occlusive Crises in Adults and Adolescents with Sickle Cell Disease. Blood 2018; 132 (Supplement 1): 1097. doi:
The decision to seek medical contact varies amongst patients. When VOCs are managed at home valuable information remains unknown. We designed a longitudinal, observational study to capture adhesion data at home and in a hospital setting. The objective of this study was to determine whether a standardized, flow-based adhesion bioassay is capable of identifying VOCs occurring in SCD patients with varying degrees of medical contact

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FLOW ADHESION

Longitudinal Evaluation of a Standardized P-Selectin Flow Adhesion Bioassay: Potential Role for the Assessment and Prediction of Vaso-Occlusive Episodes in Sickle Cell Disease

We developed a standardized, flow-based adhesion assay to measure p-selectin mediated adhesion in SCD. Whole blood (Wb) and isolated WBC samples were perfused (1.0 dynes/cm2, 1.67Hz) through micro-fluidic channels

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FLOW ADHESION

Increased Erythrocyte Adhesion to VCAM-1 During Pulsatile Flow: Application of a Microfluidic Flow Adhesion Bioassay

White J, Lancelot M, Sarnaik S, Hines P. Increased erythrocyte adhesion to VCAM-1 during pulsatile flow: Application of a microfluidic flow adhesion bioassay. Clin Hemorheol Microcirc. 2015;60(2):201-13. doi: 10.3233/CH-141847. PMID: 24898561; PMCID: PMC4923762.
Sickle cell disease (SCD) is characterized by microvascular occlusion mediated by adhesive interactions of sickle erythrocytes (SSRBCs) to the endothelium. Most in vitroflow adhesion assays measure SSRBC adhesion during continuous flow, although in vivoSSRBC adhesive interactions occur during pulsatile flow. Using a well-plate microfluidic flow adhesion system, we demonstrate that isolated SSRBCs adhere to vascular cell adhesion molecule (VCAM-1) at greater levels during pulsatile versus continuous flow.

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MECHANICAL FRAGILITY

Variability in Individual Response to a Single Sickling Event for Normal, Sickle Cell, and Sickle-Trait Erythrocytes

Chakraborty, S., Muchnik, M., Light, L., Alfano, K. and Tarasev, M, Featured Presentation at the 2014 Annual AABB Meeting, October 2014, Philadelphia, PA, Transfusion, Volume 54S, p. 183A
Hemoglobin S (Hb-S) polymerization is the primary event in sickle cell disease causing irreversible damage to red blood cell (RBC) membranes over repeated polymerization cycles. A single polymerization triggered by a hypoxic environment was reported to result in reversibly (upon reoxygenation) decreased RBC deformability and increased mechanical fragility (MF). Individualized responses have not been reported, although RBC fragility can vary significantly even among healthy individuals. This study evaluates individual variability in response to a single hypoxia-induced sickling event, through changes in RBC MF.

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MECHANICAL FRAGILITY

RBC Membrane Fragility as an Age-Independent Metric of Stored Blood Quality

Tarasev M, Alfano K, Chakraborty S, Bertholf M, ZubairA, Blaze Medical Devices, Ann Arbor, MI, Ashburn Mayo Clinic, Jacksonville, FL, Ashburn, May 2012 Conference: Canadian Society for Transfusion Medicine (SCTM)
Long storage times for blood products are often unavoidable. Product age is essentially the only indicator used today for Red Blood Cell (RBC) quality loss during storage. Much controversy persists over the impact of RBC age on transfusion outcomes, as studies on this issue remain inconclusive.

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MECHANICAL FRAGILITY

Increasing Transfusion Efficacy of Stored Blood by using Quality-Based Alternatives to First-In-First-Out Inventory Planning

Beeker, A., Metzger, P., Moldawer, D., Tarasev, M., Alfano, K., Presentation at the 2011 Annual Meeting of the Society for the Advancement of Blood Management (SABM), Philadelphia, PA, September 2011; Blood Transfusion (2011) Volume 9, Number s5, page s1
The effect of red blood cell (RBC) storage on transfusion efficacy is a topic of considerable debate. While significant data exist linking "older" blood to "worse" outcomes, other studies question any such correlation.

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MECHANICAL FRAGILITY

Evaluation of Novel In-Vitro RBC Fragility Metrics as Age-Independent Measures of Stored RBC Quality

Tarasev, M., Alfano, K., Chakraborty, S., Zubair, A., Presentation at the 2011 Annual American: Association of Blood Banks (AABB) Meeting, October 2011, San Diego, CA; Transfusion (2011) Volume 51s, page 79
Background/Case Studies: The effect of red blood cell (RBC) “storage lesion” is a topic of much debate, especially regarding whether or not “older” blood provides lower transfusion efficacy. However, focusing on storage time as the sole measure of storage lesion ignores the inherent variability in RBC properties. Both biological and physical differences have the potential to affect the scope and rates of changes in RBC quality during storage. We propose novel in-vitro RBC fragility metrics which, independent of storage duration, can be used to assess stored RBC quality.

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