Red blood cell mechanical sensitivity improves in patients with sickle cell disease undergoing chronic transfusion after prolonged, subhemolytic shear exposure

Simmonds, Michael J.; Suriany, Silvie; Ponce, Derek; Detterich, Jon

doi:10.1111/trf.14901

Cited by 11 publications

(5 citation statements)

References 35 publications

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“…This group has also published analysis of laboratory measurements of carbon monoxide and heme oxygenase for acute pain crisis prediction [41]. Other groups have studied red blood cell mechanical sensitivity and biomarker signatures of SCD severity [42,43]. The use of machine learning in a variety of areas of medicine including outcome prediction for chemoradiotherapy, breast cancer survival prediction, and early prediction of asthma exacerbations have recently been published [44-46].…”

Section: Discussionmentioning

confidence: 99%

Use of Mobile Health Apps and Wearable Technology to Assess Changes and Predict Pain During Treatment of Acute Pain in Sickle Cell Disease: Feasibility Study

Johnson¹,

Yang²,

Gollarahalli³

et al. 2019

JMIR Mhealth Uhealth

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BackgroundSickle cell disease (SCD) is an inherited red blood cell disorder affecting millions worldwide, and it results in many potential medical complications throughout the life course. The hallmark of SCD is pain. Many patients experience daily chronic pain as well as intermittent, unpredictable acute vaso-occlusive painful episodes called pain crises. These pain crises often require acute medical care through the day hospital or emergency department. Following presentation, a number of these patients are subsequently admitted with continued efforts of treatment focused on palliative pain control and hydration for management. Mitigating pain crises is challenging for both the patients and their providers, given the perceived unpredictability and subjective nature of pain.ObjectiveThe objective of this study was to show the feasibility of using objective, physiologic measurements obtained from a wearable device during an acute pain crisis to predict patient-reported pain scores (in an app and to nursing staff) using machine learning techniques.MethodsFor this feasibility study, we enrolled 27 adult patients presenting to the day hospital with acute pain. At the beginning of pain treatment, each participant was given a wearable device (Microsoft Band 2) that collected physiologic measurements. Pain scores from our mobile app, Technology Resources to Understand Pain Assessment in Patients with Pain, and those obtained by nursing staff were both used with wearable signals to complete time stamp matching and feature extraction and selection. Following this, we constructed regression and classification machine learning algorithms to build between-subject pain prediction models.ResultsPatients were monitored for an average of 3.79 (SD 2.23) hours, with an average of 5826 (SD 2667) objective data values per patient. As expected, we found that pain scores and heart rate decreased for most patients during the course of their stay. Using the wearable sensor data and pain scores, we were able to create a regression model to predict subjective pain scores with a root mean square error of 1.430 and correlation between observations and predictions of 0.706. Furthermore, we verified the hypothesis that the regression model outperformed the classification model by comparing the performances of the support vector machines (SVM) and the SVM for regression.ConclusionsThe Microsoft Band 2 allowed easy collection of objective, physiologic markers during an acute pain crisis in adults with SCD. Features can be extracted from these data signals and matched with pain scores. Machine learning models can then use these features to feasibly predict patient pain scores.

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Section: Discussionmentioning

confidence: 99%

Use of Mobile Health Apps and Wearable Technology to Assess Changes and Predict Pain During Treatment of Acute Pain in Sickle Cell Disease: Feasibility Study

Johnson¹,

Yang²,

Gollarahalli³

et al. 2019

JMIR Mhealth Uhealth

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“…When blood is exposed to very high levels of shear stress, overt cell rupture (ie, haemolysis) or impaired cellular deformability is typically observed. The subhemolytic threshold (ie, upper limits of functional tolerance of RBC) has only recently been described in healthy individuals 14,20 and those with sickle cell disease 33 ; thus, only limited studies have explored whether this threshold may be manipulated. A key finding of the present study was that venesection therapy led to a marked increase in the level of supraphysiological shear stress required to induce impairment in cellular deformability ( Figure 4); this is a positive finding, suggesting that the tolerance of HH RBCs to mechanical stress was improved with this therapy.…”

Section: Discussionmentioning

confidence: 99%

Mechanical sensitivity of red blood cells improves in individuals with hemochromatosis following venesection therapy

2020

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Background: Individuals with hereditary hemochromatosis (HH) receive frequent blood withdrawals (ie, venesections) as part of their primary treatment to assist in normalizing blood iron levels. It remains unclear whether this source of blood is suitable for use in blood product development, as current data indicate that red blood cell (RBC) deformability, both before and after shear stress exposure, is impaired in individuals with HH, relative to healthy controls. Given that venesection therapy is known to significantly reduce circulating iron levels in individuals with HH, the current study examined whether venesection therapy is effective at improving RBC mechanical properties, both before and after shear stress exposure, in individuals with HH. Study Design and Methods: Blood samples were initially collected from untreated HH patients (age, 61 ± 9 years; 14% female) undergoing their first venesection, and then again during their second (approx. 9 weeks later) and third (approx. 16 weeks later) venesections. RBC deformability was measured at each time point with a commercial ektacytometer. Moreover, to determine cell responses to mechanical stimuli, the mechanical sensitivity of blood samples was determined at each time point. Results: The salient findings indicate that venesection therapy used for managing plasma ferritin concentration significantly improves the cellular deformability of RBC in individuals with HH. Further, the sensitivity of RBC to supraphysiological mechanical stress is decreased (ie, improved) in a doseresponse fashion with routine venesection. Conclusion: While cellular mechanics of RBC from individuals with HH are impaired when untreated, venesection therapy significantly improves cellular properties of RBC, supporting the use of venesections in blood product development from individuals with well-managed HH. K E Y W O R D S hemorheology, iron overload, mechanical damage, RBC deformability, sublethal trauma Abbreviations: EI, elongation index; EI max , maximal theoretical elongation index at an infinite shear stress; HH, hereditary hemochromatosis; NO, nitric oxide; RBC-NOS, shear-sensitive nitric oxide synthase isoform; SS 1/2 , shear stress required to obtain half the EI max value.

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“…This interpretation is supported by the observation that measurements performed on the blood of SCD patients on HU exhibit an increase in RBC deformability after 12 months of therapy (EI increases from 0.14 ± 0.05 to 0.22 ± 0.07 at 3 Pa). 30 Red cell deformability also improves significantly in patients on chronic RBC transfusions compared to a non-transfused group, likely through the dilution of sickle RBCs with normal RBCs. 31 Patients with less deformable cells also commonly present with priapism, leg ulcers, and kidney disease potentially brought on by increased hemolysis of the rigid RBCs.…”

Section: Rbc Deformability: Point Of Sickling Elongation Indicesmentioning

confidence: 99%

Blood rheology biomarkers in sickle cell disease

Rab

Shevkoplyas

et al. 2020

Exp Biol Med (Maywood)

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Sickle cell disease (SCD) is the most common inherited blood disorder, affecting approximately 100,000 patients in the U.S. and millions more worldwide. Patients with SCD experience a wide range of clinical complications, including frequent pain crises, stroke, and early mortality, all originating from a single-point mutation in the β-globin subunit. The RBC changes resulting from the sickle mutation lead to a host of rheological abnormalities that diminish microvascular blood flow, and produce severe anemia due to RBC hemolysis, and ischemia from vaso-occlusion initiated by sticky, rigid sickle RBCs. While the pathophysiology and mechanisms of SCD have been investigated for many years, therapies to treat the disease are limited. In addition to RBC transfusion, there are only two US Food and Drug Administration (FDA)-approved drugs to ameliorate SCD complications: hydroxyurea (HU) and L-glutamine (Endari™). The only curative therapy currently available is allogeneic hematopoietic stem cell transplantation (HSCT), which is generally reserved for individuals with a matched related donor, comprising only 10–15% of the total SCD population. Potentially curative advanced gene therapy approaches for SCD are under investigation in ongoing clinical trials. The ultimate goal of any curative treatment should be to repair the hemorheological abnormalities caused by SCD, and thus normalize blood flow and prevent clinical complications. Our mini-review highlights a set of key hemorheological biomarkers (and the current and emerging technologies used to measure them) that may be used to guide the development of novel curative and palliative therapies for SCD, and functionally assess outcomes. Impact statement Severe impairment of blood rheology is the hallmark of SCD pathophysiology, and one of the key factors predisposing SCD patients to pain crises, organ damage, and early mortality. As novel therapies emerge to treat or cure SCD, it is crucial that these treatments are functionally evaluated for their effect on blood rheology. This review describes a comprehensive panel of rheological biomarkers, their clinical uses, and the technologies used to obtain them. The described technologies can produce highly sensitive measurements of the ability of current treatments to improve blood rheology of SCD patients. The goal of curative therapies should be to achieve blood rheology biomarkers measurements in the range of sickle cell trait individuals (HbAS). The use of the panel of rheological biomarkers proposed in this review could significantly accelerate the development, optimization, and clinical translation of novel therapies for SCD.

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Red blood cell mechanical sensitivity improves in patients with sickle cell disease undergoing chronic transfusion after prolonged, subhemolytic shear exposure

Cited by 11 publications

References 35 publications

Use of Mobile Health Apps and Wearable Technology to Assess Changes and Predict Pain During Treatment of Acute Pain in Sickle Cell Disease: Feasibility Study

Use of Mobile Health Apps and Wearable Technology to Assess Changes and Predict Pain During Treatment of Acute Pain in Sickle Cell Disease: Feasibility Study

Mechanical sensitivity of red blood cells improves in individuals with hemochromatosis following venesection therapy

Blood rheology biomarkers in sickle cell disease

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