Journal of Clinical Medicine

Research

11 pages, 297 KiB

Open AccessArticle

Early Strokes Are Associated with More Global Cognitive Deficits in Adults with Sickle Cell Disease

by Maryline Couette, Stéphanie Forté, Damien Oudin Doglioni, Armand Mekontso-Dessap, David Calvet, Kevin H. M. Kuo and Pablo Bartolucci

J. Clin. Med. 2023, 12(4), 1615; https://doi.org/10.3390/jcm12041615 - 17 Feb 2023

Cited by 5 | Viewed by 1521

Abstract

This study sought to link neurocognitive profiles in sickle cell disease (SCD) patients with clinical characteristics. We conducted a prospective cohort study of adults with SCD who underwent comprehensive neuropsychological assessment at the UMGGR clinic at Henri Mondor Hospital, Créteil (France). A cluster [...] Read more.

This study sought to link neurocognitive profiles in sickle cell disease (SCD) patients with clinical characteristics. We conducted a prospective cohort study of adults with SCD who underwent comprehensive neuropsychological assessment at the UMGGR clinic at Henri Mondor Hospital, Créteil (France). A cluster analysis was performed based on neuropsychological testing scores. The association between clusters and clinical profiles was assessed. Between 2017 and 2021, 79 patients with a mean age of 36 [range 19–65] years were included. On principal component analysis, a 5-factor model presented the best fit (Bartlett’s sphericity test [χ² (171) = 1345; p < 0.001]), explaining 72% of the variance. The factors represent distinct cognitive domains and anatomical regions. On hierarchical classification, three clusters emerged. Cluster 1 (n = 24) presented deficits in all five factors compared to Cluster 3 (n = 33). Cluster 2 (n = 22) had deficits in all factors, but to a lesser extent than Cluster 1. MoCA scores mirrored the severity of these cognitive deficits. Age, genotype and stroke prevalence did not differ significantly between clusters. However, the time of first stroke occurrence differed significantly between Cluster 1 and 2–3: 78% of strokes occurred during childhood, whereas 80% and 83% occurred during adulthood in Clusters 2 and 3, respectively. Educational attainment was also reduced in Cluster 1. SCD patients with childhood stroke seem to be at increased risk of a global cognitive deficit profile. In addition to existing methods of primary and secondary stroke prevention, early neurorehabilitation should be prioritized in order to reduce the long-term cognitive morbidity of SCD. Full article

(This article belongs to the Special Issue Acute and Chronic Sickle Cell Disease: Causes, Consequences, and Treatment)

15 pages, 1599 KiB

Open AccessArticle

Real-World Evidence on Disease Burden and Economic Impact of Sickle Cell Disease in Italy

by Lucia De Franceschi, Chiara Castiglioni, Claudia Condorelli, Diletta Valsecchi, Eleonora Premoli, Carina Fiocchi, Valentina Perrone, Luca Degli Esposti, Gian Luca Forni and on behalf of the GREATalyS Study Group

J. Clin. Med. 2023, 12(1), 117; https://doi.org/10.3390/jcm12010117 - 23 Dec 2022

Cited by 1 | Viewed by 1946

Abstract

A real-world analysis was conducted in Italy among sickle cell disease (SCD) patients to evaluate the epidemiology of SCD, describe patients’ characteristics and the therapeutic and economic burden. A retrospective analysis of administrative databases of various Italian entities was carried out. All patients [...] Read more.

A real-world analysis was conducted in Italy among sickle cell disease (SCD) patients to evaluate the epidemiology of SCD, describe patients’ characteristics and the therapeutic and economic burden. A retrospective analysis of administrative databases of various Italian entities was carried out. All patients with ≥1 hospitalization with SCD diagnosis were included from 01/2010-12/2017 (up to 12/2018 for epidemiologic analysis). The index date corresponded to the first SCD diagnosis. In 2018, SCD incidence rate was 0.93/100,000, the prevalence was estimated at 13.1/100,000. Overall, 1816 patients were included. During the 1st year of follow-up, 50.7% of patients had one all-cause hospitalization, 27.8% had 2, 10.4% had 3, and 11.1% had ≥4. Over follow-up, 6.1–7.2% of patients were treated with SCD-specific, 58.4–69.4% with SCD-related, 60.7–71.3% with SCD-complications-related drugs. Mean annual number per patient of overall treatments was 14.9 ± 13.9, hospitalizations 1.1 ± 1.1, and out-patient services 5.3 ± 7.6. The total mean direct cost per patient was EUR 7918/year (EUR 2201 drugs, EUR 3320 hospitalizations, and EUR 2397 out-patient services). The results from this real-world analysis showed a high disease burden for SCD patients with multiple hospitalizations during the follow-up. High healthcare resource utilization and costs were associated with patient’ management and were most likely underestimated since indirect costs and Emergency Room admissions were not included. Full article

(This article belongs to the Special Issue Acute and Chronic Sickle Cell Disease: Causes, Consequences, and Treatment)

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14 pages, 734 KiB

Open AccessArticle

Echocardiographic Evaluation in Paediatric Sickle Cell Disease Patients: A Pilot Study

by Letizia Sabatini, Marcello Chinali, Alessio Franceschini, Margherita Di Mauro, Silvio Marchesani, Francesca Fini, Giorgia Arcuri, Mariachiara Lodi, Giuseppe Palumbo and Giulia Ceglie

J. Clin. Med. 2023, 12(1), 7; https://doi.org/10.3390/jcm12010007 - 20 Dec 2022

Cited by 2 | Viewed by 1316

Abstract

Cardiovascular involvement has a great impact on morbidity and mortality in sickle cell disease (SCD). Currently, few studies are available regarding the paediatric setting and, moreover, current guidelines for the echocardiogram screening program in the asymptomatic paediatric population are controversial. We performed a [...] Read more.

Cardiovascular involvement has a great impact on morbidity and mortality in sickle cell disease (SCD). Currently, few studies are available regarding the paediatric setting and, moreover, current guidelines for the echocardiogram screening program in the asymptomatic paediatric population are controversial. We performed a retrospective observational monocentric study on 64 SCD patients (37 male and 27 female, median age 10) at the Bambino Gesù Childrens’ Hospital, who had undergone a routine transthoracic echocardiogram. In total, 46 (72%) patients had at least one cardiac abnormality. Left atrial dilatation (LAD) was present in 41 (65%) patients and left ventricular hypertrophy (LVH) was found in 29 (45%) patients. Patients with LAD showed lower median haemoglobin levels (p = 0.009), and a higher absolute reticulocyte count (p = 0.04). LVH was negatively correlated with the median haemoglobin value (p = 0.006) and positively with the reticulocyte count (p = 0.03). Moreover, we found that patients with cardiac anomalies had higher transfusion needs and a lower frequency of pain crises. In our setting, cardiac involvement has a high prevalence in the paediatric cohort and seems to be associated with specific laboratory findings, and with a specific clinical phenotype characterized by complications related to high haemodynamic load. Full article

(This article belongs to the Special Issue Acute and Chronic Sickle Cell Disease: Causes, Consequences, and Treatment)

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6 pages, 385 KiB

Open AccessArticle

Should Magnetic Resonance Angiography Be Used for Screening of Intracranial Aneurysm in Adults with Sickle Cell Disease?

by Igor Gomes Padilha, François Guilbert, Laurent Létourneau-Guillon, Stéphanie Forté, Kristoff Nelson, Manon Bélair, Jean Raymond and Denis Soulières

J. Clin. Med. 2022, 11(24), 7463; https://doi.org/10.3390/jcm11247463 - 16 Dec 2022

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Abstract

Magnetic resonance imaging (MRI) is used in patients with sickle cell disease (SCD) to detect silent cerebral infarcts. MR angiography (MRA) can identify arterial stenoses and intracranial aneurysms (ICANs) associated with SCD. In this study, we aimed to estimate the prevalence of ICANs [...] Read more.

Magnetic resonance imaging (MRI) is used in patients with sickle cell disease (SCD) to detect silent cerebral infarcts. MR angiography (MRA) can identify arterial stenoses and intracranial aneurysms (ICANs) associated with SCD. In this study, we aimed to estimate the prevalence of ICANs in asymptomatic adult patients with SCD referred from the SCD clinic for routine screening by MRI/MRA using a 3T-MRI scanner. Findings were independently reviewed by two neuroradiologists. Between 2016 and 2020, 245 asymptomatic adults with SCD were stratified according to genotype (SS/S-β0thalassemia and SC/Sβ+). ICANs were found in 27 patients (11%; 0.95 CI: 8–16%). ICANs were more frequent in SS/S-β0thalassemia patients (20/118 or 17%; 0.95 CI: 11–25%) than in SC/βb+ patients (7/127 or 6%; 0.95 CI: 2–11%; p = 0.007). Individuals with SCD (particularly SS/S-β0thalassemia) have a higher prevalence of ICANs than the general population. We believe that MRA should be considered in the current American Society of Hematology guidelines, which already contain a recommendation for MRI at least once in adult SCD patients. However, the clinical significance of preventive treatment of unruptured aneurysms remains controversial. Full article

(This article belongs to the Special Issue Acute and Chronic Sickle Cell Disease: Causes, Consequences, and Treatment)

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6 pages, 209 KiB

Open AccessArticle

Pitfalls in Diagnosing Thrombotic Thrombocytopenic Purpura in Sickle Cell Disease

by Dimitris A. Tsitsikas, Diana Mihalca, John Hall, Jori E. May, Radhika Gangaraju, Marisa B. Marques and Marie Scully

J. Clin. Med. 2022, 11(22), 6676; https://doi.org/10.3390/jcm11226676 - 10 Nov 2022

Viewed by 1255

Abstract

Thrombotic thrombocytopenia purpura is characterised by microangiopathic haemolytic anaemia and red cell fragmentation on the peripheral smear, neurological involvement and thrombocytopenia. Diagnosis in the context of sickle cell disease can be challenging due to the inherent haemolytic state and the multitude of other [...] Read more.

Thrombotic thrombocytopenia purpura is characterised by microangiopathic haemolytic anaemia and red cell fragmentation on the peripheral smear, neurological involvement and thrombocytopenia. Diagnosis in the context of sickle cell disease can be challenging due to the inherent haemolytic state and the multitude of other associated complications of the latter. Specifically, fat embolism syndrome characterised by respiratory failure, neurological impairment and thrombocytopenia can be misdiagnosed this way. Confirmation of a diagnosis of thrombotic thrombocytopenic purpura requires demonstration of very low levels (<10%) of the metalloproteinase ADAMTS13 which in fat embolism syndrome is normal. Existing scoring systems used to estimate the pre-test probability for thrombotic thrombocytopenic purpura cannot be applied in patients with sickle cell disease due to the chronic underlying haemolysis. Here, we analyse the diagnostic approach in published cases of thrombotic thrombocytopenic purpura affecting patients with sickle-cell disease. The vast majority of cases were characterised by severe respiratory failure before any other manifestation, a feature of fat embolism syndrome but not of thrombotic thrombocytopenic purpura, and all received red cell transfusion prior to receiving therapeutic plasma exchange. Despite the potential overestimation of the pre-test probability using the existing scoring systems, a large number of cases still scored low. There were no cases with documented low ADAMTS13. In the majority this was not tested, while in the 3 cases that ADAMTS13 was tested, levels were normal. Our review suggests that due to many overlapping clinical and laboratory features thrombotic thrombocytopenic purpura may be erroneously diagnosed in sickle cell disease instead of other complications such as fat embolism syndrome and confirmation with ADAMTS13 testing is essential. Full article

(This article belongs to the Special Issue Acute and Chronic Sickle Cell Disease: Causes, Consequences, and Treatment)

11 pages, 562 KiB

Open AccessArticle

Risks and Benefits of Prophylactic Transfusion before Cholecystectomy in Sickle Cell Disease

by Elise Rambaud, Brigitte Ranque, Sofia Tsiakyroudi, Laure Joseph, Nathalie Bouly, Richard Douard, Anne François, Jacques Pouchot and Jean-Benoît Arlet

J. Clin. Med. 2022, 11(14), 3986; https://doi.org/10.3390/jcm11143986 - 09 Jul 2022

Cited by 2 | Viewed by 1540

Abstract

Preoperative transfusion (PT) reduces acute postoperative vaso-occlusive events (VOE) in sickle cell disease (SCD), but exposes patients to alloimmunization, encouraging a recent trend towards transfusion sparing. The aim of this study was to investigate the benefit–risk ratio of PT before cholecystectomy on the [...] Read more.

Preoperative transfusion (PT) reduces acute postoperative vaso-occlusive events (VOE) in sickle cell disease (SCD), but exposes patients to alloimmunization, encouraging a recent trend towards transfusion sparing. The aim of this study was to investigate the benefit–risk ratio of PT before cholecystectomy on the occurrence of postoperative VOE. Adult SCD patients who underwent cholecystectomy between 2008 and 2019 in our center were included. Patients’ characteristics, collected retrospectively, were compared according to PT. A total of 79 patients were included, 66% of whom received PT. Gallbladder histopathology found chronic cholecystitis (97%) and gallstones (66%). Transfused patients underwent more urgent surgeries and had experienced more painful vaso-occlusive crises (VOC) in the month before surgery (p = 0.05). Four (8.5%) post-transfusion alloimmunizations occurred, and two of them caused a delayed hemolytic transfusion reaction (DHTR) (4.3%). The occurrence of postoperative VOE was similar between the groups (19.2% vs. 29.6%, p = 0.45). Though not statistically significant, a history of hospitalized VOC within 6 months prior to surgery seemed to be associated to postoperative VOE among non-transfused patients (75% vs. 31.6%, p = 0.10). PT before cholecystectomy exposes to risks of alloimmunization and DHTR that could be avoided in some patients. Recent VOCs appear to be associated with a higher risk of postoperative VOE and prompt the preemptive transfusion of these patients. Full article

(This article belongs to the Special Issue Acute and Chronic Sickle Cell Disease: Causes, Consequences, and Treatment)

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12 pages, 1322 KiB

Open AccessArticle

Prophylactic Hydroxyurea Treatment Is Associated with Improved Cerebral Hemodynamics as a Surrogate Marker of Stroke Risk in Sickle Cell Disease: A Retrospective Comparative Analysis

by Brian R. Peine, Michael U. Callaghan, Joseph H. Callaghan and Alexander K. Glaros

J. Clin. Med. 2022, 11(12), 3491; https://doi.org/10.3390/jcm11123491 - 17 Jun 2022

Cited by 3 | Viewed by 1525

Abstract

Sickle cell disease (SCD) increases the incidence of childhood stroke eighty-fold. Stroke risk can be estimated by measurement of the blood velocity through the middle cerebral artery (MCA) using transcranial doppler ultrasound (TCD). A high MCA blood velocity indicates increased stroke risk due [...] Read more.

Sickle cell disease (SCD) increases the incidence of childhood stroke eighty-fold. Stroke risk can be estimated by measurement of the blood velocity through the middle cerebral artery (MCA) using transcranial doppler ultrasound (TCD). A high MCA blood velocity indicates increased stroke risk due to cerebral vasculopathy, and first-line treatment to prevent primary or recurrent strokes in high-risk children with SCD has classically been chronic blood transfusions. Research has more recently shown that many of these patients may safely transition from transfusions to oral hydroxyurea (HU) treatment while maintaining a decreased risk of stroke. However, the effect on stroke risk of truly prophylactic HU treatment beginning in infancy, prior to the onset of cerebral vasculopathy, is less well understood. Our retrospective study aimed to document the long-term effects of HU treatment compared with no HU treatment in children with SCD, using TCD measurements as our primary outcome and a surrogate marker of stroke risk. Our results showed that when accounting for age-related variability and duration of treatment, prophylactic HU treatment was independently associated with lower TCD MCA velocities compared with no HU treatment, providing further evidence supporting its early initiation for patients with SCD. Full article

(This article belongs to the Special Issue Acute and Chronic Sickle Cell Disease: Causes, Consequences, and Treatment)

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17 pages, 565 KiB

Open AccessArticle

In-Depth Immunological Typization of Children with Sickle Cell Disease: A Preliminary Insight into Its Plausible Correlation with Clinical Course and Hydroxyurea Therapy

by Giulia Giulietti, Daniele Zama, Francesca Conti, Mattia Moratti, Maria Teresa Presutti, Tamara Belotti, Maria Elena Cantarini, Elena Facchini, Mirna Bassi, Paola Selva, Elisabetta Magrini, Marcello Lanari and Andrea Pession

J. Clin. Med. 2022, 11(11), 3037; https://doi.org/10.3390/jcm11113037 - 27 May 2022

Cited by 1 | Viewed by 1533

Abstract

Sickle cell disease (SCD) is a condition of functional hypo-/a-splenism in which predisposition to bacterial infections is only a facet of a wide spectrum of immune-dysregulation disorders forming the clinical expression of a peculiar immunophenotype. The objective of this study was to perform [...] Read more.

Sickle cell disease (SCD) is a condition of functional hypo-/a-splenism in which predisposition to bacterial infections is only a facet of a wide spectrum of immune-dysregulation disorders forming the clinical expression of a peculiar immunophenotype. The objective of this study was to perform an in-depth immunophenotypical characterization of SCD pediatric patients, looking for plausible correlations between immunological biomarkers, the impact of hydroxyurea (HU) treatment and clinical course. This was an observational case–control study including 43 patients. The cohort was divided into two main groups, SCD subjects (19/43) and controls (24/43), differing in the presence/absence of an SCD diagnosis. The SCD group was split up into HU+ (12/19) and HU− (7/19) subgroups, respectively receiving or not a concomitant HU treatment. The principal outcomes measured were differences in the immunophenotyping between SCD patients and controls through chi-squared tests, t-tests, and Pearson’s correlation analysis between clinical and immunological parameters. Leukocyte and neutrophil increase, T-cell depletion with prevalence of memory T-cell compartment, NK and B-naïve subset elevation with memory and CD21low B subset reduction, and IgG expansion, significantly distinguished the SCD HU− subgroup from controls, with naïve T cells, switched-memory B cells and IgG maintaining differences between the SCD HU+ group and controls (p-value of <0.05). The mean CD4+ central-memory T-cell% count was the single independent variable showing a positive correlation with vaso-occlusive crisis score in the SCD group (Pearson’s R = 0.039). We report preliminary data assessing plausible clinical implications of baseline and HU-related SCD immunophenotypical alterations, which need to be validated in larger samples, but potentially affecting hypo-/a-splenism immuno-chemoprophylactic recommendations. Full article

(This article belongs to the Special Issue Acute and Chronic Sickle Cell Disease: Causes, Consequences, and Treatment)

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16 pages, 2362 KiB

Open AccessArticle

Isolation and Characterisation of Quercitrin as a Potent Anti-Sickle Cell Anaemia Agent from Alchornea cordifolia

by Olayemi Adeniyi, Rafael Baptista, Sumana Bhowmick, Alan Cookson, Robert J. Nash, Ana Winters, Jianying Shen and Luis A. J. Mur

J. Clin. Med. 2022, 11(8), 2177; https://doi.org/10.3390/jcm11082177 - 13 Apr 2022

Cited by 5 | Viewed by 3017

Abstract

Alchornea cordifolia Müll. Arg. (commonly known as Christmas Bush) has been used traditionally in Africa to treat sickle cell anaemia (a recessive disease, arising from the S haemoglobin (Hb) allele), but the active compounds are yet to be identified. Herein, we describe the [...] Read more.

Alchornea cordifolia Müll. Arg. (commonly known as Christmas Bush) has been used traditionally in Africa to treat sickle cell anaemia (a recessive disease, arising from the S haemoglobin (Hb) allele), but the active compounds are yet to be identified. Herein, we describe the use of sequential fractionation coupled with in vitro anti-sickling assays to purify the active component. Sickling was induced in HbSS genotype blood samples using sodium metabisulphite (Na₂S₂O₅) or through incubation in 100% N₂. Methanol extracts of A. cordifolia leaves and its sub-fractions showed >70% suppression of HbSS erythrocyte sickling. The purified compound demonstrated a 87.2 ± 2.39% significant anti-sickling activity and 93.1 ± 2.69% erythrocyte sickling-inhibition at 0.4 mg/mL. Nuclear magnetic resonance (NMR) spectra and high-resolution mass spectroscopy identified it as quercitrin (quercetin 3-rhamnoside). Purified quercitrin also inhibited the polymerisation of isolated HbS and stabilized sickle erythrocytes membranes. Metabolomic comparisons of blood samples using flow-infusion electrospray-high resolution mass spectrometry indicated that quercitrin could convert HbSS erythrocyte metabolomes to be like HbAA. Sickling was associated with changes in antioxidants, anaerobic bioenergy, and arachidonic acid metabolism, all of which were reversed by quercitrin. The findings described could inform efforts directed to the development of an anti-sickling drug or quality control assessments of A. cordifolia preparations. Full article

(This article belongs to the Special Issue Acute and Chronic Sickle Cell Disease: Causes, Consequences, and Treatment)

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14 pages, 2858 KiB

Open AccessArticle

Circulating Small Extracellular Vesicles May Contribute to Vaso-Occlusive Crises in Sickle Cell Disease

by Joanna Gemel, Jared Zhang, Yifan Mao, Gabrielle Lapping-Carr and Eric C. Beyer

J. Clin. Med. 2022, 11(3), 816; https://doi.org/10.3390/jcm11030816 - 03 Feb 2022

Cited by 2 | Viewed by 1506

Abstract

We previously found that the plasma of patients with sickle cell disease (SCD) contains large numbers of small extracellular vesicles (EVs) and that the EVs disrupt the integrity of endothelial cell monolayers (especially if obtained during episodes of acute chest syndrome, ACS). The [...] Read more.

We previously found that the plasma of patients with sickle cell disease (SCD) contains large numbers of small extracellular vesicles (EVs) and that the EVs disrupt the integrity of endothelial cell monolayers (especially if obtained during episodes of acute chest syndrome, ACS). The present study was designed to test the generality of this finding to other complications of SCD, specifically to evaluate the possibility that circulating EVs isolated during a vaso-occlusive crises (VOC) also cause damage to the intercellular connections between endothelial cells. Plasma was obtained from nine pediatric subjects at baseline and during VOC episodes. EVs isolated from these samples were added to cultures of microvascular endothelial cells. Immunofluorescence microscopy was employed to assess monolayer integrity and to localize two intercellular junction proteins (VE-cadherin and connexin43). The EVs isolated during VOC caused significantly greater monolayer disruption than those isolated at baseline. The extent of disruption varied between different episodes of VOC or ACS in the same patient. The VOC EVs disrupted the integrity of both junction proteins at appositional membranes. These results suggest that circulating EVs may be involved in modulating endothelial integrity contributing to the pathogenesis of different complications of SCD. Full article

(This article belongs to the Special Issue Acute and Chronic Sickle Cell Disease: Causes, Consequences, and Treatment)

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15 pages, 2502 KiB

Open AccessArticle

Plasma-Derived Hemopexin as a Candidate Therapeutic Agent for Acute Vaso-Occlusion in Sickle Cell Disease: Preclinical Evidence

by Thomas Gentinetta, John D. Belcher, Valérie Brügger-Verdon, Jacqueline Adam, Tanja Ruthsatz, Joseph Bain, Daniel Schu, Lisa Ventrici, Monika Edler, Hadi Lioe, Kalpeshkumar Patel, Chunsheng Chen, Julia Nguyen, Fuad Abdulla, Ping Zhang, Andreas Wassmer, Meena Jain, Marcel Mischnik, Matthias Pelzing, Kirstee Martin, Roslyn Davis, Svetlana Didichenko, Alexander Schaub, Nathan Brinkman, Eva Herzog, Adrian Zürcher, Gregory M. Vercellotti, Gregory J. Kato and Gerald Höbarth Show full author list Hide full author list

J. Clin. Med. 2022, 11(3), 630; https://doi.org/10.3390/jcm11030630 - 26 Jan 2022

Cited by 15 | Viewed by 5072

Abstract

People living with sickle cell disease (SCD) face intermittent acute pain episodes due to vaso-occlusion primarily treated palliatively with opioids. Hemolysis of sickle erythrocytes promotes release of heme, which activates inflammatory cell adhesion proteins on endothelial cells and circulating cells, promoting vaso-occlusion. In [...] Read more.

People living with sickle cell disease (SCD) face intermittent acute pain episodes due to vaso-occlusion primarily treated palliatively with opioids. Hemolysis of sickle erythrocytes promotes release of heme, which activates inflammatory cell adhesion proteins on endothelial cells and circulating cells, promoting vaso-occlusion. In this study, plasma-derived hemopexin inhibited heme-mediated cellular externalization of P-selectin and von Willebrand factor, and expression of IL-8, VCAM-1, and heme oxygenase-1 in cultured endothelial cells in a dose-responsive manner. In the Townes SCD mouse model, intravenous injection of free hemoglobin induced vascular stasis (vaso-occlusion) in nearly 40% of subcutaneous blood vessels visualized in a dorsal skin-fold chamber. Hemopexin administered intravenously prevented or relieved stasis in a dose-dependent manner. Hemopexin showed parallel activity in relieving vascular stasis induced by hypoxia-reoxygenation. Repeated IV administration of hemopexin was well tolerated in rats and non-human primates with no adverse findings that could be attributed to human hemopexin. Hemopexin had a half-life in wild-type mice, rats, and non-human primates of 80–102 h, whereas a reduced half-life of hemopexin in Townes SCD mice was observed due to ongoing hemolysis. These data have led to a Phase 1 clinical trial of hemopexin in adults with SCD, which is currently ongoing. Full article

(This article belongs to the Special Issue Acute and Chronic Sickle Cell Disease: Causes, Consequences, and Treatment)

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12 pages, 8861 KiB

Open AccessArticle

Benefits of a Disease Management Program for Sickle Cell Disease in Germany 2011–2019: The Increased Use of Hydroxyurea Correlates with a Reduced Frequency of Acute Chest Syndrome

by Joachim B. Kunz, Andreas Schlotmann, Andrea Daubenbüchel, Stephan Lobitz, Andrea Jarisch, Regine Grosse, Holger Cario, Lena Oevermann, Dani Hakimeh, Laura Tagliaferri and Andreas E. Kulozik

J. Clin. Med. 2021, 10(19), 4543; https://doi.org/10.3390/jcm10194543 - 30 Sep 2021

Cited by 3 | Viewed by 2130

Abstract

Sickle Cell Disease (SCD) is the most common monogenic disorder globally but qualifies as a rare disease in Germany. In 2012, the German Society for Paediatric Oncology and Haematology (GPOH) mandated a consortium of five university hospitals to develop a disease management program [...] Read more.

Sickle Cell Disease (SCD) is the most common monogenic disorder globally but qualifies as a rare disease in Germany. In 2012, the German Society for Paediatric Oncology and Haematology (GPOH) mandated a consortium of five university hospitals to develop a disease management program for patients with SCD. Besides other activities, this consortium issued treatment guidelines for SCD that strongly favour the use of hydroxyurea and propagated these guidelines in physician and patient education events. In order to quantify the effect of these recommendations, we made use of claims data that were collected by the research institute (WIdO) of the major German insurance company, the Allgemeine Ortskrankenkasse (AOK), and of publicly accessible data collected by the Federal Statistical Office (Statistisches Bundesamt, Destatis). While the number of patients with SCD in Germany increased from approximately 2200 in 2011 to approximately 3200 in 2019, important components of the recently issued treatment guidelines have been largely implemented. Specifically, the use of hydroxyurea has more than doubled, resulting in a proportion of approximately 44% of all patients with SCD being treated with hydroxyurea in 2019. In strong negative correlation with the use of hydroxyurea, the frequency of acute chest syndromes decreased. Similarly, the proportion of patients who required analgesics and hospitals admissions declined. In sum, these data demonstrate an association between the dissemination of treatment guidelines and changes in clinical practice. The close temporal relationship between the increased use of hydroxyurea and the reduction in the incidence of acute chest syndrome in a representative population-based analysis implies that these changes in clinical practice contributed to an improvement in key measures of disease activity. Full article

(This article belongs to the Special Issue Acute and Chronic Sickle Cell Disease: Causes, Consequences, and Treatment)

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