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The Clinical Epidemiology of Sickle Cell Disease, a Severe Multi-Organ Affection

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 30778

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Special Issue Editor

Prof. Dr. Mariane de Montalembert

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Guest Editor

1. Referral Center for Sickle Cell Disease, AP-HP Centre-Paris University, Paris, France
2. Department of General Pediatrics and Pediatric Infectious Diseases, Necker Hospital for Sick Children, Paris, France
3. Laboratory of Excellence GR-Ex, Paris, France
Interests: sickle cell disease; transfusion, allo-immunization; hydroxyurea; stroke; innate immunity; acute chest syndrome; liver disease

Special Issue Information

Dear colleagues,

Sickle cell disease (SCD) has shifted in high-income countries from fatal illness in children to chronic disease with multiple organ dysfunctions in adults. Median life expectancy has increased up to 50 years, though median age of death has remained steady at 37 years, with fatal issues occurring mostly in patients with preexisting organ failures, such as kidney injury, cerebral vasculopathy, and pulmonary hypertension. All organs can be affected by SCD via variable mechanisms including heme-related vascular damage, ischemia-reperfusion injury, inflammation, and neoangiogenesis. Organ dysfunctions may settle as soon as childhood but are often long asymptomatic and require systematic screening for being diagnosed. Evidencing early organ damage is a new challenge of the management of SCD. It will allow individual prediction of the disease severity, and, perhaps, tailored management.

Current therapeutic strategies must be improved. Most patients still experience excruciating pain crises, requiring the development of new strategies. Given the major role of transfusion, prevention and treatment of delayed hemolytic transfusion reaction are among priorities. Access to hydroxyurea must be improved. Effectiveness of new licensed drugs such as L-Glutamine, Voxelotor, and Crizanluzimab in preventing or improving organ damage remains to be studied. Debating indications of HSCT with alternative donors and gene therapy in SCD will be one of our most difficult scientific and ethical questions. Patients must be well informed about the debates on the risk/benefit ratio of these options and define their priorities. Lastly, management of SCD in low-income countries remains one of the main challenges.

Prof. Dr. Mariane de Montalembert
Guest Editor

Manuscript Submission Information

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Keywords

Epidemiology
Transfusion
Pain
Kidney failure
Stroke
Silent cerebral infarct
osteonecrosis
Organ dysfunctions
Prediction of severity

Published Papers (7 papers)

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Research

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13 pages, 2304 KiB

Open AccessArticle

Automated Red Cell Exchange in the Management of Sickle Cell Disease

by Dimitris A. Tsitsikas, Saket Badle, Rhys Hall, John Meenan, Oloruntoyin Bello-Sanyaolu, Funmilayo Orebayo, Jibril Abukar, Mohamed Elmi, Afsana Mulla, Shalini Dave, Natasha Lewis, Manisha Sharma, Basabi Chatterjee and Roger J. Amos

J. Clin. Med. 2021, 10(4), 767; https://doi.org/10.3390/jcm10040767 - 15 Feb 2021

Cited by 6 | Viewed by 2630

Abstract

Red cell transfusion represents one of the cornerstones of the chronic management of sickle cell disease, as well as its acute complications. Automated red cell exchange can rapidly lower the number of circulating sickle erythrocytes, without causing iron overload. Here, we describe our experience, having offered this intervention since 2011. A transient reduction in the platelet count by 61% was observed after the procedure. This was not associated with any haemorrhagic complications. Despite exposure to large volumes of blood, the alloimmunisation rate was only 0.027/100 units of red cells. The absence of any iron loading was confirmed by serial Ferriscans, performed over a number of years. However, patients with advanced chronic kidney disease showed evidence of iron loading due to reduced innate haemopoiesis and were subsequently switched to simple transfusions. A total of 59% of patients were on regular automated red cell exchange with a history of recurrent painful crises. A total of 77% responded clinically, as evidenced by at least a 25% reduction in their emergency hospital attendance for pain management. The clinical response was gradual and increased the longer patients stayed on the program. The earliest sign of clinical response was a reduction in the length of stay when these patients were hospitalised, indicating that a reduction in the severity of crises precedes the reduction in their frequency. Automated red cell exchange also appeared to be beneficial for patients with recurrent leg ulcers and severe, drug resistant stuttering priapism, while patients with pulmonary hypertension showed a dramatic improvement in their symptoms as well as echocardiographic parameters. Full article

(This article belongs to the Special Issue The Clinical Epidemiology of Sickle Cell Disease, a Severe Multi-Organ Affection)

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10 pages, 1064 KiB

Open AccessArticle

Procalcitonin to Reduce Antibiotic Exposure during Acute Chest Syndrome in Adult Patients with Sickle-Cell Disease

by Keyvan Razazi, Ségolène Gendreau, Elise Cuquemelle, Mehdi Khellaf, Constance Guillaud, Bertrand Godeau, Giovanna Melica, Stéphane Moutereau, Camille Gomart, Slim Fourati, Nicolas De Prost, Guillaume Carteaux, Christian Brun-Buisson, Pablo Bartolucci, Anoosha Habibi and Armand Mekontso Dessap

J. Clin. Med. 2020, 9(11), 3718; https://doi.org/10.3390/jcm9113718 - 19 Nov 2020

Cited by 6 | Viewed by 1982

Abstract

Acute chest syndrome (ACS) is a major complication of sickle-cell disease. Bacterial infection is one cause of ACS, so current guidelines recommend the routine use of antibiotics. We performed a prospective before–after study in medical wards and an intensive-care unit (ICU). During the control phase, clinicians were blinded to procalcitonin concentration results. We built an algorithm using the obtained measurements to hasten antibiotic cessation after three days of treatment if bacterial infection was not documented, and procalcitonin concentrations were all <0.5 μg/L. During the intervention period, the procalcitonin algorithm was suggested to physicians as a guide for antibiotic therapy. The primary endpoint was the number of days alive without antibiotics at Day 21. One-hundred patients were analyzed (103 ACS episodes, 60 in intervention phase). Possible or proven lung infection was diagnosed during 13% of all ACS episodes. The number of days alive without antibiotics at Day 21 was higher during the intervention phase: 15 [14–18] vs. 13 [13,14] days (p = 0.001). More patients had a short (≤3 days) antibiotic course during intervention phase: 31% vs 9% (p = 0.01). There was neither infection relapse nor pulmonary superinfection in the entire cohort. A procalcitonin-guided strategy to prescribe antibiotics in patients with ACS may reduce antibiotic exposure with no apparent adverse outcomes. Full article

(This article belongs to the Special Issue The Clinical Epidemiology of Sickle Cell Disease, a Severe Multi-Organ Affection)

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12 pages, 687 KiB

Open AccessArticle

Fat Embolism Syndrome in Sickle Cell Disease

by Dimitris A. Tsitsikas, Jessica Bristowe and Jibril Abukar

J. Clin. Med. 2020, 9(11), 3601; https://doi.org/10.3390/jcm9113601 - 8 Nov 2020

Cited by 32 | Viewed by 4585

Abstract

Fat embolism syndrome is a devastating complication of sickle cell disease resulting from extensive bone marrow necrosis and associated with high mortality rates, while survivors often suffer severe neurological sequelae. Despite that, the syndrome remains under-recognised and under-diagnosed. Paradoxically, it affects exclusively patients with mild forms of sickle cell disease, predominantly HbSC and HbSβ⁺. A significant number of cases occur in the context of human parvovirus B19 infection. We provide here a brief summary of the existing literature and describe our experience treating 8 patients in our institution. One patient had HbSS, 6 HbSC and 1 HbSβ⁺. All patients developed type I respiratory failure and neurological involvement either at presentation or within the first 72 h. The most striking laboratory abnormality was a 100-fold increase of the serum ferritin from baseline. Seven patients received emergency red cell exchange and 1 simple transfusion. Two patients (25%) died, 2 patients (25%) suffered severe neurological impairment and 1 (12%) mild neurological impairment on discharge, while 3 (38%) patients made a complete recovery. With long-term follow-up, 1 patient with severe neurological impairment and one patient with mild neurological impairment made dramatic improvements, making the long-term complete recovery or near complete recovery rate 63%. Immediate red cell exchange transfusion can be lifesaving and should be instituted as soon as the syndrome is suspected. However, as the outcomes remain unsatisfactory despite the increasing use of red cell exchange, we suggest additional therapeutic measures such as therapeutic plasma exchange and pre-emptive transfusion for high risk patients. Full article

(This article belongs to the Special Issue The Clinical Epidemiology of Sickle Cell Disease, a Severe Multi-Organ Affection)

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Review

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22 pages, 1889 KiB

Open AccessReview

Epidemiology of Stroke in Sickle Cell Disease

by Fenella Jane Kirkham and Ikeoluwa A. Lagunju

J. Clin. Med. 2021, 10(18), 4232; https://doi.org/10.3390/jcm10184232 - 18 Sep 2021

Cited by 26 | Viewed by 5251

Abstract

Sickle cell disease is the most common cause of stroke in childhood, both ischaemic and haemorrhagic, and it also affects adults with the condition. Without any screening or preventative treatment, the incidence appears to fall within the range 0.5 to 0.9 per 100 patient years of observation. Newborn screening with Penicillin prophylaxis and vaccination leading to reduced bacterial infection may have reduced the incidence, alongside increasing hydroxyurea prescription. Transcranial Doppler screening and prophylactic chronic transfusion for at least an initial year has reduced the incidence of stroke by up to 10-fold in children with time averaged mean of the maximum velocity >200 cm/s. Hydroxyurea also appears to reduce the incidence of first stroke to a similar extent in the same group but the optimal dose remains controversial. The prevention of haemorrhagic stroke at all ages and ischaemic stroke in adults has not yet received the same degree of attention. Although there are fewer studies, silent cerebral infarction on magnetic resonance imaging (MRI), and other neurological conditions, including headache, epilepsy and cognitive dysfunction, are also more prevalent in sickle cell disease compared with age matched controls. Clinical, neuropsychological and quantitative MRI screening may prove useful for understanding epidemiology and aetiology. Full article

(This article belongs to the Special Issue The Clinical Epidemiology of Sickle Cell Disease, a Severe Multi-Organ Affection)

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16 pages, 2253 KiB

Open AccessReview

Opioids and Sickle Cell Disease: From Opium to the Opioid Epidemic

by Samir K. Ballas

J. Clin. Med. 2021, 10(3), 438; https://doi.org/10.3390/jcm10030438 - 23 Jan 2021

Cited by 9 | Viewed by 3803

Abstract

Sickle cell disease (SCD) is an inherited disorder of hemoglobin structure. The clinical effects of the sickle gene are pleiotropic in nature causing multiple phenotypic expressions associated with the various complications of the disease. The hallmark of the disease is pain that could be acute, chronic, nociceptive, or neuropathic that could occur singly or in various combinations. The acute vaso-occlusive painful crisis (VOC) is the most common cause of admissions to the Emergency Department and/or the hospital. Although progress has been made in understanding the pathophysiology of SCD as well as in developing preventive and curative therapies, effective pain management continues to lag behind and depend mostly on the use of opioids. This review describes the history of opioids from the ancient times of opium to the current use of the many controversial opioids. In addition, the major cause of death of patients with SCD is the complications of the disease itself and not the use of opioids. The use of opioids by patients with SCD has been stable over the years. Judicious use of opioids to treat sickle cell pain according to available guidelines could minimize the unnecessary suffering experienced by patients with SCD. Full article

(This article belongs to the Special Issue The Clinical Epidemiology of Sickle Cell Disease, a Severe Multi-Organ Affection)

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20 pages, 795 KiB

Open AccessReview

Considerations for Cannabis Use to Treat Pain in Sickle Cell Disease

by Donovan A. Argueta, Anupam Aich, Fjolla Muqolli, Hemanth Cherukury, Varun Sagi, Nicholas V. DiPatrizio and Kalpna Gupta

J. Clin. Med. 2020, 9(12), 3902; https://doi.org/10.3390/jcm9123902 - 1 Dec 2020

Cited by 5 | Viewed by 4797

Abstract

Pain in Sickle Cell Disease (SCD) is a major comorbidity and unique with acute pain due to recurrent and episodic vaso-occlusive crises as well as chronic pain, which can span an individual’s entire life. Opioids are the mainstay treatment for pain in SCD. Due to recent health crises raised by adverse effects including deaths from opioid use, pain management in SCD is adversely affected. Cannabis and its products are most widely used for pain in multiple conditions and also by patients with SCD on their own. With the availability of “Medical Cannabis” and approval to use cannabis as medicine across majority of States in the United States as well as over-the-counter preparations, cannabis products are being used increasingly for SCD. The reliability of many of these products remains questionable, which poses a major health risk to the vulnerable individuals seeking pain relief. Therefore, this review provides up to date insights into available categories of cannabis-based treatment strategies, their mechanism of action and pre-clinical and clinical outcomes in SCD. It provides evidence for the benefits and risks of cannabis use in SCD and cautions about the unreliable and unvalidated products that may be adulterated with life-threatening non-cannabis compounds. Full article

(This article belongs to the Special Issue The Clinical Epidemiology of Sickle Cell Disease, a Severe Multi-Organ Affection)

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10 pages, 398 KiB

Open AccessFeature PaperReview

Fetal Hemoglobin in Sickle Hemoglobinopathies: High HbF Genotypes and Phenotypes

by Martin H. Steinberg

J. Clin. Med. 2020, 9(11), 3782; https://doi.org/10.3390/jcm9113782 - 23 Nov 2020

Cited by 28 | Viewed by 6984

Abstract

Fetal hemoglobin (HbF) usually consists of 4 to 10% of total hemoglobin in adults of African descent with sickle cell anemia. Rarely, their HbF levels reach more than 30%. High HbF levels are sometimes a result of β-globin gene deletions or point mutations in the promoters of the HbF genes. Collectively, the phenotype caused by these mutations is called hereditary persistence of fetal hemoglobin, or HPFH. The pancellularity of HbF associated with these mutations inhibits sickle hemoglobin polymerization in most sickle erythrocytes so that these patients usually have inconsequential hemolysis and few, if any, vasoocclusive complications. Unusually high HbF can also be associated with variants of the major repressors of the HbF genes, BCL11A and MYB. Perhaps most often, we lack an explanation for very high HbF levels in sickle cell anemia. Full article

(This article belongs to the Special Issue The Clinical Epidemiology of Sickle Cell Disease, a Severe Multi-Organ Affection)

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