The spleen and sickle cell disease: the sick(led) spleen

Brousse, Valentine; Buffet, Pierre; Rees, David C.

doi:10.1111/bjh.12950

Cited by 231 publications

(251 citation statements)

References 76 publications

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“…10,11 Hyposplenism is present in the majority of SCD patients before 12 months of age. 20 An increased number of PS-exposed red cells has also been observed by flow cytometry in circulating red cells after splenectomy. 21 We analyzed red cells from two splenectomized but otherwise healthy individuals.…”

mentioning

confidence: 87%

Autophagic vesicles on mature human reticulocytes explain phosphatidylserine-positive red cells in sickle cell disease

Mankelow

Griffiths

Trompeter

et al. 2015

Blood

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Key Points• Reticulocyte maturation involves the release of intact, inside-out autophagic vesicles with PS exposed on their surface.• Elevated levels of autophagic vesicles on circulating reticulocytes cause PS exposure in patients with SCD.During maturation to an erythrocyte, a reticulocyte must eliminate any residual organelles and reduce its surface area and volume. Here we show this involves a novel process whereby large, intact, inside-out phosphatidylserine (PS)-exposed autophagic vesicles are extruded. Cell surface PS is a well-characterized apoptotic signal initiating phagocytosis. In peripheral blood from patients after splenectomy or in patients with sickle cell disease (SCD), the number of circulating red cells exposing PS on their surface is elevated. We show that in these patients PS is present on the cell surface of red cells in large (∼1.4 mm) discrete areas corresponding to autophagic vesicles. The autophagic vesicles found on reticulocytes are identical to those observed on red cells from splenectomized individuals and patients with SCD. Our data suggest the increased thrombotic risk associated with splenectomy, and patients with hemoglobinopathies is a possible consequence of increased levels of circulating mature reticulocytes expressing inside-out PS-exposed autophagic vesicles because of asplenia. (Blood. 2015;126(15):1831-1834) IntroductionThe erythrocyte is one of the most abundant, accessible, and best characterized of human cells but until the recent development of in vitro erythroid culture systems 1,2 obtaining large numbers of its precursor cell, the human reticulocyte has been problematic. Reticulocytes are broadly grouped into R1, motile multilobular, and normally confined to bone marrow, and R2, which are nonmotile, much more mechanically stable, and released into peripheral circulation where they comprise ;2% of red blood cells.3,4 During maturation to an erythrocyte, the reticulocyte must lose ;20% of its surface area, reduce its volume, and degrade or eliminate residual cytosolic organelles. Current dogma considers that loss of plasma membrane is through the release of endocytosed plasma membrane as exosomes, whereas purging of cellular organelles is executed by autophagy. 5Surface phosphatidylserine (PS) exposure is a well characterized signal for initiating phagocytosis of unwanted cells or cellular material. 6PS is normally located on the intracellular surface of plasma membranes. Relocation to the extracellular surface may occur by activation of a scramblase 7 or a bidirectional trafficking process involving cytosolic vesicles.8 PS-exposed red cells are found in the peripheral blood of patients who have undergone splenectomy, or have sickle cell disease (SCD) or thalassemia. 9-13 Study designFor details of anonymized patient samples, antibodies used, and full methods, see supplemental Methods, available on the Blood Web site. Briefly, reticulocytes were derived from erythroid cultures and confocal microscopy was performed as described.2 PS was detected using Annexin V fluore...

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mentioning

confidence: 87%

Autophagic vesicles on mature human reticulocytes explain phosphatidylserine-positive red cells in sickle cell disease

Mankelow

Griffiths

Trompeter

et al. 2015

Blood

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“…Infection is probably the most important cause of premature deaths among these children. Splenic dysfunction has a key role in the increased susceptibility to bacterial infections seen in children with sickle cell disease, 83 and pneumococcal and haemophilus infections seem to be important both in the northern and southern hemispheres, suggesting that basic interventions, including penicillin prophylaxis and vaccinations, could lead to substantial improvement in survival among patients with sickle cell disease in lower-income countries, just as such interventions have done in high-income countries. 84 Malaria is the other infection that is widely believed to contribute to excess mortality among patients with sickle cell disease in Africa, although data supporting this belief are scant.…”

Section: Infectious Diseasesmentioning

confidence: 99%

Sickle Cell Disease

2017

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“…However, 60% of the children who underwent laparoscopic splenectomies in the present study were under five years old, which is the most common age for an acute splenic sequestration crisis. 10 As sequestration is rare beyond this age, it seems likely that some patients required a splenectomy for some other reason.…”

Section: Discussionmentioning

confidence: 99%

“…9 Paediatric SCD patients may require a splenectomy for various indications, such as recurrent splenic sequestration or splenic dysfunction. 10 The effectiveness of splenectomies in improving haematological outcomes is well-established. 11,12 However, most studies in the medical literature combine the results of laparo-scopic splenectomies carried out for various indications such as hereditary spherocytosis, idiopathic thrombocytopaenic purpura or chronic myelomonocytic leukaemia, with only a small number focusing solely on laparoscopic splenectomies among patients with SCD.…”

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confidence: 99%

Laparoscopic Splenectomy Alone for Sickle Cell Disease: Account of 50 paediatric cases

Al-Balushi

Bhatti

Ehsan

et al. 2016

SQUMJ

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Objectives: In Oman, the most frequent indication for a splenectomy in children is sickle cell disease (SCD), which is one of the most common haematological disorders in the Gulf region. This study aimed to describe paediatric laparoscopic splenectomies alone for SCD at a tertiary hospital in Oman. Methods: This study was conducted between February 2010 and October 2015 at the Sultan Qaboos University Hospital, Muscat, Oman. The medical records of all children aged ≤15 years old undergoing splenectomies during the study period were reviewed. Results: A total of 71 children underwent laparoscopic splenectomies during the study period; of these, 50 children (28 male and 22 female) underwent laparoscopic splenectomies alone for SCD. The children's weight ranged between 11-43 kg. The most common indication for a splenectomy was a recurrent splenic sequestration crisis (92%). Surgically removed spleens weighed between 155-1,200 g and measured between 9-22 cm. Operative times ranged between 66-204 minutes and intraoperative blood loss ranged between 10-800 mL. One patient required conversion to an open splenectomy. Postoperative complications were noted in only four patients. The median hospital stay duration was three days. Conclusion: Among this cohort, the mean operating time was comparable to that reported in the international literature. In addition, rates of conversion and postoperative complications were very low. These findings indicate that a laparoscopic splenectomy alone in paediatric patients with SCD is a feasible option.

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The spleen and sickle cell disease: the sick(led) spleen

Cited by 231 publications

References 76 publications

Autophagic vesicles on mature human reticulocytes explain phosphatidylserine-positive red cells in sickle cell disease

Autophagic vesicles on mature human reticulocytes explain phosphatidylserine-positive red cells in sickle cell disease

Sickle Cell Disease

Laparoscopic Splenectomy Alone for Sickle Cell Disease: Account of 50 paediatric cases

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