title: Microvesicles in haemoglobinopathies offer insights into mechanisms of hypercoagulability, haemolysis and the effects of therapy.
abstract: Levels of circulating red blood cell (RBC)-derived vesicles are increased in sickle cell anaemia (SCA) and thalassaemia intermedia (TI) but the mechanisms, effects and controlling factors may differ. This study found that levels of vesicles and intravascular haemolysis were linked as shown by the correlation between levels of vesicles and plasma Hb. Vesicle levels were 6-fold greater in SCA and 4-fold greater in TI than in controls. The proportion of plasma Hb within vesicles was increased in SCA and TI with a significantly higher proportion in TI. We examined whether subpopulations of RBC expressing phosphatidylserine (PS) were a source of PS(+) vesicles and observed a significant association. Thrombin generation was promoted by the vesicles in which 40-50% expressed PS. In TI, markers of thrombin generation were significantly related to PS(+) RBC. Splenectomy in TI had significant effects including greater increases in vesicle levels, plasma Hb, PS(+) RBCs and thrombin generation markers than in unsplenectomised patients. In hydroxycarbamide (HC)-treated SCA patients these measures were decreased compared with untreated controls. The relationship between vesicle levels and plasma Hb suggests a mechanism linking vesiculation to haemolysis and consequently nitric oxide (NO) bioavailability and suggests a means by which HC treatment improves NO bioavailability.
authors.affiliation: Department of Medicine, Mt Sinai Hospital, Chicago, IL 60608, USA. wesm@sinai.org
authors.forename: Maxwell
authors.initials: M
authors.lastname: Westerman
authors.forename: Arnold
authors.initials: A
authors.lastname: Pizzey
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Hirschman
authors.forename: Mario
authors.initials: M
authors.lastname: Cerino
authors.forename: Yonit
authors.initials: Y
authors.lastname: Weil-Weiner
authors.forename: Prya
authors.initials: P
authors.lastname: Ramotar
authors.forename: Ada
authors.initials: A
authors.lastname: Eze
authors.forename: Andrew
authors.initials: A
authors.lastname: Lawrie
authors.forename: Gordon
authors.initials: G
authors.lastname: Purdy
authors.forename: Ian
authors.initials: I
authors.lastname: Mackie
authors.forename: John
authors.initials: J
authors.lastname: Porter
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000473:pathology; D004910:Erythrocyte Membrane / Q000473:pathology; D004913:Erythrocytes, Abnormal / Q000473:pathology*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013156:Splenectomy; D013917:Thrombin / Q000096:biosynthesis; D019851:Thrombophilia / Q000097:blood / Q000209:etiology* / Q000473:pathology; D055815:Young Adult; D017086:beta-Thalassemia / Q000097:blood* / Q000473:pathology
chemical_list: D006454:Hemoglobins; D013917:Thrombin