title: Vasculopathy, inflammation, and blood flow in leg ulcers of patients with sickle cell anemia.
abstract: Chronic leg ulcers are frequent and debilitating complications of sickle cell anemia. Inadequate blood supply has been postulated to be an important factor in their occurrence and delayed healing. Little is known about their microcirculatory and histopathological changes. We evaluated the microcirculation of lower extremity ulcers with laser speckle contrast imaging and infrared thermography and obtained clinical and laboratory characteristics in 18 adults with sickle cell anemia and chronic leg ulcers. Skin biopsies were obtained in four subjects. Subjects had markers of severe disease, anemia, high degree of hemolysis, inflammation, and thrombophilia. The highest blood flow was present in the ulcer bed, progressively less in the immediate periwound area, and an unaffected control skin area in the same extremity. Microscopic examination showed evidence of venostasis, inflammation, and vasculopathy. Blood vessels were increased in number, had activated endothelium and evidence of thrombosis/recanalization. High blood flow may be due to chronic inflammation, cutaneous vasodilatation, venostasis, and in situ thrombosis. These changes in skin microcirculation are similar to chronic venous ulcers in the non-sickle cell disease (SCD) population, thus suggesting that leg ulcers may be another end-organ complication with endothelial dysfunction that appears in patients with SCD at a younger age and with higher frequency than in the general population.
authors: Hematology Branch, NHLBI, National Institutes of Health, Bethesda, Maryland.
authors: Caterina P
authors: CP
authors: Minniti
authors: Kara-Marie H
authors: KM
authors: Delaney
authors: Alexander M
authors: AM
authors: Gorbach
authors: Dihua
authors: D
authors: Xu
authors: Chyi-Chia Richard
authors: CC
authors: Lee
authors: Nitin
authors: N
authors: Malik
authors: Antony
authors: A
authors: Koroulakis
authors: Matthew
authors: M
authors: Antalek
authors: Jordan
authors: J
authors: Maivelett
authors: Marlene
authors: M
authors: Peters-Lawrence
authors: Enrico M
authors: EM
authors: Novelli
authors: Sophie M
authors: SM
authors: Lanzkron
authors: Karen C
authors: KC
authors: Axelrod
authors: Gregory J
authors: GJ
authors: Kato
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications*; D001706:Biopsy; D005260:Female; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000473:pathology; D007871:Leg Ulcer / Q000175:diagnosis / Q000209:etiology* / Q000473:pathology*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D012039:Regional Blood Flow; D012307:Risk Factors; D012867:Skin / Q000098:blood supply*; D013817:Thermography
references: Br J Dermatol. 2008 Feb;158(2):339-44
references: 18047512
references: Hematol Oncol Clin North Am. 1996 Dec;10(6):1333-44
references: 8956020
references: Am J Hematol. 1991 Jun;37(2):133-4
references: 2069160
references: Microvasc Res. 2012 Nov;84(3):262-9
references: 22784510
references: Circ Cardiovasc Imaging. 2012 Jan;5(1):155-63
references: 22253335
references: Ann Intern Med. 1989 Sep 15;111(6):534-6
references: 2774375
references: Skin Res Technol. 2006 Nov;12(4):247-53
references: 17026655
references: Eur J Vasc Endovasc Surg. 2012 Mar;43(3):355-8
references: 22264424
references: Ann N Y Acad Sci. 2010 Aug;1202:214-20
references: 20712795
references: Ostomy Wound Manage. 2012 Jun;58(6):20-2, 24, 26-9
references: 22688856
references: N Engl J Med. 2004 Feb 26;350(9):886-95
references: 14985486
references: N Engl J Med. 2000 Jun 22;342(25):1855-65
references: 10861320
references: Annu Int Conf IEEE Eng Med Biol Soc. 2010;2010:1978-81
references: 21096787
references: Dermatologica. 1990;181(1):56-9
references: 2394305
references: N Engl J Med. 2011 Jul 7;365(1):44-53
references: 21732836
references: Am J Hematol. 2011 Aug;86(8):705-8
references: 21630312
references: Medicine (Baltimore). 2005 Nov;84(6):363-376
references: 16267411
references: Blood. 1990 Jun 15;75(12):2467-8
references: 2350585
references: Pediatr Dermatol. 2003 Sep-Oct;20(5):427-8
references: 14521562
references: Semin Respir Crit Care Med. 2009 Aug;30(4):421-8
references: 19634081
references: Blood. 2006 Mar 15;107(6):2279-85
references: 16291595
references: Br J Haematol. 2010 Dec;151(5):516-24
references: 20955402
references: Adv Skin Wound Care. 2004 Oct;17(8):410-6
references: 15492676
references: Circulation. 1984 Nov;70(5):806-11
references: 6488495
references: Angiogenesis. 2012 Mar;15(1):87-98
references: 22198198
references: N Engl J Med. 1999 Sep 2;341(10):738-46
references: 10471461
references: Br J Haematol. 2008 Jul;142(1):119-25
references: 18477043
references: J Lab Clin Med. 1970 Oct;76(4):632-40
references: 5458026
references: Am J Hematol. 2009 Sep;84(9):618-25
references: 19610078
references: Ann Plast Surg. 2010 Mar;64(3):351-4
references: 20179489
references: Ann Neurol. 1997 Nov;42(5):699-704
references: 9392568
references: Clin Sci (Lond). 2000 Jun;98(6):667-72
references: 10814603
references: Hematol Cell Ther. 1996 Jul;38(3):279-84
references: 8974793
references: Hemoglobin. 2013;37(4):325-32
references: 23600469
references: N Engl J Med. 1984 Dec 13;311(24):1534-8
references: 6504081
references: Clin Sci (Lond). 1997 Feb;92(2):153-8
references: 9059316
references: Am J Hematol. 2010 Oct;85(10):831-3
references: 20872960
references: Br J Haematol. 2001 Feb;112(2):527-9
references: 11167859
references: Blood. 2010 Jul 22;116(3):456-65
references: 20304807
references: Hematol Oncol Clin North Am. 2005 Oct;19(5):943-56, viii-ix
references: 16214654
references: Wound Repair Regen. 1996 Apr-Jun;4(2):240-3
references: 17177820