title: Disturbance of plasma and platelet thrombospondin levels in sickle cell disease.
abstract: Thrombospondin (TSP), a large protein found in platelet alpha-granules (as TSP-1), mediates adhesion of sickle reticulocytes to cultured vascular endothelium. To further explore the physiologic relevance of this observation, we have measured plasma TSP levels and platelet TSP-1 content in subjects with sickle cell disease. Plasma TSP levels were similar for normal controls (mean 491 ng/ml, range 331-723) and steady-state HbSS patients (mean 536, range 333-1107) and were significantly (P = 0.012) but variably elevated for HbSS patients presenting with acute painful crisis (mean 868, range 442-2780). Some of these elevated plasma TSP levels reached those previously observed to support maximal red cell adhesion to endothelium in vitro. Compared to normals, both steady-state and in-crisis HbSS patients had significantly (P < 0.001) depressed platelet TSP-1 content (82.6 +/- 11.9, 47.1 +/- 16.0 and 45.9 +/- 20.7 ng/l0(6) platelets, respectively, mean +/- SD). HbSC disease patients, all examined during steady state, had low-normal plasma levels of TSP and either normal or depressed platelet TSP-1 content. Serial observations on three sickle cell anemia subjects indicated a probable relationship between platelet TSP-1 release, elevated plasma TSP levels, and acute vaso-occlusive episodes. These results suggest a state of ongoing release and depletion of TSP-1 from activated platelets in patients with sickle cell disease.
authors.affiliation: Department of Medicine, University of Minnesota Medical School, Minneapolis, 55455, USA.
authors.forename: P V
authors.initials: PV
authors.lastname: Browne
authors.forename: D F
authors.initials: DF
authors.lastname: Mosher
authors.forename: M H
authors.initials: MH
authors.lastname: Steinberg
authors.forename: R P
authors.initials: RP
authors.lastname: Hebbel
mesh_terms: D000208:Acute Disease; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000503:physiopathology; D001792:Blood Platelets / Q000737:chemistry*; D006450:Hemoglobin SC Disease / Q000097:blood* / Q000503:physiopathology; D006801:Humans; D008562:Membrane Glycoproteins / Q000097:blood*; D010146:Pain / Q000097:blood / Q000503:physiopathology; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D013154:Spleen / Q000503:physiopathology; D019699:Thrombospondins
chemical_list: D008562:Membrane Glycoproteins; D019699:Thrombospondins