DISTURBANCE OF PLASMA AND PLATELET THROMBOSPONDIN LEVELS IN SICKLE-CELL DISEASE

Thrombospondin (TSP), a large protein found in platelet alpha-granules (as TSP-1), mediates adhesion of sickle reticulocytes to cultured vas cular endothelium. To further explore the physiologic relevance of thi s observation, we have measured plasma TSP levels and platelet TSP-1 c ontent in subjects with sickle cell disease, Plasma TSP levels were si milar for normal controls (mean 491 ng/ml, range 331-723) and steady-s tate HbSS patients (mean 536, range 333-1107) and were significantly ( P = 0.012) but variably elevated for HbSS patients presenting with acu te painful crisis (mean 868, range 442-2780). Some of these elevated p lasma TSP levels reached those previously observed to support maximal red cell adhesion to endothelium in vitro, Compared to normals, both s teady-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/10(6) platelets, respectively, mean +/-SD). HbSC disease patients, all examined during steady state, had low-normal plasma lev els of TSP and either normal or depressed platelet TSP-1 content. Seri al observations on three sickle cell anemia subjects indicated a proba ble relationship between platelet TSP-1 release, elevated plasma TSP l evels, and acute vasoocclusive episodes, These results suggest a state of ongoing release and depletion of TSP-1 from activated platelets in patients with sickle cell disease. (C) 1996 Wiley-Liss, Inc.