Disturbance of plasma and platelet thrombospondin levels in sickle cell disease

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Abstract
Thrombospondin (TSP), a large protein found in platelet α‐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/109 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 vasoocclusive episodes. These results suggest a state of ongoing release and depletion of TSP‐1 from activated platelets in patients with sickle cell disease.