Abstract
Experimental thrombocytopenia results in endothelial alterations associated with bleeding. In this study prednisone was shown to prevent or reverse these changes, which supports the clinical inference that adrenocorticosteroids decrease capillary fragility in thrombocytopenia. Rabbits (3-4 kg), intraperitoneally injected with busulfan, developed 98-99% reductions in platelet count and hemorrhaged profusely. Orally administered prednisone (0.2 mg/kg or 1.0 mg/kg daily) reduced bleeding despite persistent thrombocytopenia. Tongue biopsies obtained after 3 days of prednisone treatment were examined by electron microscopy. Normal rabbits served as controls. 25 consecutive capillaries or venules from each of four animals in the control group and each of five experimental groups were examined for fenestrations, “thin spots” (<800 A thick), and mean wall thickness as determined by planimetry. Vessels from control animals had no thin spots or fenestrations, and the mean vessel wall thickness was 4,254±105 A SEM. The 100 vessels from the thrombocytopenic animals had a mean vessel wall thickness of 2,081±218 A (P < 0.001), and 42 had thin spots of fenestrations. After administration of the smaller dosage of prednisone, the mean vessel wall thickness increased to 3,556±40 A (P < 0.001), and only nine vessels had thin spots or fenestrations. With the larger dosage, only six vessels had thin spots or fenestrations and the mean vessel wall thickness of this group increased to 3,704±206 A (P < 0.005). All preparations demonstrated normal endothelial junctions. The data are consistent with the hypothesis that the bleeding of thrombocytopenia is caused by altered capillary and venule endothelium and that diminished bleeding observed with prednisone administration results from amelioration of these endothelial changes.
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- Bruns R. R., Palade G. E. Studies on blood capillaries. II. Transport of ferritin molecules across the wall of muscle capillaries. J Cell Biol. 1968 May;37(2):277–299. doi: 10.1083/jcb.37.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bull B. S., Schneiderman M. A., Brecher G. Platelet counts with the Coulter counter. Am J Clin Pathol. 1965 Dec;44(6):678–688. doi: 10.1093/ajcp/44.6.678. [DOI] [PubMed] [Google Scholar]
- Evensen S. A., Jeremic M., Hjort P. F. Experimental thrombocytopenia induced by Busulphan (Myleran) in rabbits: extremely low platelet levels and intact plasma clotting system. Thromb Diath Haemorrh. 1968 Jul 31;19(3):570–577. [PubMed] [Google Scholar]
- FALOON W. W., GREENE R. W., LOZNER E. L. The hemostatic defect in thrombocytopenia as studied by the use of ACTH and cortisone. Am J Med. 1952 Jul;13(1):12–20. doi: 10.1016/0002-9343(52)90076-4. [DOI] [PubMed] [Google Scholar]
- Gore I., Takada M., Austin J. Ultrastructural basis of experimental thrombocytopenic purpura. Arch Pathol. 1970 Sep;90(3):197–205. [PubMed] [Google Scholar]
- JACKSON D. P., SORENSEN D. K., CRONKITE E. P., BOND V. P., FLIEDNER T. M. Effectiveness of transfusions of fresh and lyophilized platelets in controlling bleeding due to thrombocytopenia. J Clin Invest. 1959 Oct;38:1689–1697. doi: 10.1172/JCI103947. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jaffe E. A., Nachman R. L., Becker C. G., Minick C. R. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973 Nov;52(11):2745–2756. doi: 10.1172/JCI107470. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kitchens C. S., Weiss L. Ultrastructural changes of endothelium associated with thrombocytopenia. Blood. 1975 Oct;46(4):567–578. [PubMed] [Google Scholar]
- Saba S. R., Mason R. G. Effects of platelets and certain platelet components on growth of cultured human endothelial cells. Thromb Res. 1975 Nov;7(5):807–812. doi: 10.1016/0049-3848(75)90205-4. [DOI] [PubMed] [Google Scholar]
- Van Horn D. L., Johnson S. A. The mechanism of thrombocytopenic bleeding. Am J Clin Pathol. 1966 Aug;46(2):204–213. doi: 10.1093/ajcp/46.2.204. [DOI] [PubMed] [Google Scholar]
- WOODS M. C., GAMBLE F. N., FURTH J., BIGELOW R. R. Control of the postirradiation hemorrhagic state by platelet transfusions. Blood. 1953 Jun;8(6):545–553. [PubMed] [Google Scholar]