Vascular Lesions in Nine Göttingen Minipigs with Thrombocytopenic Purpura Syndrome

Abstract

Tissues from 9 Göttingen minipigs, aged 7 weeks to 1 year, with clinically diagnosed thrombocytopenic purpura syndrome were examined microscopically. All pigs had a history of spontaneous cutaneous purpura that was generally accompanied by disseminated visceral hemorrhages. Hematologic abnormalities included anemia (8 out of 9 pigs) and thrombocytopenia (7 out of 9 pigs), with platelet counts consistently below 20,000/microl. Microscopically, degenerative vascular lesions with morphologic features of arteriosclerosis were present in all 9 pigs. Vascular lesions affected small- to medium-sized muscular arteries and arterioles in various organs and extraparenchymal tissues; vessels of the renal pelvis and coronary arteries were consistently involved. Microscopic lesions in small- to medium-sized muscular arteries consisted of neointimal proliferation, medial thickening, luminal stenosis, thrombosis, disruption and fragmentation of the internal elastic lamina, necrosis of the tunica media, and medial deposits of myxoid matrix material. Microscopic lesions in arterioles included concentric laminar thickening of vessel walls (onion-skin pattern), endothelial cell hypertrophy, smooth muscle cell vacuolation, necrosis of the tunica media, thrombosis, and partial to complete luminal stenosis. Arteritis and/or periarteritis were also noted in 4 out of 9 pigs. Additional microscopic lesions included membranoproliferative glomerulonephritis (3 out of 9), myocardial microinfarcts (4 out of 7), renal interstitial fibrosis (2 out of 9), extramedullary hematopoiesis (6 out of 9), and intracapillary hyaline thrombi (2 out of 9). Degenerative vascular lesions have not been previously described in Göttingen minipigs with thrombocytopenic purpura syndrome. The etiopathogenesis of both the vascular lesions and thrombocytopenic purpura syndrome is currently unknown.

Swine as Models in Biomedical Research and Toxicology Testing

“…Necrosis of the tunica media and thrombosis occur in some vessels, and lesions have included concentric laminar (onion skin) thickening of vascular walls, with partial to complete luminal stenosis. 23 In severe cases of this syndrome, myocardial infarction with myofiber necrosis and mineralization have been described in the heart as a secondary effect of the vasculitis.…”

“…Mesangioproliferative glomerulopathy, interstitial fibrosis, and tubular atrophy have been described in minipigs with severe thrombocytopenic purpura syndrome. 23 Pigs develop both vesiculoureteral and intrarenal reflux spontaneously and as a surgically produced model. 51 This can limit their utility in some bladder or ureteral surgery applications.…”

Spontaneous Glomerulonephritis in Göttingen Minipigs

“…In this study, the more common renal findings were mononuclear-cell infiltrates; mineralization; tubular basophilia; and presence of eosinophils, casts, and cysts. A recent study, which evaluated 9 cases of vasculopathy in minipigs, described 3 cases of glomerulonephritis (Maratea, Snyder, and Stevenson 2006). Discrimination between normal variation, spontaneous changes, or compound-related changes is fundamental to evaluate the potential toxicity of putative therapeutic agents; the availability of histopathological background data is therefore essential.…”

A Brief Review of Infrequent Spontaneous Findings, Peculiar Anatomical Microscopic Features, and Potential Artifacts in Göttingen Minipigs

“…A generalized condition called spontaneous cutaneous purpura has been reported in GMPs (Maratea, Snyder, and Stevenson 2006;Figure 10), and this forms part of the TP discussed above. Perivascular hemorrhages and small aggregates of macrophages containing hemosiderin are observed in the skin.…”