Hematological and morphological investigation of thrombogenic mechanisms in the lungs of phenylhydrazine-treated rats

• Published in: Experimental and Toxicologic Pathology Vol. 65; no. 4; pp. 457 - 462
• Main Authors: Sato, Hiroko, Sakairi, Tetsuya, Fujimura, Hisako, Sugimoto, Jiro, Kume, Eisuke, Kitamura, Kazuyuki, Takahashi, Kimimasa
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.05.2013; Elsevier BV
• Subjects: Acute toxicity; anemia; Animals; Disease Models, Animal; electron microscopy; erythrocytes; fibrin; fibrinogen; hematology; histopathology; light microscopy; Lung; Lung - drug effects; Lung - pathology; lungs; Male; Microscopy, Electron, Transmission; Oxidants; Oxidants - toxicity; pathogenesis; Phenylhydrazine (PHZ); Phenylhydrazines; Phenylhydrazines - toxicity; prothrombin; Pulmonary Embolism; Pulmonary Embolism - chemically induced; Pulmonary Embolism - pathology; Rat; Rats; Rats, Sprague-Dawley; risk factors; thromboplastin; Thrombosis; Thrombosis - chemically induced; Thrombosis - pathology; Thrombus formation; Thrombus formation; Rat; Lung; Phenylhydrazine (PHZ); Acute toxicity
• ISSN: 0940-2993; 1618-1433; 1618-1433
• DOI: 10.1016/j.etp.2012.01.004

Abnormality in hematological condition including hemolytic disorders has been suggested one of the risk factor of pulmonary thrombosis. We previously reported that phenylhydrazine (PHZ) could induce acute thrombosis in the rat lung. In this study, time-related hematological and histopathological changes were evaluated in PHZ-treated rats to reveal the pathogenesis of pulmonary thrombosis in hemolytic condition. Male Sprague–Dawley rats were administered PHZ at 40mg/kg/day daily for up to 4 days (n=6). At 24h after the last administration (i.e. on days 1, 2, 3, or 4), animals were euthanized and samples were subjected to hematology, light microscopy, and electron microscopy. PHZ-treated rats developed severe anemia on day 1 or later. On day 2 and after, congestion in the alveolar septa corresponding to accumulation of deformed/ghost erythrocytes in the alveolar capillaries was observed, which was the earliest change that preceded thrombus formation. Focal fibrin deposition in the alveolar septa was noted on day 3 and it expanded widely by day 4, while endothelial injury were minimally noted just on day 4. These congestive/thrombotic changes were predominant in the pulmonary capillaries. Changes in hemostatic parameters were noted only on day 4; which were prolonged prothrombin time and activated partial thromboplastin time, greatly increased plasma thrombin–antithrombin complex levels with statistical significance, and slightly decreased fibrinogen levels. In conclusion, the trigger of acute pulmonary thrombosis in PHZ-treated rats was considered to be regional stasis resulting from blockage caused by the deformed erythrocytes, and subsequent systemic hemostatic disruption.