Intravascular coagulation in peliosis hepatis in rats
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REDUCED PLATELET AGGREGATION IN CIRRHOSIS: RELATIONSHIP WITH DEFECTIVE PLATELET THROMBOXANE A2 SYNTHESIS. G.La Villa, F.Cominelli, G.Laffi, M.Pinzani, S.Fedi* and P.Gentilini. Clin. Med. IV, *Dipartimento di Fisiopatologia Clinica, University of Florence, ltaly. Patients (pts) with liver cirrhosis often show reduced platelet aggregation. In order to investigate the relationship between platelet aggregation and platelet arachidonic acid (AA) metabolism, we evaluated platelet aggregation in response to ADP, adrenalin, collagen and AA in increasing concentrations (0.75, l.O, 2.0, 2.5, 3.0, 4.0 and 5.0 mM) and measured serum (S-) thromboxane (TX) B2, as an index of platelet TXA2 synthesis during whole blood clotting in 16 pts divided into two groups (group A and B) of 8 pts, according to modified Child's criteria and in 8 controls (group C). Platelet aggregation was determined using an Elvi 840 aggregometer. S-TXB2 was assayed by R.I.A., previous extraction and high pressure liquid chromatographic separation. Statistical analysis was performed using one way analysis of variance. Platelet aggregation in response to AA and collagen was significantly reduced in both patient groups; aggregation in response to ADP and adrenalin was reduced only in group B, but not significantly. S-TXB2 was significantly decreased in the 2 patient groups (group A=I.5+0.3, group B=0.9+0.3, group C=I.85+0.2, ng/l,O00,O00 platelets, mean~SE,pLO.Ol). A significant correlation was also observed between S-TXB2 levels and the extent of platelet aggregation in response to AA (0.75 mM: r=0.47, p/O.05; 2 mM: r=O.51, pLO.Ol; 5mM: r=O.60, p~O.Ol). We conclude that in pts with cirrhosis of the liver: a) platelets have a significantly reduced aggregation in response to AA and collagen; b) platelet TXB2 synthesis is defective and may be related to reduced platelet aggregation. INTRAVASCULAR COAGULATION IN PELIOSIS HEPATIS IN RATS G. L~z&r, E. Husztik ~, E. Szabd~*Institute of Pathophysiology, *Institute of Medical Biology, ~*Department of Dermatology, University Medical School, Szeged, Hungary. The pathogenesis of peliosis hepatis is not clear, although many theories have been sug- gested, e.g.congenital malformation, vascular vericosities, angiitis, focal hepatic necrosis, congestion, or a combination of these causes. The increased risk of peloisis hepatis has been described recently in patients treated with sex steroids, various anabolic steroids and orally administered contraceptives. In the present work the role of the intravaseular coagula- tion was investigated in the pathomechanism of two, experimental forms of peliosis hepatis. Peliosis hepatis was induced in rats with basic polyglutamic acid derivatives or anti-rat glomerular basal membrane rabbit serum in rats presensitized with a rare earth metal complex, neodymium pyrocatechin disulphonate. In both types of peliosis hepatis, severe defibrination with increased level of fibrinogen-fibrin degradation products was detected, and in the cyto- plasm of Kupffer cells and spleen macrophages fibrin--positive materal was immunohistochemical- ly demonstrated. Since macrophages participate in the clearance of the intravascular fibrin aggregates and the rare earth metal compounds, among them the pyrocatechin disulphonate complex of neodymium used in this study, depress the reticulo-endothelial activity, the reti- culoendothelial system may well play a role in the pathogenesis of one of these experimental forms of peliosis hepatis. It is noteworthy that in both experimental forms of peliosis hepatis, as in most human cases, not only the liver but other organs were also involved in the peliotic lesions. $138
Transcript of Intravascular coagulation in peliosis hepatis in rats
REDUCED PLATELET AGGREGATION IN CIRRHOSIS: RELATIONSHIP WITH DEFECTIVE PLATELET THROMBOXANE A2 SYNTHESIS.
G.La Vi l la, F.Cominelli, G.Laffi, M.Pinzani, S.Fedi* and P.Gentilini. Clin. Med. IV, *Dipartimento di Fisiopatologia Clinica, University of Florence, l ta ly.
Patients (pts) with l iver cirrhosis often show reduced platelet aggregation. In order to investigate the relationship between platelet aggregation and platelet arachidonic acid (AA) metabolism, we evaluated platelet aggregation in response to ADP, adrenalin, collagen and AA in increasing concentrations (0.75, l.O, 2.0, 2.5, 3.0, 4.0 and 5.0 mM) and measured serum (S-) thromboxane (TX) B2, as an index of platelet TXA2 synthesis during whole blood clotting in 16 pts divided into two groups (group A and B) of 8 pts, according to modified Child's cr i ter ia and in 8 controls (group C). Platelet aggregation was determined using an Elvi 840 aggregometer. S-TXB2 was assayed by R.I.A., previous extraction and high pressure liquid chromatographic separation. Statistical analysis was performed using one way analysis of variance. Platelet aggregation in response to AA and collagen was significantly reduced in both patient groups; aggregation in response to ADP and adrenalin was reduced only in group B, but not significantly. S-TXB2 was significantly decreased in the 2 patient groups (group A=I.5+0.3, group B=0.9+0.3, group C=I.85+0.2, ng/l,O00,O00 platelets, mean~SE,pLO.Ol). A significant correlation was also observed between S-TXB2 levels and the extent of platelet aggregation in response to AA (0.75 mM: r=0.47, p/O.05; 2 mM: r=O.51, pLO.Ol; 5mM: r=O.60, p~O.Ol). We conclude that in pts with cirrhosis of the l iver: a) platelets have a significantly reduced aggregation in response to AA and collagen; b) platelet TXB2 synthesis is defective and may be related to reduced platelet aggregation.
INTRAVASCULAR COAGULATION IN PELIOSIS HEPATIS IN RATS
G. L~z&r, E. Husztik ~, E. Szabd~*Institute of Pathophysiology, *Institute of Medical Biology, ~*Department of Dermatology, University Medical School, Szeged, Hungary.
The pathogenesis of peliosis hepatis is not clear, although many theories have been sug- gested, e.g.congenital malformation, vascular vericosities, angiitis, focal hepatic necrosis, congestion, or a combination of these causes. The increased risk of peloisis hepatis has been described recently in patients treated with sex steroids, various anabolic steroids and orally administered contraceptives. In the present work the role of the intravaseular coagula- tion was investigated in the pathomechanism of two, experimental forms of peliosis hepatis. Peliosis hepatis was induced in rats with basic polyglutamic acid derivatives or anti-rat glomerular basal membrane rabbit serum in rats presensitized with a rare earth metal complex, neodymium pyrocatechin disulphonate. In both types of peliosis hepatis, severe defibrination with increased level of fibrinogen-fibrin degradation products was detected, and in the cyto- plasm of Kupffer cells and spleen macrophages fibrin--positive materal was immunohistochemical- ly demonstrated. Since macrophages participate in the clearance of the intravascular fibrin aggregates and the rare earth metal compounds, among them the pyrocatechin disulphonate complex of neodymium used in this study, depress the reticulo-endothelial activity, the reti- culoendothelial system may well play a role in the pathogenesis of one of these experimental forms of peliosis hepatis. It is noteworthy that in both experimental forms of peliosis hepatis, as in most human cases, not only the liver but other organs were also involved in the peliotic lesions.
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