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| Year : 1982 | Volume
: 28
| Issue : 4 | Page : 214-7 |
Consumptive coagulopathy and fibrinolysis in experimental acute pancreatitis.
Agarwal MB, Kamdar MS, Bapat RD, Mehta BC, Rao SS, Rao PN
How to cite this article:
Agarwal M B, Kamdar M S, Bapat R D, Mehta B C, Rao S S, Rao P N. Consumptive coagulopathy and fibrinolysis in experimental acute pancreatitis. J Postgrad Med 1982;28:214 |
How to cite this URL:
Agarwal M B, Kamdar M S, Bapat R D, Mehta B C, Rao S S, Rao P N. Consumptive coagulopathy and fibrinolysis in experimental acute pancreatitis. J Postgrad Med [serial online] 1982 [cited 2023 May 28];28:214. Available from: https://www.jpgmonline.com/text.asp?1982/28/4/214/5597 |
The complications of acute pancreatitis include widely disseminated thrombosis in multiple organs of which commonest are the kidneys, lungs, liver and the heart. Pancreas itself undergoes severe necrosis. Although the pathogenesis of pancreatic necrosis is well understood, that of extrapancreatic tissues is obscure. Circulating factors originating from the inflammed pancreas may lead to damage to various organs by variable mechanisms like direct vascular injury, stasis or enhanced intravascular coagulation. The present study was undertaken to evaluate the changes in the coagulation system, fibrinolytic system and alterations in the histopathology of the parenchymatous organs in an experimental model of acute pancreatitis.
The study was carried out on Mongrel dogs under general anaesthesia. The abdomen was opened and the pancreas and duodenum mobilised. A duodenotomy was performed opposite the main pancreatic duct and the duct was cannulated with a venesection cannula. Experimental pancreatitis was induced by injecting a mixture of 1 gramme of trypsin (obtained from beef pancreas and dissolved in 3 ml of water), 5 ml of bile (obtained by puncturing the dog's gall bladder) and 3 ml of blood (obtained from the dog) into the duct and the duodenotomy was closed.[7] Post-operatively, blood samples were collected at every 15 minute intervals for the first one hour and every hourly thereafter for the next 3 hours. A zero hour sample was collected just prior to the injection of trypsin-bile-blood mixture. The occurrence of pancreatitis was confirmed by (a) increasing level of serum amylase and of amylase-creatinine clearance ratio, (b) increased level of amylase in the haemorrhagic ascites that developed, (c) histological study of the pancreas 10 hours after the injection or at death whichever was earlier. Six of the dogs died at the end of 4-10 hours and the remaining were killed after ten hours. Biopsies were taken from the lungs, liver and kidney at the time of autopsy. These organs were studied to see the presence of fibrin thrombi after staining with hematoxylin and eosin and with phosphotungstic acid hematoxylin (PTAH) stains.
The blood samples thus collected were used for haematological and biochemical studies. Complete haemogram, platelet counts, clotting time (C.T.), prothrombin time (P.T.), partial thromboplastin time with Kaolin (PTTK), thrombin time (T.T.), plasma fibrinogen level and euglobulin lysis time (ELT) were studied by the standard techniques on each sample.[1] The control values for various haematological parameters were obtained by sampling normal healthy dogs.
The alterations in the coagulation profile at variable intervals in all the 9 dogs are shown in [Table 1]. Although, there was a marked variation among different dogs, the overall pattern was similar. The changes were indicative of mild consumptive coagulopathy and an effective secondary fibrinolysis.
Disseminated intravascular coagulation (DIC) occurred in all the dogs as evidenced by thrombocytopenia (9 dogs), altered plasma fibrinogen (decrease-6 dogs, increase-2 dogs, initial rise with subsequent fall-1 dog), raised PT (6 dogs), raised PTTK (5 dogs) and raised T.T. (8 dogs). Secondary fibrinolysis as detected by shortened euglobulin lysis time occurred in all.
The pancreatic tissue showed frank changes of acute haemorrhagic pancreatitis in all the nine dogs while the renal, liver and lung tissues showed no evidence of fibrin deposition or vasculitis.
Pancreatic disorders are responsible for significant alterations in the coagulation system. Increased tendency to thrombosis (usually as deep vein thrombosis and occasionally widespread microthrombi) is often recorded in acute pancreatitis and pancreatic carcinoma.[3], [6] However, the clinical studies are often not very rewarding as patients present at variable intervals after the onset of the disease.
Intrapancreatic ductal injection of trypsin-bile-blood mixture is an accepted model for induction of pancreatitis.[7] A similar model was used here. The coagulation studies carried out at regular intervals gave a definite idea about the sequence of events which took place after an insult to the pancreas.
The occurrence of disseminated intravascular coagulation (DIC) was demonstrated in all the dogs as thrombocytopenia together with altered fibrinogen level and a prolonged PT, PTT (K) and/or TT are diagnostic. Thrombocytopenia stood out as an early, severe and one of the most consistent findings. It could be considered as a reliable parameter. The raised fibrinogen in some cases can be explained on the grounds of over-compensated phase of DIC.
It is difficult to explain the exact pathogenesis of DIC in acute pancreatitis. It is believed to be due to the escape of pancreatic enzymes, probably trypsin into the general circulation and the resultant activation of coagulation system.[2], [4] Circulating, heat stable (trypsin like), proteolytic activity is known to increase in pancreatitis[4] and trypsin is known to activate the coagulation cascade.[5] Other pancreatic enzymes i.e. lipase and phospholipase-A have been found to have no significant effect on the coagulation system., Besides trypsin, other proteolytic enzymes, enhanced reticulo-endothelial activity and the extravasation of the plasma coagulant protein due to vasculitis are the other factors which may affect the coagulation systems.[5]
Secondary fibrinolysis is the second important change that takes place in pancreatitis. Markedly shortened euglobulin lysis time and the absence of fibrin-deposition in the microvasculature of the organs favour this process. Besides this, absence of such microthrombi on histology even in the presence of DIC and presence of gross alteration in organ biochemistry favour an extremely effective fibrinolytic system which must have dissolved away all the microthrombi.
It could be thus said that the overall clinical picture of a case of acute pancreatitis depends upon an interplay between the DIC and the fibrinolysis. Cases presenting with thromboembolic episodes may result from a weaker fibrinolytic system.[6] Marked rise in certain coagulation factors (raised fibrinogen, factor V, factor VIII and a shortened P.T.) as found in some clinical studies could mean the same. The correlation of these changes seen in animals with those in human beings remains to be proved.
We are grateful to Dr. C. K. Deshpande, The Dean, Seth G.S. Medical College and K.E.M. Hospital, Bombay for permission to publish this paper. Part of the work was supported by grants from Seth G.S. Medical College and K.E.M. Hospital Research Society.
| 1. | Dace. J. V. and Lewis, S. M.: "Practical Haematology." 5th Edition, The English Language Book Society and Churchill Livingstone, London, 1975, p. 314-420.  |
| 2. | Gabryelewicz, A. and Niewiorowski, S.: Activation of blood clotting and inhibition of fibrinolysis in acute pancreatitis. Thromb. Diath. Haemorrh., 20: 409-414, 1948. |
| 3. | Greipp, P. P., Brown, J. A. and Gralrick, H. R.: Defibrination in acute pancreatitis. Ann. Int. Med., 76: 73-76, 1972. |
| 4. | Kwaan, H. C., Anderson, M. C. and Gramatica, L.: A study of pancreatic enzymes as a factor in the pathogenesis of disseminated intravascular coagulation during acute pancreatitis. Surgery, 69: 663-672, 1971. |
| 5. | Ranson, J. H. C., Lackner, H., Berman, I. R. and Schinella, R.: The relationship of coagulation factors to clinical complications of acute pancreatitis. Surgery, 81: 502-511, 1977. |
| 6. | Shinowara, G. Y., Sbutman, L. J., Welters, M. I., Ruth, M. E. and Walker, E. J.: Hypercoagulability in acute pancreatitis. Amer. J. Surg., 105: 714-719, 1963. |
| 7. | Wright, P. W. and Goodhead, B.: Prevention of haemorrhagic pancreatitis with fibrinolysin or heparin. Arch. Surg., 100: 42-46, 1970. |
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