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Acute pancreatitis in Soweto, South Africa: Relationship between trypsinogen load, trypsinogen activation, and fibrinolysis

Segal, I; Chaloner, C; Douglas, J; John, KD; Zaidi, A; Cotter, L; Appelros, Stefan LU ; Borgström, Anders LU and Braganza, JM (2002) In American Journal of Gastroenterology 97(4). p.883-892
Abstract
Objective: It is not known why acute pancreatitis in Soweto, South Africa, pursues an aggressive course. We sought clues from circulating trypsinogen load at admission as marker of initial acinar injury, trypsinogen activation using the carboxypeptidase B activation peptide as surrogate, proteinase inhibitors, the coagulation-fibrinolysis axis, indicators of inflammation, oxidative stress markers, and antioxidant status. This article reports on the first four aspects. Methods: The study involved 24 consecutive patients with a first attack. All of them were admitted within 24 h, and 22 were alcoholic. Urine was analyzed for anionic trypsinogen and the carboxypeptidase B activation peptide. Serum was tested for anionic and cationic... (More)
Objective: It is not known why acute pancreatitis in Soweto, South Africa, pursues an aggressive course. We sought clues from circulating trypsinogen load at admission as marker of initial acinar injury, trypsinogen activation using the carboxypeptidase B activation peptide as surrogate, proteinase inhibitors, the coagulation-fibrinolysis axis, indicators of inflammation, oxidative stress markers, and antioxidant status. This article reports on the first four aspects. Methods: The study involved 24 consecutive patients with a first attack. All of them were admitted within 24 h, and 22 were alcoholic. Urine was analyzed for anionic trypsinogen and the carboxypeptidase B activation peptide. Serum was tested for anionic and cationic trypsinogen, alpha(1) proteinase inhibitor and alpha(2) macroglobulin. Plasma from a subset was assayed for soluble fibrin, cross-linked fibrin degradation products (surrogates for thrombin and plasmin activity, respectively), and tissue-type plasminogen activator and inhibitor. Results: Soweto controls had higher serum anionic trypsinogen (p=0.004) and plasminogen activator:inhibitor ratio (p=0.047) than U.K. controls. The outcome of acute pancreatitis was mild in 17 but severe in seven with three deaths, two on day 2. In mild pancreatitis, intense plasmin activity (p<0.001) accompanied the surge in trypsinogen, especially anionic (p<0.001), but without increased thrombin activity and in five patients without trypsinogen activation. In severe pancreatitis, further significant increments in plasmin activity and trypsinogens were accompanied by increased thrombin activity (p=0.013) and trypsinogen activation (p=0.046). There was no correlation between surrogates of plasmin and thrombin activity, or between either and the carboxypeptidase B activation peptide. which showed a curvilinear relationship to total serum trypsinogen. Conclusions: The aggressive nature of alcoholic acute pancreatitis in Soweto seems to reflect early profound fibrinolysis, which precedes coagulation and is initially independent of trypsin. Subclinical acinar-cell injury and a profibrinolytic diathesis in outwardly healthy Sowetans may predispose to this problem. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
American Journal of Gastroenterology
volume
97
issue
4
pages
883 - 892
publisher
Wiley-Blackwell
external identifiers
  • wos:000175060000016
  • pmid:12003423
  • scopus:0036117775
ISSN
1572-0241
DOI
10.1016/S0002-9270(02)03960-6
language
English
LU publication?
yes
id
8c22946a-3d94-44bb-ae83-15420917ffd4 (old id 340429)
date added to LUP
2007-11-09 11:09:12
date last changed
2017-01-01 04:45:49
@article{8c22946a-3d94-44bb-ae83-15420917ffd4,
  abstract     = {Objective: It is not known why acute pancreatitis in Soweto, South Africa, pursues an aggressive course. We sought clues from circulating trypsinogen load at admission as marker of initial acinar injury, trypsinogen activation using the carboxypeptidase B activation peptide as surrogate, proteinase inhibitors, the coagulation-fibrinolysis axis, indicators of inflammation, oxidative stress markers, and antioxidant status. This article reports on the first four aspects. Methods: The study involved 24 consecutive patients with a first attack. All of them were admitted within 24 h, and 22 were alcoholic. Urine was analyzed for anionic trypsinogen and the carboxypeptidase B activation peptide. Serum was tested for anionic and cationic trypsinogen, alpha(1) proteinase inhibitor and alpha(2) macroglobulin. Plasma from a subset was assayed for soluble fibrin, cross-linked fibrin degradation products (surrogates for thrombin and plasmin activity, respectively), and tissue-type plasminogen activator and inhibitor. Results: Soweto controls had higher serum anionic trypsinogen (p=0.004) and plasminogen activator:inhibitor ratio (p=0.047) than U.K. controls. The outcome of acute pancreatitis was mild in 17 but severe in seven with three deaths, two on day 2. In mild pancreatitis, intense plasmin activity (p&lt;0.001) accompanied the surge in trypsinogen, especially anionic (p&lt;0.001), but without increased thrombin activity and in five patients without trypsinogen activation. In severe pancreatitis, further significant increments in plasmin activity and trypsinogens were accompanied by increased thrombin activity (p=0.013) and trypsinogen activation (p=0.046). There was no correlation between surrogates of plasmin and thrombin activity, or between either and the carboxypeptidase B activation peptide. which showed a curvilinear relationship to total serum trypsinogen. Conclusions: The aggressive nature of alcoholic acute pancreatitis in Soweto seems to reflect early profound fibrinolysis, which precedes coagulation and is initially independent of trypsin. Subclinical acinar-cell injury and a profibrinolytic diathesis in outwardly healthy Sowetans may predispose to this problem.},
  author       = {Segal, I and Chaloner, C and Douglas, J and John, KD and Zaidi, A and Cotter, L and Appelros, Stefan and Borgström, Anders and Braganza, JM},
  issn         = {1572-0241},
  language     = {eng},
  number       = {4},
  pages        = {883--892},
  publisher    = {Wiley-Blackwell},
  series       = {American Journal of Gastroenterology},
  title        = {Acute pancreatitis in Soweto, South Africa: Relationship between trypsinogen load, trypsinogen activation, and fibrinolysis},
  url          = {http://dx.doi.org/10.1016/S0002-9270(02)03960-6},
  volume       = {97},
  year         = {2002},
}