title: Acute pancreatitis in Soweto, South Africa: relationship between trypsinogen load, trypsinogen activation, and fibrinolysis.
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, alpha1 proteinase inhibitor and alpha2 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.
authors: Gastrointestinal Unit, Chris Hani Baragwanath Hospital, Johannesburg, South Africa.
authors: Isidor
authors: I
authors: Segal
authors: Christopher
authors: C
authors: Chaloner
authors: Jessica
authors: J
authors: Douglas
authors: Klaus-Dieter
authors: KD
authors: John
authors: Amir
authors: A
authors: Zaidi
authors: Lawrence
authors: L
authors: Cotter
authors: Stefan
authors: S
authors: Appelros
authors: Anders
authors: A
authors: Borgström
authors: Joan M
authors: JM
authors: Braganza
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005337:Fibrin / Q000032:analysis; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019512:Pancreatitis, Alcoholic / Q000097:blood / Q000378:metabolism* / Q000652:urine; D011480:Protease Inhibitors / Q000097:blood / Q000652:urine; D012720:Severity of Illness Index; D013019:South Africa; D014362:Trypsinogen / Q000097:blood / Q000378:metabolism* / Q000652:urine
chemical_list: D011480:Protease Inhibitors; D005337:Fibrin; D014362:Trypsinogen