Acute pancreatitis in Soweto, South Africa: relationship between trypsinogen load, trypsinogen activation, and fibrinolysis.
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.
Segal
Isidor
I
Gastrointestinal Unit, Chris Hani Baragwanath Hospital, Johannesburg, South Africa.
Chaloner
Christopher
C
Douglas
Jessica
J
John
Klaus-Dieter
KD
Zaidi
Amir
A
Cotter
Lawrence
L
Appelros
Stefan
S
Borgström
Anders
A
Braganza
Joan M
JM
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
D011480:Protease Inhibitors; D005337:Fibrin; D014362:Trypsinogen