HYPERFIBRINOLYSIS IN HEPATOSPLENIC SCHISTOSOMIASIS

Aim-To evaluate the nature of accelerated fibrinolysis in hepatospleni c schistosomiasis. Methods-The biological activity of plasminogen (Plg ), plasminogen activators (PA), alpha(2)-antiplasmin (alpha(2)-AP) and plasminogen activator inhibitor-1 (PAI-1) was determined by photometr ic analysis in 15 compensated and 35 decompensated patients with endem ic Egyptian hepatosplenomegaly. Quantitative measurement of plasma con centrations of tissue t-PA, t-PA-PAI-1 complex, alpha(2)-antiplasmin-p lasmin complex (alpha(2)-APP), fibrinogen degradation products (FbDP), D-dimers (D-D), thrombin-antithrombin complex (TAT) and prothrombin f ragment (F 1 + 2) complexes, using double antibody sand,ich enzyme lin ked immunosorbent assays and grading of the degree of hepatic insuffic iency according to the Child-Pugh classification, were also carried ou t. Results-The progressive deterioration of liver function in schistos omal patients, which matched the severity of the disease, led to simul taneous defects in profibrinolytic (decreased Plg and increased PA and t-PA) and antifibrinolytic (decreased alpha(2)-AP and PAI-1) factors- the latter defects being the most prominent-resulting in significant g eneration of plasmin (increased APP complexes) and therefore enhanced fibrinolysis (increased FbDP and D-dimer). The raised concentrations o f FbDP, D-D, TAT and F 1 + 2 established its secondary nature. Conclus ion-These findings suggest that the amount of PAI-1 available to bind and neutralise circulating t-PA may be a critical factor in the progre ss of hyperfibrinolysis observed in hepatosplenic schistosomiasis, and that the pronounced reduction in its plasma concentration may be rega rded as a potential warning indicator of haemostatic imbalance in deco mpensated schistosomal patients at high risk of variceal bleeding.