Hyperfibrinolysis in hepatosplenic schistosomiasis

Abstract

Aim - To evaluate the nature of accelerated fibrinolysis in hepatosplenic schistosomiasis. Methods - The biological activity of plasminogen (Plg), plasminogen activators (PA), α2-antiplasmin (α2-AP) and plasminogen activator inhibitor-1 (PAI-1) was determined by photometric analysis in 15 compensated and 35 decompensated patients with endemic Egyptian hepatosplenomegaly. Quantitative measurement of plasma concentrations of tissue t-PA, t-PA-PAI-1 complex, α2-antiplasmin-plasmin complex (α2-APP), fibrinogen degradation products (FbDP), D-dimers (D-D), thrombin-antithrombin complex (TAT) and prothrombin fragment (F 1+2) complexes, using double antibody sandwich enzyme linked immunosorbent assays and grading of the degree of hepatic insufficiency according to the Child-Pugh classification, were also carried out. Results - The progressive deterioration of liver function in schistosomal patients, which matched the severity of the disease, led to simultaneous defects in profibrinolytic (decreased Plg and increased PA and t-PA) and antifibrinolytic (decreased α2-AP and PAI-1) factors - the latter defects being the most prominent - resulting in significant generation of plasmin (increased APP complexes) and therefore enhanced fibrinolysis (increased FbDP and D-dimer). The raised concentrations of FbDP, D-D, TAT and F 1+2 established its secondary nature. Conclusion - These findings suggest that the amount of PAI-1 available to bind and neutralise circulating t-PA may be a critical factor in the progress of hyperfibrinolysis observed in hepatosplenic schistosomiasis, and that the pronounced reduction in its plasma concentration may be regarded as a potential warning indicator of haemostatic imbalance in decompensated schistosomal patients at high risk of variceal bleeding.