Summary
Human thrombi vary in their susceptibility to lysis and this is clinically important.
Several potential contributory factors were examined in this study by using model
thrombi, created under flow; these provide a robust, reproducible and easily-manipulated
system. Here we identify the plasminogen activators (PA) active in model thrombi of
known age and define the cellular and plasma contribution to activity in different
areas. The cell-rich head of model thrombi had strong thrombin and PA activity, with
coagulant activity also at the tail. Thrombin activity decreased as model thrombi
were aged. PA activity in the thrombus head also decreased on ageing of thrombi but
activity emerged around the thrombi, including the tail. Activity in the head of fresh
model thrombi was primarily due to uPA, with some contribution from tPA. Experiments
with thrombi prepared from platelet-rich plasma and added leucocytes showed that uPA
activity at the head of fresh thrombi was derived from PMN. Older thrombi had tPA
activity around the tail of the thrombus; this activity occurred in the absence of
cells. This study highlights the importance of PMN-derived uPA activity in the lysis
of fresh thrombi, with activity originating in the leucocyte-rich head. It also shows
that thrombi are dynamic structures in which fibrin can be repeatedly laid down and
lysed, observations that are relevant to therapeutic lysis and potential rethrombosis.
Keywords
tPA - uPA - thrombi - fibrinolysis - leucocytes - thrombin
