The effects of streptokinase in a Chacma baboon (Papio ursinus) model of acquired thrombotic thrombocytopenic purpura

The thrombin generation capability of the Chacma baboon (Papio ursinus): implications for haemostatic disease models

“…The resultant indirect inhibition of fibrin breakdown could not only lessen TTP-associated bleeding in this model but also redirect the actions of plasminogen and tPA away from fibrin clots, allowing more plasminogen and tPA to be available for platelet-VWF binding and degradation than would be expected in humans. This implies that should tPA be considered in a future experiment in this model as was recently suggested 25 , less fibrin binding may occur than would be expected in humans, with the presence of more free tPA for non-fibrin specific effects, such as VWF degradation via plasminogen.…”

“…Although formal TGAs were not performed in any of the preclinical studies conducted in the Chacma baboon model of aTTP 1 , 22 – 25 , nor in any of the recent DIC/sepsis model experiments in this species 2 , 3 , 26 , 27 , it has implications for these models, as well as for the potential investigation of thrombolytic drugs in the aTTP model. Firstly, since thrombin has also been shown to cleave platelet-bound VWF under flow so that excessive and sustained generation of thrombin would restrict the presence of VWF to its release point 28 , a greater overall ETP may explain why (in contrast to clinical experience with TTP in humans) no animal has ever demised or suffered from excessive bleeding, in any of the preclinical studies conducted in this model.…”