Marked elevation of the thrombin generation potential following pulsed steroid therapy in a rabbit experiment

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Heparin is often administered along with pulsed steroid therapy, for preventing thrombosis. However, the effects of steroids on blood coagulability remain to be clarified. To clarify the thrombogenicity of steroids, we measured the thrombogenicity using the thrombin generation test (TGT) before and after administration of pulsed methylprednisolone (m-PSL) injections to rabbits. Among the TGT parameters, the lag time was shortened (0.8±0.11 times) and the ETP (1.39±0.31 times) and peak (1.91±0.69 times) were increased in the pulsed m-PSL group as compared to the control group, indicating a marked increase of the thrombin generation potential (TGP) . Plasma factor VII activity (FVII : C) was increased (1.68±0.47 times) in the pulsed m-PSL group. The increased TGP could be reproduced in vitro by the addition of recombinant activated FVII, but not by that of m-PSL. The increased TGP clearly reflected blood hypercoagulability, caused mainly by the elevated FVII : C induced by the drug. However, neither the soluble fibrin (SF) nor D-dimer levels were increased, indicating the thrombosis was not induced by the steroid therapy alone. Therefore, we propose that heparin use during steroid pulse therapy may be clinically appropriate when thrombotic risk factors are associated with the underlying disease.