HIGH-DOSE GLUCOCORTICOSTEROIDS INCREASE THE PROCOAGULANT EFFECTS OF OKT3

High-dose glucocorticosteroids increase the procoagulant effects of OK T3. The use of OKT3 as prophylaxis in renal transplantation carries an increased risk of intragraft thrombosis, which is related to the syst emic activation of the coagulation system that consistently occurs aft er the first dose of OKT3. As only a few patients develop thrombosis a fter OKT3 therapy, we searched for possible additional risk factor by comparing the demographic and clinical parameters of the 13 patients w ho developed thrombosis in our institution to those of 218 patients wh o did not. Multivariate analysis showed a relationship between the dos e of methylprednisolone (mPDS) given before the first OKT3 injection a nd the risk of thrombosis: 6 out of 42 patients (14%) who received hig h (30 mg/kg) mPDS experienced a thrombotic event, as compared to 7 out of the 189 patients (3.7%) who received less than or equal to 8 mg/kg of mPDS (P < 0.01). This led us to study the effects of mPDS on the p rocoagulant activity induced by OKT3 on peripheral blood mononuclear c ells (PBMC) in vitro. The procoagulant activity of unstimulated PBMC ( mean +/- SEM: 0.6 +/- 0.1 mU/ml) reached 3.0 +/- 0.7 mU/ml after OKT3 stimulation (P = 0.0062) and further increased to 7.4 +/- 2.0 mU/ml wh en PBMC were first preincubated overnight with mPDS before OKT3 stimul ation (P = 0.018 as compared to OKT3 alone). This process involved the tissue factor/ factor VII pathway, as shown by increased membrane exp ression of tissue factor on monocytes as well as by a marked reduction of the induced procoagulant activity when the clotting assay was perf ormed with factor W-deficient plasma. We conclude that high-dose mPDS represents a major risk factor for thrombosis after OKT3 prophylaxis, probably because of the ability of mPDS to potentiate OKT3-induced tis sue factor expression and activity on monocytes.