High-dose glucocorticosteroids increase the procoagulant effects of OKT3.
The use of OKT3 as prophylaxis in renal transplantation carries an increased risk of intragraft thrombosis, which is related to the systemic activation of the coagulation system that consistently occurs after the first dose of OKT3. As only a few patients develop thrombosis after OKT3 therapy, we searched for possible additional risk factor by comparing the demographic and clinical parameters of the 13 patients who developed thrombosis in our institution to those of 218 patients who did not. Multivariate analysis showed a relationship between the dose of methylprednisolone (mPDS) given before the first OKT3 injection and the risk of thrombosis: 6 out of 42 patients (14%) who received high (30 mg/kg) mPDS experienced a thrombotic event, as compared to 7 out of the 189 patients (3.7%) who received < or = 8 mg/kg of mPDS (P < 0.01). This led us to study the effects of mPDS on the procoagulant activity induced by OKT3 on peripheral blood mononuclear cells (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 when PBMC were first preincubated overnight with mPDS before OKT3 stimulation (P = 0.018 as compared to OKT3 alone). This process involved the tissue factor/factor VII pathway, as shown by increased membrane expression of tissue factor on monocytes as well as by a marked reduction of the induced procoagulant activity when the clotting assay was performed with factor VII-deficient plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Abramowicz
D
D
Department of Nephrology, Hospital Erasme, Brussels, Belgium.
Pradier
O
O
De Pauw
L
L
Kinnaert
P
P
Mat
O
O
Surquin
M
M
Doutrelepont
J M
JM
Vanherweghem
J L
JL
Capel
P
P
Vereerstraeten
P
P
D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D016030:Kidney Transplantation / Q000009:adverse effects; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000009:adverse effects*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D016853:Muromonab-CD3 / Q000008:administration & dosage / Q000009:adverse effects*; D012307:Risk Factors; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016853:Muromonab-CD3; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin; D008775:Methylprednisolone