Procoagulant effect of the OKT3 monoclonal antibody: involvement of tumor necrosis factor.
We recently observed that the prophylactic administration of high doses of OKT3 monoclonal antibody (MoAb) in cadaveric renal transplantation favors the development of thromboses of the grafts' main vessels and of thrombotic microangiopathies. These clinical observations led us to perform sequential determinations of plasma levels of prothrombin fragment 1 and 2 (F 1 + 2) and fibrin degradation products (FDP) after the first injection of 5 or 10 mg OKT3 given as prophylaxis in kidney transplant recipients. The values observed have been compared with those of kidney transplant recipients not treated with OKT3. F 1 + 2 levels peaked four hours after the first injection of 5 mg OKT3 (mean +/- SEM: 4.82 +/- 0.73 vs. 1.75 +/- 0.37 nmol/liter in controls, P < 0.01), indicating activation of the common pathway of the coagulation cascade. FDP levels were already above baseline values at four hours and continued to increase until 24 hours (mean +/- SEM at 24 hr, 4729 +/- 879 vs. 1038 +/- 320 ng/ml in controls, P < 0.05), indicating a fibrinolytic process. The magnitude and the time course of the changes in F 1 + 2 and FDP plasma levels were similar whether the patients received 5 or 10 mg dose of OKT3. The levels of von Willebrand factor (VWF) antigen, a molecule released by activated or damaged endothelial cells, were also significantly increased after injection of OKT3 (mean +/- SEM at 24 hr, 3.67 +/- 0.18 vs. 2.17 +/- 0.11 U/ml in controls, P < 0.05). The procoagulant effects of OKT3 were further investigated in vitro on human umbilical vein endothelial cells (HUVEC).(ABSTRACT TRUNCATED AT 250 WORDS)
Pradier
O
O
Department of Immunology, Hematology and Transfusion, Hôpital Erasme, Université Libre de Bruxelles, Belgium.
Marchant
A
A
Abramowicz
D
D
De Pauw
L
L
Vereerstraeten
P
P
Kinnaert
P
P
Vanherweghem
J L
JL
Capel
P
P
Goldman
M
M
D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016030:Kidney Transplantation / Q000009:adverse effects; D007700:Kinetics; D016853:Muromonab-CD3 / Q000008:administration & dosage / Q000009:adverse effects*; D010446:Peptide Fragments / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000209:etiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014841:von Willebrand Factor / Q000378:metabolism
D005338:Fibrin Fibrinogen Degradation Products; D016853:Muromonab-CD3; D010446:Peptide Fragments; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin