Platelet procoagulant activity induced in vivo by muromonab-CD3 infusion in uremic patients.
BACKGROUND
Muromonab-CD3 is a murine monoclonal antibody (MoAb) that is used in the prophylaxis and treatment of acute graft rejection. Activation of coagulation and fibrinolysis following anti-CD3 administration have been reported in some patients to lead to irreversible intragraft thrombosis.


METHODS
We have studied the effect of muromonab-CD3 infusion on platelets using flow cytometry in six patients who received three daily doses of muromonab-CD3 as prophylaxis of rejection before receiving a living donor renal transplant. Samples were collected before, 15 and 60 min after muromonab-CD3 infusion. Immunolabeling of platelets was performed in whole blood using dual-color analysis. The following conjugated MoAb were used: anti-CD41a, -CD36, -CD42b, -CD62P, -CD63, -factor V/Va and nonspecific Ig. Samples were analyzed with a FACScan flow cytometer (Becton Dickinson, Mountain View, CA, USA).


RESULTS
After muromonab-CD3 infusion, an increase in the binding of MoAb anti-factor V/Va to platelets was seen, which was only statistically significant (2.2% vs. 12.8%, P=.04) after 15 min of the second dose. No significant changes were seen in the other MoAbs studied. No thrombotic complications were observed after transplantation.


CONCLUSIONS
In uremic patients receiving muromonab-CD3 infusion as prophylaxis of graft rejection, an increase in the binding of anti-factor V/Va, denoting an increased exposure of anionic phospholipids in platelets, was seen. This increase in platelet procoagulant activity might contribute to the appearance of thromboses within renal graft seen in some patients who received muromonab-CD3.
Lozano
M
M
Department of Hemotherapy and Hemostasis, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, Villaroel 170, Barcelona 08036, Spain. mlozano@clinic.ub.es
Oppenheimer
F
F
Cofan
F
F
Rosinyol
L
L
Mazzara
R
R
Escolar
G
G
Ordinas
A
A
D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D005165:Factor V / Q000032:analysis / Q000276:immunology; D015943:Factor Va / Q000032:analysis / Q000276:immunology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007263:Infusions, Parenteral; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000008:administration & dosage / Q000494:pharmacology*; D019851:Thrombophilia / Q000139:chemically induced* / Q000209:etiology; D013927:Thrombosis / Q000139:chemically induced / Q000209:etiology; D014511:Uremia / Q000097:blood / Q000188:drug therapy* / Q000628:therapy
D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D015943:Factor Va; D005165:Factor V