Thrombophilia associated with anti-CD154 monoclonal antibody treatment and its prophylaxis in nonhuman primates1

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Abstract
Background. The authors previously reported thromboembolic complications associated with anti-CD154 monoclonal antibody (mAb) treatment in nonhuman primates. The underlying mechanisms of this complication and its management have not been established. Methods. Eighty cynomolgus monkey renal allograft recipients treated with anti-CD154 mAb were studied for the incidence of thrombosis and its prophylaxis. Results. Without anticoagulation prophylaxis, thromboembolic complications were seen in 5 of 11 recipients. With addition of perioperative heparin, the incidence was decreased to 2 of 10. No further improvement was observed by adding intraoperative prostaglandin (PG) E1. However, addition of ketorolac tromethamine to PGE1 and heparin decreased the incidence of thrombosis (one of eight). Most recently, the authors have found that ketorolac administration alone resulted in no thrombosis in 25 consecutive recipients. Conclusions. Ketorolac is remarkably effective in preventing thromboembolism associated with anti-CD154 mAb treatment, suggesting the mechanism underlying this complication may be related to platelet activation leading to enhanced aggregation.