Antibody-mediated hypercoagulability in the anti-T-cell therapy of transplantation

Research output: Contribution to journalArticle

Abstract

Anti-T-lymphocyte antibodies, used to prevent the acute rejection of renal allografts, include murine OKT3 monoclonal antibody (Mab) and equine ATGAM polyclonal antibody (Pab). The hypercoagulability in 48 renal allograft recipients treated with OKT3 or ATGAM for 10 to 20 d were studied. The clinical transplant protocol involves the two-phase anti-rejection therapy for the patients. During the induction therapy, ATGAM is first administered to the patient for 10-14 d, and from d 3 on cyclosporin A (CyA) is given on a daily basis. The patients are then continually given CyA, but without undergoing the Mab or Pab therapy. If the patient goes into rejection, OKT3 is given along with CyA. On d 3, elevation of fibrin D-dimer to ≤2.1 μg/ml and 1.2 μg/ml was observed, respectively, with the administration of OKT3 and ATGAM (norm ≤80 ng/ml). PAI-1 activity was increased within 24 hr after the infusion of OKT3 or ATGAM. The max concentrations of complement fragment C4d were attained on d 3-5, whereas those of SC5b-9 complex were reached on d 2 and d 6. Bb fragment did not reach its apex until d 6 or 10. Presumably, the alternate pathway was initiated w/o antibody. The pattern of TNF-α release was more complex with considerable variabilities between individuals. In sum, 1) anti-T-cell Mab or Pab therapy leads to a hypercoagulable state, with increases in D-dimer and PAI-1; 2) the classical pathway is activated within 24 hr and is responsible for stimulating monocytes to release cytokines; 3) C5a could stimulate monocytes to yield EL-1 and TNF, which then interact with endothelial cells to release PAI-1 and to upregulate tissue factor expression.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

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Muromonab-CD3
Antilymphocyte Serum
Thrombophilia
T-cells
Cell Transplantation
Cell- and Tissue-Based Therapy
Plasminogen Activator Inhibitor 1
T-Lymphocytes
Antibodies
Cyclosporine
Allografts
Monocytes
Monoclonal Antibodies
Plasminogen Activator Inhibitor 2
Kidney
Transplants
Endothelial cells
Thromboplastin
Clinical Protocols
Immunosuppression

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Antibody-mediated hypercoagulability in the anti-T-cell therapy of transplantation. / Chen, James; Goldman, Mitchell.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

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