Effects Of Immunosuppressants On Coagulation During

An increased risk of thrombosis is associated with some of the immunosuppressant agents. Cyclosporine, for example, has been associated with elevated fibrinogen level, increased platelet aggregation, and von Willebrand factor changes.29 In addition, corticos-teroids have been associated with increased plasminogen activator inhibitor activity.30 Some studies have debated if the use of sirolimus, in combination with cyclosporine or tacrolimus, is associated with an increased risk of hepatic artery thrombosis.4,31--33

Induction therapy with polyclonal anti-thymocyte-globulin (ATG) is widely used in the prophylaxis and treatment of acute allograft rejection. Thrombocytopenia, however, is a major side effect of ATG therapy, and its mechanisms are poorly understood. In Ankersmit's study, the influence of ATG on platelet aggregation was examined aggregometrically.34 Expression of platelet surface activation antigens, CD62P and CD63, was determined by flow cytometry analysis.

Electron microscopy was utilised to determine thrombocyte morphology. Treatment of platelets with ATG markedly induced aggregation, effect that was completely blocked by antibodies against the low-affinity Fc IgG receptor (CD32). Blocking of CD32 abrogates platelet aggregation, therefore, the authors suggest that CD32 plays a crucial role in ATG-induced thrombocytopenia.34

Campath 1H (C1H) is a humanised monoclonal antibody directed against the CD52 antigen that is present on the surface of T cells, B cells, NK cells, and monocytes. It depletes the peripheral blood lymphocytes, preventing an aggressive lymphocytic immune response after transplantation. Adverse events include acute first-dose administration-related reactions (attributed to antibody-induced cytokine release), infectious complications (due to immuno-suppression), and haematological toxicities. Rigor, fever, nausea, vomiting, skin rash, dyspnea, and hypotension are among the most commonly reported infusion-related reactions with alemtuzumab. thrombocytopenia, anaemia, and neutropenia are the most common haematological alterations.35

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