Table 5.
Immunosuppressants that induced thrombosis after kidney transplantation
| Immunosuppressant | Function | Prothrombotic Effects |
|---|---|---|
| Cyclosporine (calcineurin inhibitors) | Inhibiting Il-2 transcription and T-cell activation | Inducing renal vascular endothelial injury through its nephrotoxicity, which promoted thromboplastin generation, FVIII activation, TXA2 release, platelet activation, and suppressed thrombomodulin activity, hence downregulating the protein C anticoagulant pathway102 Elevating PAI and LDL levels and inducing hypofibrinolysis, which increased thrombogenicity and accelerated atherosclerosis39,103 |
| Tacrolimus (calcineurin inhibitors) | Inhibiting IL-2 release and T-cell activation | Inducing vascular dysfunction by causing increases in vasoconstrictive factors (such as endothelin and thromboxane), activation of the renin-angiotensin system, and decreases in vasodilative factors (such as PGE2, PGI2, and NO)104 |
| High doses of pulsed methylprednisolone (corticosteroid) | Inhibiting the phagocytosis of neutrophils and inducing T-cell apoptosis105 | Inducing overproduction of procoagulant factors106 |
| OKT3 antibody (antithymocyte/antilymphocyte globulin) | Directly targeting the TCR-CD3 complex, which is presently the most potent agent to treat acute renal allograft rejection107 | Inducing TF expression at the surface of both monocytes and endothelial cells, which activated the extrinsic coagulation pathway107 |
| Thymoglobulin (antithymocyte/antilymphocyte globulin) | Inducing lymphocyte depletion in the peripheral blood by activating complement-dependent cell lysis and inducing T-cell apoptosis | Thymoglobulin was not specific for T cells; it contained antibodies directed against platelets, which could activate platelets, inducing thrombosis108 |
| Mycophenolate mofetil (antimetabolite) | Noncompetitive, reversible inhibiting inosine monophosphate dehydrogenase, which is required for purine synthesis during lymphocyte activation109 | Although mycophenolate mofetil did not affect platelet function, it may act as a cofactor in the coagulation cascade, which promoted thrombosis by facilitating the production of Leiden-mutated FV (which cannot be inactivated by protein C)109,110 |
| Azathioprine (antimetabolite) | Azathioprine is converted into six-mercaptopurine which inhibits DNA synthesis, thereby inhibiting lymphocyte proliferation111 | May induce warfarin resistance by enhancing the synthesis of vitamin K–dependent coagulation factors111 |
FVIII, coagulation factor VIII; TXA2, thromboxane A2; PAI, plasminogen activator inhibitor; PGE2, prostaglandin E2; PGI2, prostacyclin; NO, nitric oxide; OKT3, anti-CD3 antibody; TCR, T-cell antigen receptor; FV, coagulation factor V; TF, tissue factor.