title: Hypercoagulability in renal transplant recipients. Identifying patients at risk of renal allograft thrombosis and evaluating strategies for prevention.
abstract: Renal transplantation improves survival and quality of life for patients with end-stage renal disease (ESRD). Improvements in immunosuppressive therapy have reduced early allograft loss due to acute rejection to very low levels. Early allograft loss, due to acute thrombotic complications, remains a constant and proportionally increasing complication of renal transplantation. Identifying risk factor(s) for thrombosis amenable to preventive strategies has been elusive. Epidemiological studies have attempted to define risk in terms of modifiable (drugs, dialysis modality, surgical procedure) and non-modifiable (age, diabetes mellitus, vascular anomalies) factors, or identify changes in coagulation or fibrinolysis promoting a more thrombotic state. Most recently the evolution of thrombophilia research has established the potential for inherited hypercoagulability to predispose to acute allograft thrombosis. Inheritance of the factor V Leiden (FVL), prothrombin G20210A mutation, or the presence of antiphospholipid antibodies (APA) may increase the risk of renal allograft thrombosis approximately 3-fold in selected patients. Patients with ESRD due to systemic lupus erythematosus (SLE) appear at particularly high risk of thrombosis, especially if they have either APA or detectable beta(2)-glycoprotein-1. Data for other hypercoagulable states such as hyperhomocystinemia or the C677T polymorphism of the methylenetetrahydrofolate reductase gene are deficient. Patients with APA, FVL, or prothrombin G20210A mutation also appear to have greater graft loss due to vascular rejection, possibly reflecting immunological injury upon the vascular wall exacerbated or induced by the prothrombotic state. While substantial in vitro data suggest cyclosporine is prothrombotic, an independent clinical association with allograft thrombosis is unproven. Interventions to reduce thrombotic risk including heparin, warfarin, and aspirin have been evaluated in both selected high-risk groups (heparin and warfarin) and unselected populations (heparin and aspirin). In unselected patients at low clinical risk, aspirin (75-150 mg/day) with or without a short period of unfractionated heparin (5000U twice a day for 5 days) appears to reduce the risk of renal allograft thrombosis significantly with a low risk of bleeding, especially when compared with low molecular weight heparins which risk accumulation in renal failure. In high-risk groups (identified thrombophilic risk factor, previous thrombosis, or SLE) longer period of heparin, with or without aspirin and maintenance with warfarin, should be considered. Re-transplantation following graft loss due to vascular thrombosis can be undertaken with a low risk of recurrence. Further prospective studies evaluating both putative risk factors and intervention strategies are required to determine whether routine clinical screening for thrombophilic factors is justified.
authors.affiliation: Department of Nephrology, Royal Perth Hospital, Western Australia. ashley.irish@rhealth.wa.gov.au
authors.forename: Ashley
authors.initials: A
authors.lastname: Irish
mesh_terms: D017152:Antibodies, Antiphospholipid / Q000378:metabolism; D001777:Blood Coagulation / Q000502:physiology; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000601:surgery; D016030:Kidney Transplantation; D011183:Postoperative Complications / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control*; D011322:Primary Prevention; D012307:Risk Factors; D019851:Thrombophilia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D013927:Thrombosis / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D014184:Transplantation, Homologous
chemical_list: D017152:Antibodies, Antiphospholipid; D007166:Immunosuppressive Agents