Faculty Bibliography

BACKGROUND:The physical properties of a venous thrombus are derived from molecular characteristics, including fibrin polymer diameter, density, branching, and cross-linking. Dense thrombi with thin, highly branched fibrin fibres and small pores in the meshwork have been observed to be more rigid, less permeable, and more resistant to lysis. The three dimensional fibrin meshwork acts as the main structure to entrap and capture erythrocytes, platelets and plasma components. Attached factors become integrated into the developing thrombus, co-localise with fibrin deposition and act in either a pro- or anticoagulant capacity. Similarly, factors including blood flow, osmolarity and pH, oxidative stress, platelet and leukocyte recruitment, and thrombin concentration alter thrombus composition, architecture, and its mechanical properties. CONCLUSIONS:Over time, an increase in thrombus cellular composition and a linear decrease in fibrin content as a function of thrombus age is observed. However, little else is known regarding the evolution of fibrin based clots. The role of fibrin in mediating cellular coordination, thrombus maturation, and changes of the venous wall also requires further research. This review discusses the current impact of fibrin on thrombus remodeling and addresses the limitations of the work done in this area.

BACKGROUND:This is a single institution report of the incidence of combined acute antibody-mediated rejection (ABMR) + acute cellular rejection (ACR) [mixed rejection] in HIV (+) kidney transplant recipients. METHODS:We prospectively enrolled 92 HIV (+) patients who received a kidney transplant between 2001 and 2009. There were three cohorts: no rejection [n=26], ACR [n=53], and mixed rejections (ABMR and ACR) [n=13]. Immunosuppression comprised of basiliximab, cyclosporine, sirolimus, and steroid minimization. Fisher exact tests for categorical variables, t test for continuous variables, and Kaplan-Meier estimates were used to describe events. RESULTS:Mixed rejections were seen in all 13 HIV (+) kidney transplant recipients (14%) with a median time to ABMR of 48 days. Acute cellular rejection occurred in 28% at 1 month and 55% at 12 months. eGFR was lower for recipients who experienced ABMR versus those experiencing ACR and those never experiencing rejection up to 3 years (14 ± 9.4 vs 19 ± 3.3 vs 29 ± 7.3 mL/min, respectively). Kaplan-Meier showed that graft survival up to 9 years was worse in recipients experiencing mixed rejection. Suboptimal donors with terminal creatinine greater than 2.5 mg/dL was associated with increased incidence of mixed rejections versus cellular rejections and no rejection (42% vs 17% vs. 8%, respectively). CONCLUSIONS:Our single center study showed a relatively higher incidence of mixed rejection compared with that reported for non-HIV transplant recipients. A donor terminal serum creatinine greater than 2.5 mg/dL predicted mixed rejection, which was associated with poor outcomes. Donor selection and optimization of immunosuppression may be critical in these patients.