High Incidence of Arterial and Venous Thrombosis in Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

OBJECTIVE: To determine the incidence of arterial thrombotic events (ATE) and venous thromboembolism (VTE) in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: This is a retrospective cohort study presenting the incidence of ATE (coronary events or ischemic stroke) and VTE [pulmonary embolism (PE) or deep venous thrombosis (DVT)] in patients diagnosed with AAV between 2005 and 2014. RESULTS: There were 204 patients with AAV who were identified. Median followup for surviving patients was 5.8 (range 1-10) years, accounting for 1088 person-years (PY). The incidence of ATE was 2.67/100 PY (1.56 for coronary events and 1.10 for ischemic stroke) and for VTE was 1.47/100 PY (0.83 for DVT only and 0.64 for PE with/without DVT). On multivariate analysis, prior ischemic heart disease (IHD) and advancing age were the only independent predictors of ATE. Among patients without prior IHD or stroke, the incidence of ATE remained elevated at 2.32/100 PY (1.26 for coronary events and 1.06 for ischemic stroke). ATE, but not VTE, was an independent predictor of all-cause mortality. Event rates for both ATE and VTE were highest in the first year after diagnosis of AAV but remained above the population incidence during the 10-year followup period. In comparison to reported rates for the UK population, the event rates in our AAV patients were 15-times higher for coronary events, 11-times higher for incident stroke, and 20-times higher for VTE. CONCLUSION: Patients with AAV have a high incidence of arterial and venous thrombosis, particularly in the first year after diagnosis.

Bortezomib in ABO-incompatible kidney transplant desensitization: a case report.

Positive B cell crossmatch accompanied by high levels of pre-transplant human leukocyte antigen donor-specific antibodies are associated with adverse graft outcomes in kidney transplant recipients. Targeting plasma cells, the main antibody producing cells, with the proteasome inhibitor bortezomib may be a promising desensitization strategy. We report using a combination of bortezomib and plasmapheresis to desensitize a highly sensitized kidney transplant recipient for an ABO-incompatible living donor kidney transplant. The flow cytometric B cell crossmatch was positive on presentation. After treatment, the anti-A titres fell from 1:64 to 1:4, and a negative B flow cytometric crossmatch was achieved prior to transplantation. The combined approach of bortezomib to abrogate antibody production at the plasma cell level, followed by plasmapheresis and low-dose intravenous immunoglobulin to remove in-circulation alloantibodies, has proven to be effective in our case. Bortezomib may play a role in highly sensitized renal transplants.

Gender discrimination in the influence of hyperglycemia and hyperosmolarity on rat aortic tissue responses to insulin.

Hyperglycaemia initiates endothelial dysfunction causing diabetic macro- and micro-vasculopathy, the main causes of morbidity and mortality in diabetes mellitus. The vasculopathy exhibits gender peculiarities. We therefore explored gender differences in comparing the effects of hyperglycaemia (50 mM) per se with its hyperosmolar (50 mM) effects on vascular tissue responses to insulin. Endothelium-intact or denuded thoracic aortic rings from age-matched male and female Sprague-Dawley rats were incubated for 10 min or 6 h (acute versus chronic exposure) in normal, hyperglycaemic or hyperosmolar Krebs solution. Relaxant responses to insulin (6.9x10(-7)-6.9x10(-5) M) of the phenylephrine-contracted tissues were recorded. Endothelium denudation in both genders inhibited relaxation to insulin in all conditions, more significantly in female than in male tissues, suggesting the female response to insulin is more endothelium-dependent than the male. Acutely and chronically exposed normoglycemic endothelium-intact or -denuded tissues responded similarly to insulin. Chronic hyperglycemic or hyperosmolar exposure did not alter the endothelium-denuded tissue responses to insulin, whereas the responses of the endothelium-intact male and female hyperosmolar, and male hyperglycemic tissues were enhanced. The results show that insulin exerts an endothelium-dependent and independent relaxation with the female tissue responses more endothelium-dependent than the male. The data also suggest that hyperosmolarity per se enhances aortic tissue relaxant responses to insulin whereas hyperglycemia per se inhibits the same and more so in female than male tissues. These effects are endothelium-dependent.