Improved survival in aplastic anemia (AA) has shown a high incidence of late clonal marrow disorders. To investigate whether accelerated senescence of hematopoietic stem cells might underlie the pathophysiology of myelodysplasia (MDS) or paroxysmal nocturnal hemoglobinuria (PNH) occurring as a late complication of AA, we studied mean telomere length (TRF) in peripheral blood leukocytes from 79 patients with AA, Fanconi anemia, or PNH in comparison with normal controls. TRF lengths in the patient group were significantly shorter for age than normals (P < .0001). Telomere shortening was apparent in both granulocyte and mononuclear cell fractions, suggesting loss at the level of the hematopoietic stem cell. In patients with acquired AA with persistent cytopenias (n = 40), there was significant correlation between telomere loss and disease duration (r = −.685; P < .0001), equivalent to progressive telomere erosion at 216 bp/yr, in addition to the normal age-related loss. In patients who had achieved normal full blood counts (n = 20), the rate of telomere loss had apparently stabilised. There was no apparent association between telomere loss and secondary PNH (n = 13). However, of the 5 patients in the study with TRF less than 5.0 kb, 3 had acquired cytogenetic abnormalities, suggesting that telomere erosion may be relevant to the pathogenesis of MDS in aplastic anemia.

Aspirin has an established benefit in reducing the incidence of coronary events and vein graft occlusion. We have now assessed the risk of pre-operative aspirin in a prospective, randomised, double-blind clinical trial in 100 patients scheduled for elective coronary artery surgery. Any prescribed aspirin and non-steroidal anti-inflammatory drugs were discontinued 2 weeks pre-operatively and these were replaced by a randomly assigned tablet of either aspirin 300 mg daily or placebo taken until the day of surgery. Patient compliance was confirmed by serum and urinary salicylate analysis. The two groups were similar in demographic characteristics, bypass time, number of grafts placed and number of internal mammary arteries used. All patients survived to be discharged home (see Table). Aspirin decreases platelet aggregation to arachidonic acid and to collagen both pre- and post-operatively. The benefit of pre-operative aspirin has to be balanced against the risk of increasing post-operative blood loss, re-exploration for excessive bleeding and transfusion requirements.

Objective-To investigate whether monocyte expression of tissue factor is increased in patients with acute coronary syndromes and chronic stable angina.

No abstract