By Todd M. Cooper, DO
2008-12-09
Our improved understanding of the pathophysiology and sequelae of hemoglobinopathies such as sickle cell disease (SCD) has led to improved supportive care and novel therapies. During the oral session on SCD Inflammation and Thrombosis on Sunday, the moderators summarized advances in the areas of inflammation and thrombosis, SCD model systems, and clinical management.
In the session moderated by Drs. Cheryl Hillery and John Strouse, presenters shared their research into SCD-mediated inflammation and thrombosis. Two presentations focused on new experimental models for vaso-occlusive injury. Dr. Lewis L. Hsu observed that hypoxia-reoxygenation in mice leads to oxidative and inflammatory liver injury (abstract #121), while Dr. Jung-Eun Jang shared his mouse model demonstrating that IgG-mediated hemolytic transfusion reaction (HTR) mimics vaso-occlusive crises seen in SCD patients experiencing delayed HTRs (abstract #122). Other abstracts presented in this session revealed novel discoveries in predicting vascular dysfunction in patients with SCD. Elevated triglyceride levels are correlated with intravascular hemolysis and vascular dysfunction. Aldosterone, a hormone regulating renal control of electrolyte distribution, mediates pro-inflammatory effects on vascular endothelium and is a potential target in the management of SCD. The final abstract focused on the hypercoagulable state seen in individuals with SCD. In particular, it described the effects of increased levels of erythrocyte-derived microparticles on Factor XI-dependent thrombin generation in these patients.
The theme of the Monday session titled SCD Model Systems, moderated by Drs. Susan Shurin and Andrew D. Campbell, was the pathophysiology of SCD and HbE disease, emphasizing the use of animal models for preclinical assessment of therapeutics. There was abundant evidence that both inflammation and thrombosis play a prominent role in vaso-occlusive crisis in SCD. Five abstracts used murine models of SCD or HbE. These murine models are used to test new agents that target neutrophil adhesion and stimulate HbF production. Another model examined modulation of nitric oxide metabolism on vascular and erythrocyte biology. One model examined the coagulation pathway in vaso-occlusion to identify potential tissue-protecting properties. The final murine model presented focused on HbE disease and examined changes in structure associated with deoxygenation and association with nitrite. The last abstract of this oral session focused on exciting human stem cell models of erythropoiesis that allow for testing of agents that alter cell developmental biology.
On Monday at 6:00 p.m., Drs. George Atweh and Alexis A. Thompson moderated the Clinical Sickle Cell Disease oral session. These presentations covered important issues in disease prevention and treatment in patients ranging from infants to the elderly. Four of these abstracts shared data on important aspects of neurologic development as well as stroke and silent infarct prevention. Another focused on the elderly, documenting that although there are a significant number of patients that live beyond the average life expectancy for those with SCD, these patients still endure sequelae such as end-organ damage. Finally, Dr. Russell E. Ware shared his data on phenotypic heterogeneity among pediatric patients using hydroxyurea (abstract #709).
These oral sessions provided excellent examples of the exciting progress being made in the SCD management.
Dr. Cooper indicated no relevant conflicts of interest.
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