Alexis Thompson, MD

2011-01-17

A. Watson and Sarah Armour Endowed Chair for Blood Diseases and Cancer; Head, Hematology Section, Division of Hematology Oncology Transplantation; Director, Comprehensive Thalassemia Program, Children’s Memorial Hospital, Chicago, IL

“This case is reported because of the unusual blood findings, no duplicate of which I have ever seen described. Whether the blood picture represents merely a freakish poikilocytosis or is dependent on some peculiar physical or chemical condition of the blood, or is characteristic of some particular disease, I cannot at present answer. …” – James B. Herrick, MD

The National of Institutes of Health (NIH) marked the 100-year anniversary of the first published case report of sickle cell disease with the James B. Herrick Symposium on November 16 and 17 on the Bethesda campus. The symposium highlighted key milestones in our understanding of sickle cell disease since this initial description (see above), including contributions of sickle cell research toward the advancement of molecular medicine, ongoing challenges in clinical care, and directions of future sickle cell research. National and international experts provided historical and cultural perspectives. The crossroads of race and sickle cell disease were explored by a diverse panel of historians and medical and social scientists. The point of view of the patient was at the forefront of the program, beginning with acknowledgment of Walter Clement Noel, the West Indian dental student who was the subject of Herrick’s paper, and including presentations by adults with sickle cell disease and representatives from sickle cell advocacy groups.

Dr. Francis S. Collins, director of NIH, summarized how programs at NIH represent opportunities to advance the sickle cell research agenda that are likely to facilitate translation of basic science discoveries into new and better therapies. The presentations that followed highlighted current research strategies that have identified potential disease modifiers that may explain phenotypic variations in sickle cell disease and may be targets for new interventions. The XmnI gamma globin gene polymorphism, intergenic HBS1L-MYB sequences, BCL11A, and KLF-1 represent newly discovered fetal globin regulators. Genes that affect pain perception, such as GCH1, may contribute to variances in pain sensitivity among patients with sickle cell.

The global burden of sickle cell disease was underscored: people living in countries with the highest gene frequencies usually do not know that they have sickle cell disease, and, as a consequence, have markedly reduced survival. Many fundamental advances have arisen from research in Africa, including the relative protection of sickle cell trait against malaria and the finding that sickle cell mutations have occurred independently in several populations. Given the high burden of disease in African countries, more collaborative research in Africa was proposed to understand genotype–phenotype relationships, identify additional genetic modifiers, and reduce sickle-cell-related mortality through improvements in detection and care. The international perspective also highlighted sickle cell disease in the African diaspora, including Jamaica and the United Kingdom.

Clinical triumphs and unresolved challenges were summarized: from the adoption of newborn screening across the United States and the success of penicillin prophylaxis in reducing infections, to the capacity of hydroxyurea to alter the course of the disease. While transcranial Doppler ultrasound was cited for markedly reducing strokes in children, much about these early lesions and how they relate to the more daunting brain injuries in overt strokes is still unclear. Clinical and translational research has enhanced our understanding of pulmonary complications of sickle cell including acute chest syndrome, sickle lung disease, and pulmonary hypertension, but more effective therapeutic options are needed.

Attention was focused on sickle cell trait because of its emerging associations with deep-vein thrombosis, chronic renal failure, and adverse pregnancy outcomes, and, even more so, in response to recommendations by the National Collegiate Athletic Association (NCAA) for sickle cell testing of student athletes. The historical context of sickle cell screening was presented as well as the implications of the NCAA ruling for the general population.

Ongoing challenges in the clinical care of adults with sickle cell disease included underutilization of hydroxyurea, barriers to access to care, the lack of comprehensive care programs for adults, and deficiencies in pain management in many care delivery settings. Research that addresses the paucity of new agents for sickle cell, newer strategies for stem cell transplantation, and gene therapy is likely to continue the progress made in the coming years.

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