A 34-year-old African American woman with sickle cell disease and history of relatively severe hemolysis, chronic leg ulcers, and mild pulmonary hypertension presented with a new ischemic stroke. Recent research has suggested a syndrome of hemolysis-associated vasculopathy in patients with sickle cell disease, which features severe hemolytic anemia and leads to scavenging of nitric oxide and its biochemical precursor L-arginine. This diminished bioavailability of nitric oxide promotes a hemolysis-vascular dysfunction syndrome, which includes pulmonary hypertension, cutaneous leg ulceration, priapism, and ischemic stroke. Additional correlates of this vasculopathy include activation of endothelial cell adhesion molecules, platelets, and the vascular protectant hemeoxygenase-1. Some known risk factors for atherosclerosis are also associated with sickle cell vasculopathy, including low levels of apolipoprotein AI and high levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase. Identification of dysregulated vascular biology pathways in sickle vasculopathy has provided a focus for new clinical trials for therapeutic intervention, including inhaled nitric oxide, sodium nitrite, L-arginine, phosphodiesterase-5 inhibitors, niacin, inhaled carbon monoxide, and endothelin receptor antagonists. This article reviews the pathophysiology of sickle vasculopathy and the results of preliminary clinical trials of novel small-molecule therapeutics directed at abnormal vascular biology in patients with sickle cell disease.
Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more
Subscribe for full-text access to content from 1998 forward and a host of useful features
Activate your current subscription (AMA members and current subscribers)
Purchase Online Access to this article for 24 hours
A, The patient had a left medial ankle ulcer of 17 years' duration. B, One day after hospital admission with vaso-occlusive pain crisis, the patient developed a pulmonary infiltrate, encephalopathy, and renal insufficiency. Induced sputum demonstrated lipid-laden macrophages by oil red O stain (magnification × 1000), which is indicative of fat embolus to the lung from infarcted marrow. C, Approximately 2 weeks later, the patient presented with acute dysarthria and right-hand weakness. Diffusion-weighted magnetic resonance imaging (MRI) showed a bright signal in the left hemisphere (left image, arrowhead), indicating acute edema and new stroke. Additional images at the same time using the FLAIR technique (fluid-attenuated inversion recovery) demonstrated right frontal lobe cavitation (right image, left [blue] arrowhead) and chronic watershed zone infarcts (right image, right [yellow] arrowhead) from previously unsuspected ischemic strokes. Magnetic resonance angiography revealed nearly absent flow in the internal carotid arteries (not shown).
apo AI indicates apolipoprotein AI; cGMP, cyclic guanosine monophosphate; CO, carbon monoxide; ET, endothelin; Fe, iron; GTP, guanosine triphosphate; NO, nitric oxide.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 31
Customize your page view by dragging & repositioning the boxes below.
More Listings atJAMACareerCenter.com >
Users' Guides to the Medical Literature
Table 9.2-2 Refuted Evidence From Studies of Physiologic or Surrogate Endpoints
All results at
and access these and other features:
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.