No abstract

Background In sickle cell disease (SCD), pulmonary hypertension (assessed by tricuspid regurgitant jet [TRJ] velocity ≥ 2.5 m/s) is associated with increased mortality. The relationships between TRJ velocity, left ventricular (LV) and right ventricular (RV) systolic and diastolic function (i.e., relaxation and compliance) have not been well characterized in SCD. Design and Methods Prospective study of 53 ambulatory SCD adults (age, mean: 34 years; range 21-65 years) and 33 African American controls to define the relationship between LV and RV function and TRJ velocity by use of echocardiography. Results SCD subjects had larger left and right atrial volumes and increased LV mass compared to controls. When SCD cases were compared to controls, LV and RV relaxation (i.e., E’) were similar. Among SCD subjects, pulmonary hypertension (TRJ ≥ 2.5 m/s) was present in 40% of cases. Higher TRJ velocity was correlated with larger LA volumes and areas in SCD cases. Additionally, some measures of LV (peak A, lateral and septal annulus E/E’) and RV compliance (TV E/E’) were correlated with TRJ velocity. No other measures of LV/RV systolic function or LV diastolic function (i.e., relaxation and compliance) were associated with TRJ velocity. Conclusions Ambulatory adults with SCD exhibited structural (i.e., LV and RV chamber enlargement) and functional (i.e., higher surrogate measures of LV and RV filling pressure) abnormalities compared to the control group. In SCD subjects, few abnormalities of LV and RV structure/function were associated with TRJ velocity.

Unfortunately, most clinical practice guidelines for the management of acute pain are not based on randomized clinical trials. As a result, our practice of pain management is primarily limited to expert opinion and inferences from observational studies. Additional clinical trials in management of acute pain in children and adults with SCD are critical for the development of evidence-based guidelines.

Sickle cell disease (SCD) is characterized by recurrent episodes of vaso-occlusion, resulting in tissue ischemia and end-organ damage. Inflammation is critical to the pathogenesis of vaso-occlusion and has been associated with SCD-related morbidity and mortality. Despite the impact of inflammation, no directed anti-inflammatory therapies for the treatment or prevention of vaso-occlusive events currently exist. Among individuals with SCD, asthma is a comorbid inflammatory condition that increases the risk of pain episodes, acute chest syndrome and death. Inflammation associated with asthma could augment the proinflammatory state of SCD, increasing episodes of vaso-occlusion. Leukotrienes are inflammatory mediators that play a prominent role in the pathogenesis of asthma and have been associated with SCD-related morbidity. Targeting inflammatory mediators, such as leukotrienes, is a promising approach for the development of novel therapies for the treatment of SCD. This review will examine the relationship between inflammation and vaso-occlusion, with particular focus on the leukotriene pathway.

Baseline level of the cysteinyl leukotriene (CysLT), leukotriene E4 (LTE4), is associated with an increased pain rate in children and adults with sickle cell disease (SCD). To provide additional evidence for a role of CysLTs in the pathogenesis of vaso‐occlusion, we tested the hypothesis that LTE4 levels will increase within an individual during painful episodes compared to baseline. In a cohort of 19 children and adults with SCD, median LTE4 levels increased from 82.36 pg/mg creatinine at baseline to 162.81 pg/mg creatinine during a painful episode (P < 0.001). These data further support a contribution of CysLTs to the process of vaso‐occlusion. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.