Silent Infarcts, White Matter Integrity, and Oxygen Metabolic Stress in Young Adults With and Without Sickle Cell Trait.

BACKGROUND: Individuals with sickle cell anemia have heightened risk of stroke and cognitive dysfunction. Given its high prevalence globally, whether sickle cell trait (SCT) is a risk factor for neurological injury has been of interest; however, data have been limited. We hypothesized that young, healthy adults with SCT would show normal cerebrovascular structure and hemodynamic function. METHODS: As a case-control study, young adults with (N=25, cases) and without SCT (N=24, controls) underwent brain magnetic resonance imaging to quantify brain volume, microstructural integrity (fractional anisotropy), silent cerebral infarcts (SCI), intracranial stenosis, and aneurysms. Pseudocontinuous arterial spin labeling and asymmetric spin echo sequences measured cerebral blood flow and oxygen extraction fraction, respectively, from which cerebral metabolic oxygen demand was calculated. Imaging metrics were compared between SCT cases and controls. SCI volume was correlated with baseline characteristics. RESULTS: Compared with controls, adults with SCT demonstrated similar normalized brain volumes (SCT 0.80 versus control 0.81, P=0.41), white matter fractional anisotropy (SCT 0.41 versus control 0.43, P=0.37), cerebral blood flow (SCT 62.04 versus control, 61.16 mL/min/100 g, P=0.67), oxygen extraction fraction (SCT 0.27 versus control 0.27, P=0.31), and cerebral metabolic oxygen demand (SCT 2.71 versus control 2.70 mL/min/100 g, P=0.96). One per cohort had an intracranial aneurysm. None had intracranial stenosis. The SCT cases and controls showed similar prevalence and volume of SCIs; however, in the subset of participants with SCIs, the SCT cases had greater SCI volume versus controls (0.29 versus 0.07 mL, P=0.008). Of baseline characteristics, creatinine was mildly elevated in the SCT cohort (0.9 versus 0.8 mg/dL, P=0.053) and correlated with SCI volume (ρ=0.49, P=0.032). In the SCT cohort, SCI distribution was similar to that of young adults with sickle cell anemia. CONCLUSIONS: Adults with SCT showed normal cerebrovascular structure and hemodynamic function. These findings suggest that healthy individuals with SCT are unlikely to be at increased risk for early or accelerated ischemic brain injury.

Quality of life after pharmacomechanical catheter-directed thrombolysis for proximal deep venous thrombosis.

BACKGROUND: After deep venous thrombosis (DVT), many patients have impaired quality of life (QOL). We aimed to assess whether pharmacomechanical catheter-directed thrombolysis (PCDT) improves short-term or long-term QOL in patients with proximal DVT and whether QOL is related to extent of DVT. METHODS: The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial was an assessor-blinded randomized trial that compared PCDT with no PCDT in patients with DVT of the femoral, common femoral, or iliac veins. QOL was assessed at baseline and 1 month, 6 months, 12 months, 18 months, and 24 months using the Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms (VEINES-QOL/Sym) disease-specific QOL measure and the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary general QOL measures. Change in QOL scores from baseline to assessment time were compared in the PCDT and no PCDT treatment groups overall and in the iliofemoral DVT and femoral-popliteal DVT subgroups. RESULTS: Of 692 ATTRACT patients, 691 were analyzed (mean age, 53 years; 62% male; 57% iliofemoral DVT). VEINES-QOL change scores were greater (ie, better) in PCDT vs no PCDT from baseline to 1 month (difference, 5.7; P = .0006) and from baseline to 6 months (5.1; P = .0029) but not for other intervals. SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 2.4; P = .01) but not for other intervals. Among iliofemoral DVT patients, VEINES-QOL change scores from baseline to all assessments were greater in the PCDT vs no PCDT group; this was statistically significant in the intention-to-treat analysis at 1 month (difference, 10.0; P < .0001) and 6 months (8.8; P < .0001) and in the per-protocol analysis at 18 months (difference, 5.8; P = .0086) and 24 months (difference, 6.6; P = .0067). SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 3.2; P = .0010) but not for other intervals. In contrast, in femoral-popliteal DVT patients, change scores from baseline to all assessments were similar in the PCDT and no PCDT groups. CONCLUSIONS: Among patients with proximal DVT, PCDT leads to greater improvement in disease-specific QOL than no PCDT at 1 month and 6 months but not later. In patients with iliofemoral DVT, PCDT led to greater improvement in disease-specific QOL during 24 months.

Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia.

Chronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared with patients not receiving disease-modifying therapy, we prospectively obtained brain magnetic resonance imaging scans with voxel-wise measurements of CBF and OEF in 84 participants with SCA who were grouped by therapy: no disease-modifying therapy, HU, or CTT. There was no difference in whole-brain CBF among the 3 cohorts (P = .148). However, whole-brain OEF was significantly different (P < .001): participants without disease-modifying therapy had the highest OEF (median 42.9% [interquartile range (IQR) 39.1%-49.1%]), followed by HU treatment (median 40.7% [IQR 34.9%-43.6%]), whereas CTT treatment had the lowest values (median 35.3% [IQR 32.2%-38.9%]). Moreover, the percentage of white matter at highest risk for ischemia, defined by OEF greater than 40% and 42.5%, was lower in the HU cohort compared with the untreated cohort (P = .025 and P = .034 respectively), but higher compared with the CTT cohort (P = .018 and P = .029 respectively). We conclude that HU may offer neuroprotection by mitigating cerebral metabolic stress in patients with SCA, but not to the same degree as CTT.

Plasmapheresis for Management of Antiphospholipid Syndrome in the Neurosurgical Patient.

BACKGROUND AND IMPORTANCE: Antiphospholipid syndrome (APS) is an autoimmune disorder associated with a hypercoagulable state and increased risk of intraoperative and postoperative thrombosis. Few neurosurgical studies have examined the management of these patients, though the standard of care in most other disciplines involves the use of anticoagulation therapy. However, this is associated with risks such as hemorrhage, thrombosis due to warfarin withdrawal, and is not compatible with operative intervention. CLINICAL PRESENTATION: We report the cases of 2 antiphospholipid positive patients who were on anticoagulant therapy and underwent surgical bypasses and received perioperative management with plasmapheresis. The first was a 44-yr-old woman who presented with worsening vision, recurring headaches, and a known left internal carotid artery aneurysm that was unsuccessfully treated twice via extracranial to intracranial (ECIC) bypass at another institution. Preoperative tests at our institution revealed elevated beta 2 glycoprotein 1 IgA autoantibodies. The second case was a 24-yr-old woman with previously diagnosed APS, who presented for surgical evaluation of moyamoya disease after sustaining recurrent left hemispheric strokes. Both cases were managed with perioperative plasmapheresis to avoid the need for anticoagulation during the perioperative period, and both underwent successful ECIC bypass procedures without perioperative ischemic or hemorrhagic complications. CONCLUSION: Management of neurosurgical patients with APS can be a precarious proposition. We describe the successful use of plasmapheresis and antiplatelet therapy to better manage patients undergoing neurosurgical procedures, specifically ECIC bypass, and feel this approach can be considered in future cases.

Adherence to iron chelation therapy in patients who switched from deferasirox dispersible tablets to deferasirox film-coated tablets.

OBJECTIVE: To compare real-world adherence to and persistence with deferasirox film-coated tablets (DFX-FCT) and deferasirox dispersible tablets (DFX-DT) among patients who switched from DFX-DT to DFX-FCT, overall and by disease type (sickle cell disease [SCD], thalassemia, and myelodysplastic syndrome [MDS]). METHODS: Patients were ≥2 years old and had ≥2 DFX-FCT claims over the study period and ≥2 DFX-DT claims before the index date (first DFX-FCT claim). The DFX-DT period was defined from the first DFX-DT claim to the index date; the DFX-FCT period was defined from the index date to the end of the study period. Adherence was measured as medication possession ratio (MPR) and proportion of days covered (PDC). Persistence was defined as continuous medication use without a gap ≥30 or 60 days between refills. Comparisons were conducted using paired-sample Wilcoxon sign-rank and McNemar's tests. RESULTS: In total, 606 patients were selected (SCD: 348; thalassemia: 107; MDS: 106; other: 45). Adherence and persistence in the DFX-FCT vs DFX-DT period was significantly higher across all measures: mean MPR was 0.80 vs 0.76 (p < .001); 60.9% vs 54.3% of patients had MPR ≥ 0.8 (p = .009); mean 3-month PDC was 0.83 vs 0.71 (p < .001); 64.2% vs 45.4% of patients had 3-month PDC ≥ 0.8 (p < .001); 87.2% vs 63.4% of patients had 3-month persistence with no gap ≥30 days and 96.1% vs 79.9% with no gap ≥60 days (p < .001). Adherence and persistence improved after switching across all diseases, particularly MDS. CONCLUSIONS: Adherence and persistence improved significantly after switching from DFX-DT to DFX-FCT for all diseases, but especially MDS.

Acute graft-versus-host disease following lung transplantation in a patient with a novel TERT mutation.

Familial pulmonary fibrosis is associated with loss-of-function mutations in telomerase reverse transcriptase (TERT) and short telomeres. Interstitial lung diseases have become the leading indication for lung transplantation in the USA, and recent data indicate that pathogenic mutations in telomerase may cause unfavourable outcomes following lung transplantation. Although a rare occurrence, solid organ transplant recipients who develop acute graft-versus-host disease (GVHD) have very poor survival. This case report describes the detection of a novel mutation in TERT in a patient who had lung transplantation for familial pulmonary fibrosis and died from complications of acute GVHD.

Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis.

BACKGROUND: The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome. METHODS: We randomly assigned 692 patients with acute proximal deep-vein thrombosis to receive either anticoagulation alone (control group) or anticoagulation plus pharmacomechanical thrombolysis (catheter-mediated or device-mediated intrathrombus delivery of recombinant tissue plasminogen activator and thrombus aspiration or maceration, with or without stenting). The primary outcome was development of the post-thrombotic syndrome between 6 and 24 months of follow-up. RESULTS: Between 6 and 24 months, there was no significant between-group difference in the percentage of patients with the post-thrombotic syndrome (47% in the pharmacomechanical-thrombolysis group and 48% in the control group; risk ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.11; P=0.56). Pharmacomechanical thrombolysis led to more major bleeding events within 10 days (1.7% vs. 0.3% of patients, P=0.049), but no significant difference in recurrent venous thromboembolism was seen over the 24-month follow-up period (12% in the pharmacomechanical-thrombolysis group and 8% in the control group, P=0.09). Moderate-to-severe post-thrombotic syndrome occurred in 18% of patients in the pharmacomechanical-thrombolysis group versus 24% of those in the control group (risk ratio, 0.73; 95% CI, 0.54 to 0.98; P=0.04). Severity scores for the post-thrombotic syndrome were lower in the pharmacomechanical-thrombolysis group than in the control group at 6, 12, 18, and 24 months of follow-up (P<0.01 for the comparison of the Villalta scores at each time point), but the improvement in quality of life from baseline to 24 months did not differ significantly between the treatment groups. CONCLUSIONS: Among patients with acute proximal deep-vein thrombosis, the addition of pharmacomechanical catheter-directed thrombolysis to anticoagulation did not result in a lower risk of the post-thrombotic syndrome but did result in a higher risk of major bleeding. (Funded by the National Heart, Lung, and Blood Institute and others; ATTRACT ClinicalTrials.gov number, NCT00790335 .).

Age-Related Emergency Department Reliance in Patients with Sickle Cell Disease.

BACKGROUND: Emergency Department Reliance (EDR: total emergency department [ED] visits/total ambulatory [outpatient + ED] visits) differentiates acute episodic ED users from those who may not have adequate access to outpatient care. OBJECTIVE: This study's aim was to investigate age-related patterns of EDR and associated health-care costs in pediatric patients with sickle cell disease (SCD) and those transitioning from pediatric to adult care. METHODS: State Medicaid data were used for this study. Patients with two or more SCD diagnoses and one or more blood transfusion were included. Quarterly rates of ED visits, EDR, SCD complications associated with ED visits, and ED visits resulting in hospitalization were evaluated. Risk factors associated with high EDR and the association between high EDR and health-care costs were explored through regression analyses. RESULTS: A total of 3208 patients were included. The most common SCD complications associated with ED visits were pain, infection, and pneumonia. Beginning at the age of 15 years, EDR rose from 0.17 to 0.29 visits per quarter at age 22 years, and remained high throughout adulthood. Regression analyses indicated that patients were most likely to have high EDR during the post-transition period and when experiencing an SCD complication. Patients with high EDR incurred statistically significantly higher inpatient and ED costs, resulting in significantly higher total health-care costs. CONCLUSIONS: Compared to children, patients transitioning to adulthood relied more on the ED for their care. In addition, patients with high EDR incurred more days in the hospital and significantly higher health-care costs, highlighting the need to improve transition-related support, including better access to primary care and increased engagement with patients with SCD.

Systemic effects of subcutaneous heparin use in otolaryngology patients.

OBJECTIVES: To describe a population of otolaryngology patients who developed systemic anticoagulation from pharmacologic deep vein thrombosis prophylaxis using subcutaneous low-dose unfractionated heparin and describe associated adverse events and identify risk factors for this occurrence. STUDY DESIGN: Retrospective case series with chart review. SETTING: Single-institution, academic tertiary care center. SUBJECTS AND METHODS: Patients who developed prolonged partial thromboplastin times from routine administration of subcutaneous low-dose unfractionated heparin postoperatively were retrospectively identified during a 16-month period. Data regarding demographics, disease characteristics, laboratory values, associated complications, and risk factors were collected and analyzed. RESULTS: Five patients, all with head and neck cancer, postoperatively developed prolonged partial thromboplastin time levels with prophylactic subcutaneous low-dose unfractionated heparin. All had body mass index ≤ 20 kg/m(2) and received 5000 units of subcutaneous low-dose unfractionated heparin 3 times daily. Four had impaired renal function. Adverse events included 5 postoperative wound hematomas, an emergent reintubation, and a case of persistent mucosal bleeding. These bleeding complications accounted for 25% of all bleeding complications in otolaryngology patients during the same period. CONCLUSION: Unanticipated systemic effects of subcutaneous low-dose unfractionated heparin can cause significant morbidity in surgically treated patients with head and neck cancer. From this case series, risk factors appear to include subcutaneous low-dose unfractionated heparin 3 times daily dose frequency, low body mass index, and renal dysfunction. For this at-risk patient population, a protocol is needed to minimize both deep vein thromboses and complications of prophylactic therapy.

Exertional sickling: questions and controversy.

Sickle cell trait (SCT) occurs in about 8% of African-Americans and is often described to be of little clinical consequence. Over time, a number of risks have emerged, and among these are rare but catastrophic episodes of sudden death in athletes and other individuals associated with physical activities which is often described as exercise collapse associated with sickle trait (ECAST). Despite an epidemiologic link between SCT and sudden death as well as numerous case reports in both medical literature and lay press, no clear understanding of the key pathophysiologic events has been identified. Strategies for identification of individuals at risk and prevention of ECAST have been both elusive and controversial. Stakeholders have advocated for different approaches to this issue particularly with regard to screening for hemoglobin S. Furthermore, the recommendations and guidelines that are in place for the early recognition of ECAST and the prevention and treatment of the illness are not well defined and remain fragmented. Among the cases identified, those in collegiate football players in the United States are often highlighted. This manuscript examines these case studies and the current recommendations to identify areas of consensus and controversy regarding recommendations for prevention, recognition and treatment of ECAST.

Successful orthotopic liver transplantation in an adult patient with sickle cell disease and review of the literature.

Sickle cell disease can lead to hepatic complications ranging from acute hepatic crises to chronic liver disease including intrahepatic cholestasis, and iron overload. Although uncommon, intrahepatic cholestasis may be severe and medical treatment of this complication is often ineffective. We report a case of a 37 year-old male patient with sickle cell anemia, who developed liver failure and underwent successful orthotopic liver transplantation. Both pre and post-operatively, he was maintained on red cell transfusions. He remains stable with improved liver function 42 months post transplant. The role for orthotopic liver transplantation is not well defined in patients with sickle cell disease, and the experience remains limited. Although considerable challenges of post-transplant graft complications remain, orthotopic liver transplantation should be considered as a treatment option for sickle cell disease patients with end-stage liver disease who have progressed despite conventional medical therapy. An extended period of red cell transfusion support may lessen the post-operative complications.

Age-related treatment patterns in sickle cell disease patients and the associated sickle cell complications and healthcare costs.

BACKGROUND: This study explored the blood transfusion patterns, SCD complications, utilization of iron chelation therapies (ICT), healthcare resource use, and costs in pediatric, transitioning (18 years old) and adult patients with SCD. PROCEDURE: Data from Florida (1998-2009), New Jersey (1996-2009), Missouri (1997-2010), Kansas (2001-2009), and Iowa (1998-2010) state Medicaid were used. Patients with ≥2 SCD diagnoses and ≥1 transfusion event were included. Rates of transfusion events, SCD complications, and proportion of eligible patients receiving ICT were calculated. ICT eligibility was defined as receiving ≥10 transfusions over lifetime. SCD complications included pain, pulmonary event, infection event, renal, cardiovascular, stroke, leg ulcers, and avascular necrosis. Regressions were used to assess risk factors for transfusion and identify the main drivers of costs. RESULTS: The sample included 3,208 patients. The transfusion rate increased from 1-year-old to a peak at 16 years old, then dropped until age 26 and remained stable thereafter. In contrast the frequency of diagnoses for SCD complications increased markedly after age 16. Post-transition patients (≥18 years old) were significantly associated with fewer transfusions (odds ratio: 0.80, P = 0.002). Among eligible patients for ICT, there was no statistically significant difference in total cost between the ICT and no ICT groups (adjusted cost difference, $136, P = 0.114). CONCLUSIONS: Patients transitioning to adult care received less transfusions and hydroxyurea, less ICT when eligible for chelation therapy, had higher healthcare costs and suffered from more frequent SCD related complications than pediatric patients. These findings highlight the changes in treatment patterns corresponding to transition to adult care.

Cancer- and chemotherapy-induced anemia.

Anemia is prevalent in 30% to 90% of patients with cancer. Anemia can be corrected through either treating the underlying cause or providing supportive care through transfusion with packed red blood cells or administration of erythropoiesis-stimulating agents (ESAs), with or without iron supplementation. Recent studies showing detrimental health effects of ESAs sparked a series of FDA label revisions and a sea change in the perception of these once commonly used agents. In light of this, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer- and Chemotherapy-Induced Anemia underwent substantial revisions this year. The purpose of these NCCN Guidelines is twofold: 1) to operationalize the evaluation and treatment of anemia in adult cancer patients, with an emphasis on those who are receiving concomitant chemotherapy, and 2) to enable patients and clinicians to individualize anemia treatment options based on patient condition.

Abnormalities in cardiac structure and function in adults with sickle cell disease are not associated with pulmonary hypertension.

BACKGROUND: In sickle cell disease (SCD), pulmonary hypertension (assessed by tricuspid regurgitant jet [TRJ] velocity ≥ 2.5 m/sec) is associated with increased mortality. The relationships among TRJ velocity and left ventricular (LV) and right ventricular (RV) systolic and diastolic function (i.e., relaxation and compliance) have not been well characterized in SCD. METHODS: A prospective study was conducted in 53 ambulatory adults with SCD (mean age, 34 years; range, 21-65 years) and 33 African American controls to define the relationship between LV and RV function and TRJ velocity using echocardiography. RESULTS: Subjects with SCD had larger left and right atrial volumes and increased LV mass compared with controls. When patients with SCD were compared with controls, LV and RV relaxation (i.e., E') were similar. Among subjects with SCD, pulmonary hypertension (TRJ ≥ 2.5 m/sec) was present in 40%. Higher TRJ velocity was correlated with larger left atrial volumes in patients with SCD. Additionally, some measures of LV (peak A, lateral and septal annular E/E' ratio) and RV (tricuspid valve E/E' ratio) compliance were correlated with TRJ velocity. No other measures of LV and 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 with the control group. In subjects with SCD, few abnormalities of LV and RV structure and function were associated with TRJ velocity.

Recurrent, severe wheezing is associated with morbidity and mortality in adults with sickle cell disease.

Prior studies of asthma in children with sickle cell disease (SCD) were based on reports of a doctor-diagnosis of asthma with limited description of asthma features. Doctor-diagnoses of asthma may represent asthma or wheezing unrelated to asthma. Objectives of this study were to determine if asthma characteristics are present in adults with a doctor-diagnosis of asthma and/or wheezing, and to examine the relationship between doctor-diagnosis of asthma, wheezing and SCD morbidity. This was an observational cohort study of 114 adults with SCD who completed respiratory symptom questionnaires and had serum IgE measurements. A subset of 79 participants completed pulmonary function testing. Survival analysis was based on a mean prospective follow-up of 28 months and data were censored at the time of death or loss to follow-up. Adults reporting a doctor-diagnosis of asthma (N = 34) were more likely to have features of asthma including wheeze, eczema, family history of asthma, and an elevated IgE level (all P < 0.05). However, there was no difference in pain or ACS rate, lung function, or risk of death between adults with and without a doctor-diagnosis of asthma. In contrast, adults who reported recurrent, severe episodes of wheezing (N = 34), regardless of asthma, had twice the rates of pain and ACS, decreased lung function and increased risk of death compared with adults without recurrent, severe wheezing. Asthma features were not associated with recurrent, severe wheezing. Our data suggest that wheezing in SCD may occur independently of asthma and is a marker of disease severity.

Sustained response with rituximab in patients with thrombotic thrombocytopenic purpura: a report of 13 cases and review of the literature.

Idiopathic thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease mediated by autoantibodies directed against ADAMTS-13. A number of small series and case reports have shown promising results with rituximab in refractory or relapsed TTP. In this report, we present 13 patients with TTP treated with rituximab. Twelve of the 13 patients (92%) achieved complete response; no subsequent relapses occurred with median follow-up of 24 months (range, 13-84 months). The addition of rituximab to standard therapy appears to be effective in sustaining long-term remission in TTP. However, the optimal dosing and timing of rituximab warrant further investigation. Am. J. Hematol., 2009. (c) 2009 Wiley-Liss, Inc.

Urinary cysteinyl leukotriene E4 significantly increases during pain in children and adults with sickle cell disease.

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.

Urinary cysteinyl leukotriene E(4) is associated with increased risk for pain and acute chest syndrome in adults with sickle cell disease.

Leukotriene E(4) (LTE(4)) levels are associated with rate of pain episodes in children with sickle cell disease (SCD). Because complications of SCD manifest differently in adults than children, we examined a cohort of adults with SCD to determine the relationship between baseline LTE(4) and SCD-related morbidity. Baseline LTE(4) levels were associated with increased rates of pain and acute chest syndrome (ACS) episodes, when those with LTE(4) values in the highest tertile were compared with those in the lowest tertile (pain: risk ratio 7.1, 95% CI 1.8-27.5, P = 0.005; ACS: risk ratio 12.2, 95% CI 2.1-69.8, P = 0.005).