Sickle Cell Disease Acute Chest Research Articles

Enlarged pulmonary artery on computed tomography and respiratory failure in sickle cell disease acute chest syndrome.

Predicting the severity of acute chest syndrome is an important research priority in sickle cell disease. In this retrospective study of patients with acute chest syndrome, an enlarged pulmonary artery on computed tomography was associated with severe respiratory failure defined by the need for either noninvasive or mechanical ventilation.

Hemoglobin Target and Transfusion Modality for Adult Patients With Sickle Cell Disease Acute Chest Syndrome.

Despite the importance of transfusion in treating sickle cell disease acute chest syndrome, the target hemoglobin and optimal modality for transfusion remain unknown. To compare hospital length of stay (LOS) in intensive care unit (ICU) patients with acute chest syndrome transfused to hemoglobin ≥ 8 g/dL versus patients transfused to hemoglobin < 8 g/dL; and to compare hospital LOS in acute chest syndrome patients treated with and without exchange transfusion. We performed a retrospective cohort study of all acute chest syndrome patients treated in the medical ICU at 2 tertiary care hospitals between January 2011 and August 2016 (n = 82). We compared median hospital LOS in patients transfused to hemoglobin ≥ 8 g/dL by the time of ICU transfer to the medical floor versus patients transfused to hemoglobin < 8 g/dL as well as patients who received exchange transfusion versus no exchange transfusion using Wilcoxon rank-sum tests. We modeled the association between hospital LOS and hemoglobin at ICU transfer to the medical floor using multivariable log-linear regression. Median hospital LOS was about half as long for patients transfused to hemoglobin ≥ 8 g/dL versus hemoglobin < 8 g/dL (8.0 versus 16.5 days, P = 0.008). There was no difference in LOS for patients treated with and without exchange transfusion. On average, a 1 g/dL increase in hemoglobin was associated with a 19.5% decrease (95% CI 10.8-28.2%) in LOS, controlling for possible confounding factors. Transfusion to a hemoglobin target ≥ 8 g/dL is associated with decreased hospital LOS in patients with acute chest syndrome. There was no difference in LOS between patients who received exchange transfusion and those who did not.

ENLARGED MAIN PULMONARY ARTERY DIAMETER ON COMPUTED TOMOGRAPHY SCAN ASSOCIATED WITH SEVERE RESPIRATORY FAILURE IN PATIENTS WITH ACUTE CHEST SYNDROME

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Enlarged main pulmonary artery diameter (mPAD) on computed tomography (CT) scan is an underutilized screening test for pulmonary hypertension and is especially useful when echocardiographic estimation of pulmonary arterial (PA) pressure is unavailable. Since estimated PA pressure on transthoracic echocardiogram (TTE) is a known risk factor for mortality in sickle cell disease, we examined the relationship between estimated PA systolic pressure on TTE and mPAD on CT scan in patients with sickle cell disease acute chest syndrome to determine whether enlarged mPAD on CT scan was associated with a high-risk phenotype susceptible to severe respiratory failure. METHODS: We retrospectively reviewed all cases of acute chest syndrome treated in the medical intensive care unit (MICU) at two tertiary care hospitals from January 2011 to August 2016 and included all patients with a CT chest before or during their admission. We calculated the Pearson Correlation Coefficient to determine the correlation between mPAD on CT scan and estimated PA systolic pressure on TTE. We compared demographic characteristics in subjects and then used Fisher’s Exact Test to test whether enlarged mPAD on CT scan, defined as >29 mm in men and >27 mm in women, would be associated with respiratory failure requiring non-invasive or mechanical ventilation in patients with acute chest syndrome. RESULTS: Among 83 MICU admissions for acute chest syndrome, 69 (84%) had a CT chest before or during admission and were included as subjects. The correlation (r) between mPAD on CT scan and estimated PA systolic pressure on TTE was 0.59. 37/69 (54%) subjects had an enlarged mPAD, and were more likely to be older (median age 32 versus 26 years, p<0.01) and female (62.2% versus 37.8%, p=0.02). 14 patients with enlarged mPAD developed respiratory failure requiring noninvasive or mechanical ventilation compared to 3 patients with normal mPAD (p=0.03). 6 patients with enlarged mPAD required mechanical ventilation versus 3 without (p=0.49); and 8 with enlarged mPAD required noninvasive ventilation versus 0 without (p<0.01). CONCLUSIONS: There is a moderate correlation between mPAD on CT scan and estimated PA pressure on TTE in patients with acute chest syndrome. Enlarged mPAD on CT scan in patients with acute chest syndrome is associated with increased risk of respiratory failure requiring non-invasive or mechanical ventilation. CLINICAL IMPLICATIONS: Early identification of pulmonary hypertension can affect clinical management of patients with acute chest syndrome. Main pulmonary artery enlargement on CT scan is a useful screening test for pulmonary hypertension and may allow early identification of patients with acute chest syndrome who are at greater risk of severe respiratory failure requiring noninvasive or mechanical ventilation. DISCLOSURES: No relevant relationships by Dhawani Pandya, source=Web Response No relevant relationships by Joseph Simonson, source=Web Response No relevant relationships by Arunabh Talwar, source=Web Response No relevant relationships by Gulrukh Zaidi, source=Web Response

Role of neutrophils in pulmonary vaso-occlusion during sickle cell disease acute chest syndrome (CAM3P.200)

Abstract Sickle cell disease (SCD) is a hematological disorder that leads to sickling of red blood cells within the microcirculation. The sickle red blood cells (sRBCs) are not only less deformable, but also express α4β1, ICAM-4, Sialyl Lewis X and glycolipids not expressed on non SCD-RBCs. These rigid sRBCs can get sequestered in the microcirculation to cause painful vaso-occlusive crisis (VOC) in SCD patients. In the lung, VOC can contribute to acute chest syndrome, which is a form of acute lung injury. Several factors including the pro-adhesive sRBCs, the large marginated pool of neutrophils, and the hyper-inflammatory state present in SCD can contribute to pulmonary VOC. Although neutrophil-RBC-endothelium interactions are known to play a role in systemic VOC, the cellular mechanism that drives pulmonary VOC remains unknown. Intravital study of the lung microcirculation of live BERK or Townes SCD mice is conducted using two-photon microscopy. Prior to observation, mice are challenged with lipopolysaccharide or PBS to cause lung inflammation and administered (iv) with fluorescent anti-mouse Gr-1 and Ter-119 antibodies to label circulating neutrophils and RBCs, respectively. Vaso-occlusion is defined as cellular aggregation and stasis of blood flow within the lumen of pulmonary capillaries. Preliminary results reveal that circulating macro-aggregates of neutrophils and RBCs may play a role in pulmonary VOC.

Role of neutrophils in pulmonary vaso‐occlusion during sickle cell disease acute chest syndrome (669.6)

Sickle cell disease (SCD) is a hematological disorder that leads to sickling of red blood cells within the microcirculation. The sickle red blood cells (sRBCs) are not only less deformable, but also express α4β1, ICAM‐4, Sialyl Lewis X and glycolipids not expressed on non SCD‐RBCs. These rigid sRBCs can get sequestered in the microcirculation to cause painful vaso‐occlusive crisis (VOC) in SCD patients. In the lung, VOC can contribute to acute chest syndrome, which is a form of acute lung injury. Several factors including the pro‐adhesive sRBCs, the large marginated pool of neutrophils, and the hyper‐inflammatory state present in SCD can contribute to pulmonary VOC. Although neutrophil‐RBC‐endothelium interactions are known to play a role in systemic VOC, the cellular mechanism that drives pulmonary VOC remains unknown. Intravital study of the lung microcirculation of live BERK or Townes SCD mice is conducted using two‐photon microscopy. Prior to observation, mice are challenged with lipopolysaccharide or PBS to cause lung inflammation and administered (iv) with fluorescent anti‐mouse Gr‐1 and Ter‐119 antibodies to label circulating neutrophils and RBCs, respectively. Vaso‐occlusion is defined as cellular aggregation and stasis of blood flow within the lumen of pulmonary capillaries. Preliminary results reveal that circulating macro‐aggregates of neutrophils and RBCs may play a role in pulmonary VOC.Grant Funding Source: Supported by AHA, VMI startup account, and NIH Pulmonary T32 training grant

Comparison of automated red cell exchange transfusion and simple transfusion for the treatment of children with sickle cell disease acute chest syndrome

Both simple transfusion (ST) of packed red blood cells and automated red cell exchange (RCE) are used in the treatment of acute chest syndrome (ACS). We report our experience using each of these modalities for the treatment of ACS. Retrospective chart review of patients with ACS treated with ST only (51 episodes, ST group) or RCE performed either at diagnosis (U-RCE group, 15 episodes) or after ST (ST + RCE group, 15 episodes). The mean clinical respiratory score (CRS) at diagnosis was significantly higher in the U-RCE group than in the ST group, but there were no significant differences among the other groups. The CRS and WBC each decreased significantly after simple transfusion in the ST group and after RCE in the U-RCE group, but both the CRS and WBC increased significantly, and the mean platelet count fell significantly, after simple transfusion in the ST + RCE group. Only patients in the ST + RCE group required mechanical ventilation. There were no significant differences in length of stay (LOS) or total hospital charges among any of the groups, probably due to the small sample size. We conclude that the CRS identifies the patients who are most severely affected with ACS, and that upfront RCE is a safe and effective treatment for these patients. Additional work is needed to develop a method to predict which of the apparently less severely affected patients will fail to improve after simple transfusion and should receive upfront RCE.

Comparison of Erythrocytapheresis and Simple Transfusion for the Treatment of Children with Sickle Cell Disease Acute Chest Syndrome

AbstractAbstract 4765 Introduction:Therapy for acute chest syndrome (ACS) in our hospital includes IV hydration, pain control, antibiotic therapy, incentive spirometry, and an inhaled bronchodilator in patients who are wheezing or who have a history of asthma. Patients also receive red blood cells as either a simple transfusion (ST) or an exchange transfusion using automated erythrocytapheresis (RCE). Here we present clinical and laboratory data from patients with ACS who were treated with RCE and compare these results to a contemporaneous control group of patients with ACS who were treated with ST. Methods:This was a retrospective study of all patients who presented to Arkansas Children’s Hospital from 1996 through 2010 for the treatment of newly diagnosed ACS. Episodes of ACS were separated into a control group who were treated with ST and a RCE group. Patients were referred to the apheresis service by the treating hematologist for RCE when they presented with severe ACS and impending respiratory failure (n=20) or when they failed to improve, or deteriorated, following ST (n=29). Summary statistics were described as mean ± standard deviation for continuous data and frequency and percentage for categorical data. Because there were patients with multiple episodes, repeated measures analyses were performed to evaluate the clinical differences between the RCE and ST episodes. Results:We identified a total of 81 patients who were diagnosed with a total of 119 episodes of ACS. The average age at presentation was 8.5 years (range 5 months to 20 years), 64% were male, and 78% had SS disease. Twelve patients (accounting for 11 episodes each in the RCE and ST groups) had a previous history of asthma and 23 patients had multiple episodes of ACS (median 2, range 2–6). Episodes treated with RCE were significantly more likely to present with tachypnea, retractions, nasal flaring, and decreased air movement but episodes treated with ST were significantly more likely to present with cough and wheezing, even though a previous history of asthma was not more common in the ST group than in the RCE group. The RCE group spent significantly more time on oxygen, eight episodes required BiPAP, and 3 episodes required mechanical ventilation but no ST episodes required either BiPAP or mechanical ventilation. The median WBC at diagnosis was significantly higher in the RCE group but there were no significant differences in hemoglobin level or platelet count between the groups. As expected, blood product utilization was significantly higher in the RCE group. There were no procedural or catheter-related complications in the RCE group. Mean length of stay was not significantly longer in the RCE group but total hospital costs were significantly higher as expected in the RCE group due to the expense of RCE and the need for ICU care, BiPAP, and mechanical ventilation. There were no deaths from ACS during the study period.TableClinical variables in children with ACS treated with RCE or standard transfusion therapyVariableRCE Group (n=49)ST Group (n=70)p-valueRetractions22%9%0.03Nasal flaring14%3%0.049Tachypnea71%46%0.003Decreased air movement20%3%0.005Cough33%53%0.046History of asthma22%16%0.74Wheezing8%21%0.04Initial WBC (K/ml)21.519.90.04Total RBC transfusion volume (ml/kg)53.914.8<0.001Days on oxygen (mean)52.80.001Mean length of stay (days)6.85.40.06Total hospital costs$24,502$14,3090.003Additional variables that were studied but did not differ significantly between the groups included fever, sites of pain, vomiting, grunting, accessory muscle use, crackles, decreased breath sounds, color, oxygen saturation, chest radiograph findings, initial hemoglobin and platelet count, and post-treatment blood counts. Discussion:We found that children treated with RCE were sicker than those treated with ST, as determined by tachypnea, retractions, nasal flaring, decreased air movement, duration of oxygen therapy, need for BiPAP, and need for mechanical ventilation. We also found that children with ACS who present with cough and wheezing are significantly less likely to require RCE. We conclude that RCE is an effective therapy for sicker patients with ACS but that further work is required to develop a predictive scoring system to discriminate prospectively between children with ACS who will benefit from RCE and those who can be treated successfully with ST. Disclosures:No relevant conflicts of interest to declare.