A clinical risk score for pulmonary artery thrombosis during acute chest syndrome in adult patients with sickle cell disease

Pulmonary artery thrombosis (PAT) is involved in lung vascular dysfunction during acute chest syndrome (ACS) complicating sickle cell disease (SCD). No clinical score is available to identify patients eligible for multi‐detector computed tomography (MDCT) angiography during ACS. This retrospective study aimed to develop a risk score for PAT during ACS (PAT‐ACS risk score). Patients with SCD were investigated by MDCT during ACS. A logistic regression was performed to determine independent risks factors for PAT and to build the PAT‐ACS risk score. A total of 43 episodes (11·9%) of PAT were diagnosed in 361 episodes of ACS. Multivariate analysis identified four risk factors, which were included in the PAT‐ACS risk score: a baseline haemoglobin >82 g/l, the lack of a triggering factor for ACS, a platelet count >440 × 10⁹/l and a PaCO₂ <38 mmHg at ACS diagnosis. The area under the receiver operating characteristic curve for the PAT‐ACS risk score was 0·74 (95% confidence interval [CI] 0·69–0·79) and differed from that of the revised Geneva score (0·63 (95% CI 0·58–0·69); P = 0·04). The negative predictive value of a PAT‐ACS risk score ≥2 was 94%. In conclusion, we propose a simple clinical risk score to identify SCD patients at high risk of PAT during ACS.     

Secretory phospholipase A2 levels in patients with sickle cell disease and acute chest syndrome

In a multicenter study (eight centers), we determined secretory phospholipase A(2) (sPLA(2)) levels in patients with sickle cell disease and acute chest syndrome (ACS). The diagnosis of ACS was made according to established criteria. The sPLA2 levels were determined in blood samples collected at baseline (time of diagnosis) and serially thereafter up to day 22-35 follow-up visits. Thirty-four of 43 (80%) patients with ACS had enzyme levels > or =1.00 AU at baseline. The enzyme levels decreased significantly on Days 2 through Days 25-35 after baseline. Nine of 43 (20%) patients had baseline sPLA2 values of <1.00 AU with six of them never exceeding 1.00 AU at any point in time during follow-up. The data indicate that the reliability of sPLA(2( for predicting the development of ACS is not perfect (100%) as was previously reported but occurs in about 80% of the patients.     

How I treat acute chest syndrome in children with sickle cell disease

Acute chest syndrome describes new respiratory symptoms and findings, often severe and progressive, in a child with sickle cell disease and a new pulmonary infiltrate. It may be community-acquired or arise in children hospitalized for pain or other complications. Recognized etiologies include infection, most commonly with atypical bacteria, and pulmonary fat embolism (PFE); the cause is often obscure and may be multifactorial. Initiation of therapy should be based on clinical findings. Management includes macrolide antibiotics, supplemental oxygen, modest hydration and often simple transfusion. Partial exchange transfusion should be reserved for children with only mild anemia (Hb > 9 g/dL) but deteriorating respiratory status. Therapy with corticosteroids may be of value; safety, efficacy and optimal dosing strategy need prospective appraisal in a clinical trial. On recovery, treatment with hydroxyurea should be discussed to reduce the likelihood of recurrent episodes.     

Tapered oral dexamethasone for the acute chest syndrome of sickle cell disease

Tapered oral dexamethasone for acute chest syndrome (ACS) in sickle cell anaemia was studied using a novel ACS assessment tool and investigational biomarkers. Twelve participants were randomized (mean age 17·3 years) before early study termination. Dexamethasone decreased duration of hospitalization for ACS by 20·8 h compared to placebo (P = 0·024). Rebound pain occurred in both groups (3 dexamethasone versus 1 placebo). Overall, dexamethasone decreased the leucocyte activation biomarker, sL-selectin; however, participants with rebound pain had higher sL-selectin within 24 h of treatment (dexamethasone or placebo). This ACS assessment tool was feasibly applied, and sL-selectin is a promising biomarker of ACS therapy.     

Lung function and airway hyperresponsiveness in adult patients with sickle cell disease

BACKGROUND: Lung disease is a major cause of morbidity and death in sickle cell disease. Although airway hyperresponsiveness has been noted in children, there are no studies in adult sickle cell patients. The aim of this study was to investigate the prevalence of airway hyperresponsiveness in adult sickle cell patients. METHODS: Twenty-six patients with sickle cell disease (10 HbSC, 9 HbSS, and 7 HbSbeta) were compared with 28 normal control subjects. Pulmonary function tests, including spirometry, measurements of single-breath diffusing capacity and the methacholine challenge test were performed. RESULTS: There were no significant differences in age, gender, or height between groups. Restrictive ventilatory defect was observed in six patients (24%) in the sickle cell disease group. Obstructive ventilatory defect and reduced diffusing lung DLCO capacity was observed in all sickle cell disease subgroups. A positive methacholine challenge test was obtained in eight (31%) sickle cell patients and in two of the 28 controls (7%). CONCLUSION: These features suggest that there is a high prevalence of airway hyperresponsiveness in adult patients with sickle cell disease without a history of reactive airway disease.     

Acute chest syndrome in sickle cell disease

Acute chest syndrome is a common cause of death among patients with sickle cell disease, and an unfamiliar condition to most Australian medical practitioners. We present a case of acute chest syndrome successfully treated with inhaled nitric oxide and exchange transfusion. In the discussion we review current and future management options of acute chest syndrome.     

Pulmonary platelet thrombi and vascular pathology in acute chest syndrome in patients with sickle cell disease

A growing body of evidence suggests a role for platelets in sickle cell disease (SCD). Despite the proinflammatory, occlusive nature of platelets, a role for platelets in acute chest syndrome (ACS), however, remains understudied. To provide evidence and potentially describe contributory factors for a putative link between ACS and platelets, we performed an autopsy study of 20 SCD cases—10 of whom died from ACS and 10 whose deaths were not ACS‐related. Pulmonary histopathology and case history were collected. We discovered that disseminated pulmonary platelet thrombi were present in 3 out of 10 of cases with ACS, but none of the matched cases without ACS. Those cases with detected thrombi were associated with significant deposition of endothelial vWF and detection of large vWF aggregates adhered to endothelium. Potential clinical risk factors were younger age and higher platelet count at presentation. However, we also noted a sharp and significant decline in platelet count prior to death in each case with platelet thrombi in the lungs. In this study, neither hydroxyurea use nor perimortem transfusion was associated with platelet thrombi. Surprisingly, in all cases, there was profound pulmonary artery remodeling with both thrombotic and proliferative pulmonary plexiform lesions. The severity of remodeling was not associated with a severe history of ACS, or hydroxyurea use, but was inversely correlated with age. We thus provide evidence of undocumented presence of platelet thrombi in cases of fatal ACS and describe clinical correlates. We also provide novel correlates of pulmonary remodeling in SCD. Am. J. Hematol. 91:173–178, 2016. © 2015 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.     

Acute chest syndrome: sickle cell disease

Acute chest syndrome (ACS) is a common complication and reason for hospital admission in patients with sickle cell disease (SCD). It is also the most common cause of death in this patient population. Most of the time, the trigger for ACS in an individual patient cannot be identified. However, although infection is the most common identifiable cause for ACS, other important triggers are vaso-occlusive crisis (VOC) and asthma. This comprehensive review will focus on the pathogenesis, clinical characteristics, complications and treatment available to manage ACS. But importantly, this review will highlight new possible etiologies, with the goal of improving oxygenation and, therefore, a reduction in sickling and lung damage in this patient population.     

Acute chest syndrome of adults suffering from sickle cell disease

Sickle cell disease is a common but often poorly understood by chest physicians. The acute chest syndrome represents its main respiratory complication. STATE OF ART: Sickle cell disease is an autosomal recessive disorder inducing, in certain circumstances, sickling of red cells. Natives from western or central Africa and from the Caribbean islands are mainly affected. Acute chest syndrome is defined by the association of chest pain or fever and recent radiographic infiltrates, in patients suffering from sickle cell disease. Determination of etiology, infection, fat embolism or hypoventilation, is difficult, as a self-perpetuating vicious circle is ongoing. Support, largely undervalued, is based on etiological treatment and measures to avoid worsening linked to complications, especially microcirculatory disease. CONCLUSIONS: Acute chest syndrome is a severe respiratory complication of sickle cell disease. Therapeutic measures are simple but undervalued.     

Acute chest syndrome in adults with sickle cell disease

STUDY OBJECTIVES: Acute chest syndrome (ACS) is a frequent and potentially severe pulmonary illness in sickle cell disease (SCD). The aim of the study was to report the clinical features and outcome of consecutive ACS episodes in adult patients in a French SCD center. All patients were treated according to an uniform therapeutic protocol applying transfusion only in the more severe clinical form of ACS. RESULTS: There were 107 consecutive episodes in 77 adult patients (mean age, 29 +/- 7 years; 78% hemoglobin [Hb] SS; 14% Hb SC; and 8% Hb Sbeta + thalassemia) over a 6-year period. Seventy-eight percent of our patients had an associated vaso-occlusive crisis that preceded the chest signs in half of the cases. Comparison between acute and baseline levels showed a statistically significant difference in Hb levels (drop of 1.6 to 2. 25 g/dL depending on Hb genotype), WBC count (increase of 9.2 +/- 8. 3 x 10(9)/L); platelet count (increase of 67 +/- 209 x 10(9)/L); and lactate dehydrogenase values (increase of 358 +/- 775 IU/L) in ACS patients. Hypercapnia was detected in 42% of patients without sign of narcotic abuse. We identified a high percentage of alveolar macrophages containing fat droplets in 31 of 43 (77%) patients who underwent BAL. Bacterial culture findings were almost always negative, but were performed after starting antibiotic therapy that was administered in 96 episodes. Transfusion was required in 50 of 107 ACS events (47%). Five patients died, and all were transfused. CONCLUSIONS: These results confirm that fat embolism is probably a frequent mechanism of ACS in adult patients. However, fat embolism was not associated with a more severe clinical course, suggesting that bronchoscopy and BAL have little impact on the management of these patients. Restricting transfusion to the most severe ACS cases does not seem to increase the mortality rate.     

Temporal relationship of asthma to acute chest syndrome in sickle cell disease

Acute chest syndrome (ACS) is an important cause of mortality and morbidity in children with sickle cell disease (SCD). An association between asthma and ACS has been reported. Our aims were to determine whether asthma was more common in SCD children than controls and the relationship of the timing of the SCD children's first ACS episode to a diagnosis of asthma. One hundred and sixty-five SCD children median age 8.2 (range 0.3-17.3) years and 151 similar ethnic origin and aged controls were prospectively recruited into the study and a detailed history was taken from all of the children to determine if they were taking anti-asthma medication. The medical records of the SCD children were examined to assess whether they had an ACS episode, the age this episode occurred and when any diagnosis of asthma had been made. A similar proportion of the SCD children and controls were taking anti-asthma medication (7% and 9%). Thirty-three SCD children had at least one ACS episode. More of the children who had an ACS compared to those who had not were taking anti-asthma medication (P = 0.02). The ACS children had been diagnosed as asthmatic at a median of 3.5 (range 0.5-7) years prior to their first ACS episode. In conclusion, these results suggest asthma exacerbations may predispose to ACS episodes.     

Phospholipase A2 levels in acute chest syndrome of sickle cell disease

Acute chest syndrome (ACS) is associated with significant morbidity and is the leading cause of death in patients with sickle cell disease (SCD). Recent reports suggest that bone marrow fat embolism can be detected in many cases of severe ACS. Secretory phospholipase A2 (sPLA2) is an important inflammatory mediator and liberates free fatty acids, which are felt to be responsible for the acute lung injury of the fat embolism syndrome. We measured SPLA2 levels in 35 SCD patients during 20 admissions for ACS, 10 admissions for vaso-occlusive crisis, and during 12 clinic visits when patients were at the steady state. Eleven non-SCD patients with pneumonia were also evaluated. To determine if there was a relationship between sPLA2 and the severity of ACS we correlated SPLA2 levels with the clinical course of the patient. In comparison with normal controls (mean = 3.1 +/- 1.1 ng/mL), the non- SCD patients with pneumonia (mean = 68.6 +/- 82.9 ng/mL) and all three SCD patient groups had an elevation of SPLA2 (steady state mean = 10.0 +/- 8.4 ng/mL; vaso-occlusive crisis mean = 23.7 +/- 40.5 ng/mL; ACS mean = 336 +/- 209 ng/mL). In patients with ACS sPLA2 levels were 100- fold greater than normal control values, 35 times greater than values in SCD patients at baseline, and five times greater than non-SCD patients with pneumonia. The degree of SPLA2 elevation in ACS correlated with three different measures of clinical severity and, in patients followed sequentially, the rise in SPLA2 coincided with the onset of ACS. The dramatic elevation of SPLA2 in patients with ACS but not in patients with vaso-occlusive crisis or non-SCD patients with pneumonia and the correlation between levels of SPLA2 and clinical severity suggest a role for SPLA2 in the diagnosis and, perhaps, in the pathophysiology of patients with ACS.     

Acute chest syndrome in adult patients with sickle cell disease: The relationship with the time to onset after hospital admission

Data on acute chest syndrome (ACS) in adult sickle cell disease patients are scarce. In this study, we describe 105 consecutive ACS episodes in 81 adult patients during a 32-month period and compare the characteristics as a function of the time to onset after hospital admission for a vaso-occlusive crisis (VOC), that is early-onset episodes (time to onset ≤24 h, 42%) versus secondary episodes (>24 h, 58%; median [interquartile range] time to onset: 2 [2–3] days). The median age was 27 [22–34] years, 89% of the patients had an S/S or S/β⁰-thalassaemia genotype; 81% of the patients had a history of ACS (median: 3 [2–5] per patient), only 61% were taking a disease-modifying treatment at the time of the ACS. Fever and chest pain were noted in respectively 54% and 73% of the episodes. Crackles (64%) and bronchial breathing (32%) were the main abnormal auscultatory findings. A positive microbiological test was found for 20% of episodes. Fifty percent of the episodes required a blood transfusion; ICU transfer and mortality rates were respectively 29% and 1%. Secondary and early-onset forms of ACS did not differ significantly. Disease-modifying treatments should be revaluated after each ACS episode because the recurrence rate is high.     

Induced sputum versus bronchoalveolar lavage during acute chest syndrome in sickle cell disease

Previous reports have shown that in more than 40% of adults with acute chest syndrome (ACS), fat droplets suggestive of pulmonary fat embolism were present in alveolar macrophages. To determine whether induced sputum (IS) is a reliable test for detecting this embolism, we compared bronchoalveolar lavage and IS results in 20 patients with ACS. We found a correlation between the number of Oil Red O-stained macrophages in sputum and lavage fluid (Spearman's coefficient: rho = 0.657, p < 0.018). Sputum cytology was then studied in another 60 patients who had sickle cell disease with ACS. An elevated percentage of Oil Red O-stained macrophages was found in the sputum of 37/47 patients, but they did not include any of the patients with sickle cell disease but no clinical symptoms. Patients suffering from ACS with Oil Red O-stained macrophages had more extrathoracic concomitant pain than those without (76 vs. 50%, p < 10-8), had more neurologic symptoms (7 vs. 0%, p < 10-8), a lower differential platelet count (-49 +/- 121 vs. +85 +/- 229, p < 0.04), and higher abnormal transaminase values (28 vs. 17%, p < 0.01). We conclude that IS analysis is a safe, noninvasive, and useful test for fat embolism detection in ACS.     

Pulmonary artery pressure and the acute chest syndrome in homozygous sickle cell disease.

OBJECTIVE--To investigate whether attacks of acute chest syndrome affected pulmonary artery pressure in patients homozygous for sickle cell disease. MAIN OUTCOME MEASURES--Pulmonary artery pressure, assessed by non-invasive echocardiographic techniques. PATIENTS--20 patients with homozygous sickle cell disease with a history of at least six episodes of acute chest syndrome and in 20 age, sex, and height matched controls with homozygous sickle cell disease without a history of acute chest syndrome. RESULTS--There was no difference in any of the echocardiographic or Doppler indices between these two groups. CONCLUSIONS--Repeated attacks of acute chest syndrome by the mean age of 12 (range eight to 16) years have not had a discernible effect upon pulmonary artery pressure.