Acute respiratory distress in a patient with sickle-cell anemia]

The acute chest syndrome is a frequent complications of sickle-cell disease characterized by chest pain, fever, and new infiltrate on chest x-ray image. Pathophysiologic factors appear to be multifactorial and better known. We report the case of a 28-year-old woman with homozygous sickle cell anemia who developed acute chest syndrome probably secondary to fat embolism.     

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 of sickle cell disease: new light on an old problem

The pulmonary findings of acute chest syndrome of sickle cell disease have been well characterized in numerous studies. Whereas a third of patients have a documented infection associated with this syndrome, and fat embolism from necrotic marrow is the etiologic factor in another approximately 10%, no cause is discovered in the majority of patients. In most patients, however, the underlying pathophysiology is the presence of a hypoxia-driven, adhesion-related occlusive event in the pulmonary microcirculation. This may be accompanied by a decrease in the levels of normal cytoprotective and anti-adhesive mediators such as nitric oxide. In the patient with sickle cell disease, the lung is also a uniquely vulnerable target organ because its vasculature constricts with hypoxia in contrast to other vascular beds. This review will establish the links between known etiologic agents and the pathophysiology of this syndrome. An additional section of this review will deal with experimental therapies. The use of inhaled nitric oxide will be explored in depth because advances in this area are current and uniquely relevant to acute chest syndrome.     

Perinatal Maternal Mortality in Sickle Cell Anemia: Two Case Reports and Review of the Literature

As outcomes of patients with sickle cell anemia improve and survival into adulthood with good quality of life and expectation of long-term survival becomes more common, challenges have developed, including issues related to reproduction. Pregnancy is frequently complicated in patients with sickle cell anemia with mortality up to 4.0%. Here we report maternal perinatal mortality in two women with sickle cell anemia who died post-partum due to acute chest syndrome (ACS), caused by bone marrow fat embolism and review the literature pertinent to this subject. Patient A was a 28-year-old woman with sickle cell anemia with multiple complications. At 30 weeks’ gestation she developed hemolysis associated with poor placental function necessitating delivery by C-section. The fetus was delivered successfully but she died due to multi organ failure after delivery. Autopsy showed pulmonary and amniotic fluid embolization. Patient B was a 37-year-old woman with uncomplicated sickle cell anemia who presented with pre term labor and crisis, then ACS and fetal distress. The infant was delivered successfully but the patient died after cardiovascular collapse. Autopsy results showed fat and bone marrow embolization as the cause of death. Pregnancy continues to be high risk for patients with sickle cell anemia including those with mild disease. Maternal perinatal mortality could be unpredictable due to serious complications of sickle cell disease. More studies to assess maternal perinatal mortality are needed.     

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.     

Increased F2 isoprostanes in the acute chest syndrome of sickle cell disease as a marker of oxidative stress.

Nitric oxide metabolism is altered during the acute chest syndrome of sickle cell disease. In the presence of oxygen and oxygen-related molecules, nitric oxide can preferentially form the powerful oxidants nitrite, nitrate, and peroxynitrite. We hypothesized that increased oxidative stress may contribute to the pathogenesis of acute chest syndrome and measured F2 isoprostanes, a nonenzymatically generated molecule resulting from free radical catalyzed lipid peroxidation in patients with sickle cell disease in various stages of disease. Plasma samples were obtained from nineteen patients with sickle cell disease during acute chest syndrome (pre- and postexchange transfusion), vasoocclusive crisis, and/or at baseline; 12 normal volunteers served as controls. F2 isoprostanes were measured by gas chromatography/mass spectrophotometry. There was a 9-fold increase in F2 isoprostanes in patients with acute chest syndrome as compared with normal volunteers. There was approximately a 50-60% decline in isoprostanes postexchange transfusion to a level similar to that of patients with sickle cell disease at baseline. There was no difference in isoprostanes between vasoocclusive crisis and patients with sickle cell disease at baseline. Increased oxidative stress, measured by generation of F2 isoprostanes, occurs during acute chest syndrome and may have an important role in the pathogenesis of this disease process.     

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.     

Dural venous sinus thrombosis in a patient with sickle cell disease: case report and literature review

We report a case of dural venous sinus thrombosis (DVST) in a patient who developed seizures following exchange transfusion for treatment of acute chest syndrome associated with sickle cell disease. Evaluation with magnetic resonance imaging and magnetic resonance venography of the brain indicated left sigmoid sinus thrombosis. The history and laboratory evaluation did not reveal any other inherited or acquired hypercoagulable states. This is the fourth case of dural venous sinus thrombosis associated with sickle cell disease reported in literature. The patient had a favorable outcome with early treatment of unfractionated heparin.     

Sickle cell patient with an acute chest syndrome and a negative chest X-ray: potential role of the ventilation and perfusion (V/Q) lung scan

Acute chest syndrome (ACS) in sickle cell disease is caused by thromboemboli in the pulmonary vasculature. The diagnostic criteria include the presence of pulmonary infiltrate(s) on chest x-ray. This case report suggests that a V/Q scan may play a diagnostic role in sickle cell patients with symptoms of ACS and a negative chest x-ray.     

Coexistence of sickle cell disease and severe congenital neutropenia: first impressions can be deceiving

We report an Omani family in whom the propositus had a rare coexistence of sickle cell disease and severe congenital neutropenia associated with a mutation in ELANE. In contrast to his siblings with sickle cell disease, the severity of HbSS-associated complications such as painful crises and acute chest syndrome was significantly reduced. His course of the disease had markedly worsened after initiating G-CSF therapy. These clinical observations suggest that neutropenia may ameliorate inflammatory responses and thus display a modulating factor with respect to the clinical course of sickle cell disease.     

Hemorheological risk factors of acute chest syndrome and painful vaso-occlusive crisis in children with sickle cell disease

Background

Little is known about the effects of blood rheology on the occurrence of acute chest syndrome and painful vaso-occlusive crises in children with sickle cell anemia and hemoglobin SC disease.

Design and Methods

To address this issue, steady-state hemorheological profiles (blood viscosity, red blood cell deformability, aggregation properties) and hematologic parameters were assessed in 44 children with sickle cell anemia and 49 children with hemoglobin SC disease (8-16 years old) followed since birth. Clinical charts were retrospectively reviewed to determine prior acute chest syndrome or vaso-occlusive episodes, and rates of these complications were calculated.

Results

Multivariate analysis revealed that: 1) a higher steady-state blood viscosity was associated with a higher rate of vaso-occlusive crises in children with sickle cell anemia, but not in children with hemoglobin SC disease; 2) a higher steady-state red blood cell disaggregation threshold was associated with previous history of acute chest syndrome in children with hemoglobin SC disease and boys with sickle cell anemia.

Conclusions

Our results indicate for the first time that the red blood cell aggregation properties may play a role in the pathophysiology of acute chest syndrome in children with hemoglobin SC disease and boys with sickle cell anemia. In addition, whereas greater blood viscosity is associated with a higher rate of vaso-occlusive crises in children with sickle cell anemia, no association was found in children with hemoglobin SC disease, underscoring differences in the etiology of vaso-occlusive crises between sickle cell anemia and hemoglobin SC disease.Key words: sickle cell anemia, hemoglobin SC disease, red blood aggregation, blood viscosity, red blood cell deformability     

Sickle acute lung injury: role of prevention and early aggressive intervention strategies on outcome

Acute chest syndrome in sickle cell disease is a form of acute lung injury that may progress to acute respiratory distress syndrome and death. Despite recent advances in diagnosis and treatment that have resulted in improved survival in sickle cell disease, acute chest syndrome remains the most common cause of death in this population. The current standards of treatment for acute chest syndrome have been reviewed. Biomedical re-search forms the basis for sound clinical decision making and implementation of interventions that target prevention, diagnosis, and effective treatment options. Although current clinical trials are ongoing to address several new potential therapeutic options,more research using preventative and interventional strategies in sickle acute lung injury is warranted.     

Results of bronchoscopically obtained lower airway cultures from adult sickle cell disease patients with the acute chest syndrome

PURPOSE: The purpose of this study was to determine the frequency of bacterial pneumonia as a cause of the acute chest syndrome in adult patients with sickle cell disease based on bronchoscopically obtained lower airway cultures and to describe the clinical, laboratory, and roentgenographic features of the acute chest syndrome in a series composed entirely of adult patients with sickle cell disease. PATIENTS AND METHODS: We reviewed the hospital records from 19 episodes (18 patients) of acute chest syndrome in adult patients with sickle cell disease (greater than or equal to 19 years of age) who had undergone flexible bronchoscopy to obtain lower airway cultures between January 1979 and July 1987. We also recorded patients' clinical, laboratory, and roentgenographic characteristics. RESULTS: Pneumonia was diagnosed in four of 19 episodes (21%) of acute chest syndrome based on quantitative cultures obtained at bronchoscopy. The pneumonia was caused by Streptococcus pneumoniae in two patients and mixed aerobic and anaerobic organisms in the other two patients. Forty-four of 45 blood cultures were negative, and one grew Staphylococcus epidermidis, which was considered a contaminant. Chest roentgenograms revealed lower lobe involvement in 17 episodes (90%) and bilateral infiltrates in six (32%). Pleural effusions occurred in seven episodes (37%), and pleural fluid samples obtained from five of these revealed sterile exudates. CONCLUSION: The results of this retrospective study suggest that bacterial pneumonia is an uncommon cause of acute chest syndrome in adult patients with sickle cell disease. These results are consistent with previous retrospective studies using noninvasive techniques to diagnose pneumonia. Nevertheless, there appeared to be no reliable noninvasive variables that could accurately differentiate between patients with and without pneumonia and, consequently, we recommend empiric antibiotic therapy in addition to usual supportive care of these patients.     

Fat embolism syndrome associated with asthma and sickle cell-β+-thalassemia

A 25-year-old African-American man with sickle cell-β⁺-thalassemia presented with acute asthma of 2 days' duration. The asthma was well controlled by 48 hr, and parenteral medications were changed to oral bronchodilators and steroids. Sixty hours after presentation, he developed pain similar to that of sickle cell vasooclusion, for which he received small amounts of analgesics. He died approximately 84 hours after presentation. Autopsy showed extensive marrow necrosis and massive fat embolism. This is the first reported case of fat embolism syndrome associated with this genotype, the mildest of the clinically significant sickle cell hemoglobinopathies. The relationship between these etiologic factors and indications for transfusions are discussed. © 1994 Wiley-Liss, Inc.     

The Role of Inflammation and Leukocytes in the Pathogenesis of Sickle Cell Disease

Acute and chronic vascular occlusion underlies much of the morbidity and mortality in sickle disease. Abnormal polymerization of deoxygenated hemoglobin S (HbS) resulting in stiff, non-deformable erythrocytes is central to sickle cell pathogenesis. However, a complex interplay of many factors determines the balance between adequate blood flow and vessel obstruction. Serum markers of inflammation have provided evidence for a state of chronic inflammation in sickle cell disease (SCD). Inflammation promotes endothelial adherence to sickle erythrocytes. Studies demonstrating a beneficial effect of steroid therapy for painful episodes and acute chest syndrome provide indirect evidence for the role of inflammation in this disease. Leukocytosis, in the absence of infection, is common in SCD patients and predicts for stroke, acute chest syndrome, and overall mortality. Neutrophils and monocytes have been shown to be activated in these patients. Activated leukocytes further promote vascular inflammation and vessel damage. A reduction in leukocytes, and thus inflammation, may partially explain the beneficial effects of hydroxyurea in this disease. These data provide a strong rationale for clinical studies of therapy directed at inflammation and/or leukocytes in sickle cell disease.     

The Role of Inflammation and Leukocytes in the Pathogenesis of Sickle Cell Disease; Haemoglobinopathy

Acute and chronic vascular occlusion underlies much of the morbidity and mortality in sickle disease. Abnormal polymerization of deoxygenated hemoglobin S (HbS) resulting in stiff, non-deformable erythrocytes is central to sickle cell pathogenesis. However, a complex interplay of many factors determines the balance between adequate blood flow and vessel obstruction. Serum markers of inflammation have provided evidence for a state of chronic inflammation in sickle cell disease (SCD). Inflammation promotes endothelial adherence to sickle erythrocytes. Studies demonstrating a beneficial effect of steroid therapy for painful episodes and acute chest syndrome provide indirect evidence for the role of inflammation in this disease. Leukocytosis, in the absence of infection, is common in SCD patients and predicts for stroke, acute chest syndrome, and overall mortality. Neutrophils and monocytes have been shown to be activated in these patients. Activated leukocytes further promote vascular inflammation and vessel damage. A reduction in leukocytes, and thus inflammation, may partially explain the beneficial effects of hydroxyurea in this disease. These data provide a strong rationale for clinical studies of therapy directed at inflammation and/or leukocytes in sickle cell disease.     

Myocardial injury or infarction associated with fat embolism in sickle cell disease: a report of three cases with survival

Fat embolism represents a dread complication of sickle cell hemoglobinopathies. We present the details of three cases that, in addition to an acute chest syndrome, had serological and clinical parameters consistent with myocardial damage. A favorable outcome was obtained with judicious use of blood transfusion.     

Sickle cell chronic lung disease: prior morbidity and the risk of pulmonary failure

Sickle cell chronic lung disease (SCLD) is a prime contributor to mortality in young adult patients with sickle cell disease, especially those with sickle cell anemia (SS). Both perfusion and diffusion defects have been demonstrated, with generalized pulmonary fibrosis and disabling restrictive lung failure. We report 28 cases (25 SS, 1 S beta(0) thalassemia, 1 S beta(+) thalassemia and 1 SO-Arab) which began during the second decade of life and which ended in death by the fourth decade, after an ordered progression to pulmonary failure and cor pulmonale. Myocardial hypoxia with multifocal fibrosis and segmental infarction occurred in more than one-third of the cases and sudden death was a frequent final event. We define 4 stages of SCLD, based on pulmonary function tests, chest roentgenograms, blood gases, and noninvasive cardiac studies; each stage is 2 or 3 years in length, until death ensues in Stage 4. Case-control analysis showed that the significant risk factors associated with SCLD are 1) the total number of acute chest syndrome events in an individual before the onset of SCLD, (p = 0.0001), 2) sickle cell crisis marked by chest pain (p = 0.03) and 3) aseptic necrosis (p = 0.005). Temporal clustering of acute chest syndrome episodes frequently heralds the onset of SCLD. The pulmonary arterial bed, which has low oxygen tension and low pressure in a slow-flow system, is ideally suited to facilitate the polymerization of sickle hemoglobin, causing endothelial damage and culminating in an obstructive arteriolar vasculopathy. Identification of the significant risk factors predictive of SCLD can lead to early diagnosis of the disease; this is the only hope for effective intervention therapy.     

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 complications in adult sickle cell disease

Sickle cell disease is an autosomal genetic condition which represents the most frequent genetic disease in ?le-de-France and Caribbean islands. The main clinical manifestations can be divided into infectious disease, hemolytic anemia and vaso-occlusive events. Pulmonary complications represent 20 to 30% of mortality due to sickle cell and can be divided into acute and chronic events. Acute chest syndrome (ACS) is an acute lung injury often preceded by a vaso-occlusive crisis and triggered by different factors including: hypoventilation, pulmonary infectious disease and vascular occlusions. These occlusions can be secondary to fat embolism, thrombosis or sickling. Treatment is mainly supportive combining oxygen supplementation adequate hydration analgesia and sedation. Exchange transfusion may be indicated in severe forms of ACS, characterized by a right ventricular dysfunction and acute respiratory failure. Pulmonary hypertension is the most serious chronic complication. Its frequency is estimated at 6% in adult patients and is more often described in patients with venous ulcers and higher levels of chronic hemolysis. Prognosis is poor with 12.5% of patients dying in the first two years following diagnosis irrespective of the actual pulmonary artery pressure level. There are currently limited data on the effects of any treatment modality. Other respiratory complications such as sleep disorders and nocturnal hypoxemia, infiltrative lung disease and exertional dyspnea are described and should be considered.