Infarction In Sickle Cell Disease Research Articles

Silent infarction in sickle cell disease is associated with brain volume loss in excess of infarct volume.

Sickle cell disease (SCD) increases cerebral infarct risk, but reported effects on brain volume have varied. More detailed information using larger cohorts and contemporary methods could motivate the use of longitudinal brain volume assessment in SCD as an automated marker of disease stability or future progression. The purpose of this study was to rigorously evaluate whether children and young adults with SCD have reduced gray matter volume (GMV) and white matter volume (WMV) compared to healthy controls using high-resolution MRI. We tested the hypotheses that (i) elevated CBF, a marker of cerebral hemodynamic compensation in SCD, is associated with global and regional brain atrophy, and (ii) silent cerebral infarct burden is associated with brain atrophy in excess of infarct volume. Healthy controls (n = 49) and SCD participants without overt stroke (n = 88) aged 7-32 years completed 3 T brain MRI; pseudocontinuous arterial spin labeling measured CBF. Multivariable linear regressions assessed associations of independent variables with GMV, WMV, and volumes of cortical/subcortical regions. Reduced hemoglobin was associated with reductions in both GMV (p = 0.032) and WMV (p = 0.005); reduced arterial oxygen content (CaO2) was also associated with reductions in GMV (p = 0.035) and WMV (p = 0.006). Elevated gray matter CBF was associated with reduced WMV (p = 0.018). Infarct burden was associated with reductions in WMV 30-fold greater than the infarct volume itself (p = 0.005). Increased GM CBF correlated with volumetric reductions of the insula and left and right caudate nuclei (p = 0.017, 0.017, 0.036, respectively). Infarct burden was associated with reduced left and right nucleus accumbens, right thalamus, and anterior corpus callosum volumes (p = 0.002, 0.002, 0.009, 0.002, respectively). We demonstrate that anemia and decreased CaO2 are associated with reductions in GMV and WMV in SCD. Increased CBF and infarct burden were also associated with reduced volume in subcortical structures. Global WMV deficits associated with infarct burden far exceed infarct volume itself. Hemodynamic compensation via increased cerebral blood flow in SCD seems inadequate to prevent brain volume loss. Our work highlights that silent cerebral infarcts are just a portion of the brain injury that occurs in SCD; brain volume is another potential biomarker of brain injury in SCD.

Abstract WP260: The Response Of Annexin A1 In Astrocyte Activation And White Matter Injury- A New Target For Stroke In Sickle Cell Disease

Introduction: Ischemic stroke is common in sickle cell disease (SCD). White matter injuries, incorporated into silent cerebral infarcts, are major risk factors of stroke in SCD. The pathogenesis of cerebral infarction in SCD is not known. Induced thrombogenesis may cause impaired astrocyte that stimulates demyelination leading to white matter injury. Annexin A1 (Anxa1) can regulate astrocyte function by inhibiting intracellular phospholipase A2 (PLA2). We hypothesized that astrocyte activation during thrombogenic events promotes white matter injury in SCD. We tested astrocyte dysfunction and white matter injury in a clinically relevant mouse model of SCD. Methods: Cerebral Infarctions induced by de novo thrombogenesis were identified by TTC staining in transgenic sickle (SS) and control (AA) mice with human sickle and normal hemoglobin respectively. Cerebral microvessels and astrocytes were isolated from SS and AA mice. Elisa assays were used to measure thrombin, PLA2 and Anxa1. Immunofluorescence staining was performed to determine astrocyte activation and demyelination. Results: Thrombogenesis within cerebral microvessels was elevated by ~2-fold (n=5, p<0.05), and cerebral infarction became prevalent in SS mice compared to AA mice (n=7, p<0.001). The infarcted brain tissue from SS mice showed neuronal cell death, whereas the brain tissue from the AA mice appeared normal. The SS mice had increased glial fibrillary acid protein positive (GFAP + ) activated astrocytes with significant increase in PLA2 accumulation. Relative abundance of non-phosphorylated neurofilament H (SMI32) and myelin basic protein (MBP) (SMI32/MBP), indicating white matter injury, was substantially induced in the SS compared to the AA. Expression of Anxa1 reduced significantly in plasma as well as within astrocytes’ end feet attached to the isolated cerebral microvessels of the SS mice. Recombinant Anxa1 prophylaxis to SS mice reduced the GFAP + astrocytes, PLA2 accumulation, demyelination and infarct score (n=6, p<0.01) compared to SS mice treated with vehicle. Conclusion: White matter injury in SS mice is associated with astrocyte dysfunction and lack of Anxa1, which may be developed as potential therapeutic targets to prevent and/or treat stroke in SCD.

Safety of 3 Tesla Magnetic Resonance Imaging in Patients with Sickle Cell Disease.

Sickle cell disease (SCD) is a well-characterized hemoglobinopathy affecting more than 20 million individuals worldwide and carries an increased risk of cerebral vasculopathy, cerebral infarct, and stroke. As mechanisms of cerebral infarction in SCD are partly attributable to microvascular vaso-occlusive crises, manifesting as altered cerebral blood flow and associated impaired oxygen delivery, magnetic resonance imaging (MRI) methods that can quickly provide a comprehensive perspective on structural and functional disease status, without exogenous contrast administration or ionizing radiation, have emerged as crucial clinical tools for surveillance. However, early ex vivo MRI work in suspended erythrocytes containing hemoglobin S at 0.35 Tesla (T) suggested that sickled erythrocytes can orient preferentially in the presence of an external magnetic field, and as such, it was suggested that MRI exams in sickle cell hemoglobinopathy could induce vaso-occlusion. While this observation has generally not impacted clinical imaging in individuals with SCD, it has led to resistance for some sickle cell studies within the engineering community among some imaging scientists as this early observation has never been rigorously shown to be unconcerning. Here, we performed MRI at the clinical field strength of 3 T in 172 patients with SCD, which included standard anatomical and angiographic assessments together with gold standard diffusion-weighted imaging (DWI; spatial resolution = 1.8 × 1.8 × 4 mm; b-value = 1000 s/mm2) for acute infarct assessment (performed approximately 20 min after patient introduction to the field isocenter). The presence of vasculopathy, as well as chronic and acute infarcts, was evaluated by two independent board-certified radiologists using standard clinical criteria. In these patients (52.3% female; mean age = 19.6 years; age range = 6–44 years), hematocrit (mean = 25.8%; range = 15–36%), hemoglobin phenotype (87.8% HbSS variant), presence of silent infarct (44.2%), and overt chronic infarct (13.4%) were consistent with a typical SCD population; however, no participants exhibited evidence of acute infarction. These findings are consistent with 3 T MRI not inducing acute infarction or vaso-occlusion in individuals with SCD and suggest that earlier low-field ex vivo work of erythrocytes in suspension is not a sufficient cause to discourage MRI scans in patients with SCD.

Regional oxygen extraction predicts border zone vulnerability to stroke in sickle cell disease.

To determine mechanisms underlying regional vulnerability to infarction in sickle cell disease (SCD) by measuring voxel-wise cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen utilization (CMRO2) in children with SCD. Participants underwent brain MRIs to measure voxel-based CBF, OEF, and CMRO2. An infarct heat map was created from an independent pediatric SCD cohort with silent infarcts and compared to prospectively obtained OEF maps. Fifty-six participants, 36 children with SCD and 20 controls, completed the study evaluation. Whole-brain CBF (99.2 vs 66.3 mL/100 g/min, p < 0.001), OEF (42.7% vs 28.8%, p < 0.001), and CMRO2 (3.7 vs 2.5 mL/100 g/min, p < 0.001) were higher in the SCD cohort compared to controls. A region of peak OEF was identified in the deep white matter in the SCD cohort, delineated by a ratio map of average SCD to control OEF voxels. CMRO2 in this region, which encompassed the CBF nadir, was low relative to all white matter (p < 0.001). Furthermore, this peak OEF region colocalized with regions of greatest infarct density derived from an independent SCD cohort. Elevated OEF in the deep white matter identifies a signature of metabolically stressed brain tissue at increased stroke risk in pediatric patients with SCD. We propose that border zone physiology, exacerbated by chronic anemic hypoxia, explains the high risk in this region.

Association of Annexin A5 Resistance with Silent Infarct in Sickle Cell Disease

Background: In sickle cell disease (SCD) abnormally shaped RBCs interact with white blood cells and the endothelium, leading to a vasculopathy and thrombotic/ prothrombotic complications such as stroke and pulmonary hypertension. About 10 % of patients with a thrombotic event in the general population will have the presence of an antiphospholipid (aPL) antibody (Andreoli et al. 2013). One proposed mechanism for the thrombophilic nature of aPL antibodies is the disruption of annexin A5. Annexin A5 is a potent anticoagulant protein that has an affinity to phospholipids. In the presence of aPL antibodies, annexin A5 is unable to form its crystallized anticoagulant shield (annexin A5 resistance). There is a paucity of data which assesses the association of aPL antibodies with vasculopathic complications of SCD, and there have been no studies investigating the annexin A5 resistance assay (A5R). We designed a pilot study assessing aPL antibody levels and A5R in a pediatric sickle cell population.Methods: Patients with a history of stroke, abnormal transcranial doppler (TCD) and elevated TR gradient by echocardiography (>25mm of Hg) were eligible. A5R, lupus anticoagulant- DRRVT, anti β2GP1, anti phosphatidylserine and anti cardiolipin antibody (IgG, IgA, IgM) assays were performed on samples obtained prospectively when patients were at a steady state (at least 4 weeks after an acute event). A5R measures coagulation times in the presence and absence of annexin A5. Resistance to the anticoagulant effects of annexin is expressed as a reduction in this ratio (Rand et al. 2004). Statistical analysis assessed multiple variables including age, gender, hemoglobin, reticulocyte count, LDH, hydroxyurea therapy, transfusion therapy, elevated TR gradient, stroke and silent stroke. Univariate analysis and multivariate logistic regression was performed with abnormal annexin A5 as the outcome variable.Results:There were a total of 39 patients: 12 patients with a history of stroke, 6 with an elevated TCD velocity and 15 patients with an elevated TR gradient. Of the 27 patients that did not have a stroke, 25 had a screening MRI in the prior year, and 9 of these patients had silent infarcts. Only 1 of 39 patients had elevated anticardiolipin IgG antibodies and 1 had an abnormal lupus coagulant (DRVVT). In contrast, 5/39 patients (12.8%) had low or abnormal annexin A5 resistance, 7/39 (18%) were in the borderline range and 27/39 (69%) were normal. This frequency of abnormality was unexpected in the antiphospolipid antibody and lupus anticoagulant negative population. None of the patients, except the one with the positive lupus anticoagulant, developed any thrombotic events in 3.5 years of follow up. None of the patients with overt stroke or abnormal TCDs had an abnormal A5R. Multivariate logistic regression analyses showed statistically significant association of hemoglobin (p= 0.037, OR 0.25, CI 0.07-0.92)), age (p =0.047, OR 1.43, CI 1.01-2.04) and silent infarct (p =0.015, OR 28.5, CI 1.9-420.5) with abnormal annexin A5 resistance. A multivariate analysis using linear regression with annexin A5 resistance as a continuous outcome variable (Table 1), showed persistence of the significant association of silent infarcts (p =0.037).Conclusion: We report an association between annexin A5 resistance and low hemoglobin, older age and presence of silent infarct in a subgroup of SCD patients. Prevalence of abnormal aPL antibody assays and lupus anticoagulant was strikingly low in this cohort. A potential role for perturbed annexin A5 resistance in the pathophysiology of silent infarction in SCD will need to be evaluated further in carefully designed prospective studies and may be a novel therapeutic target.Table 1Hemoglobin, Age and Silent Stroke are Associated with Abnormal Annexin A5 ResistanceCharacteristicOdds RatioOdds Ratio Confidence Intervalp-valueHemoglobin*0.250.07-0.920.037Reticulocyte count0.770.54-1.080.13LDH1.000.99-1.000.51Age*1.431.01-2.040.047Monocyte count1.001.00-1.000.34Silent infarct*28.51.9-420.50.015Stroke0.470.05-4.880.53Elevated TR gradient0.340.03-3.490.36Gender0.470.05-4.880.53Allosensitization0.560.05-5.860.63HU vs no treatment0.460.03-6.930.58Transfusion vs no treatment0.180.01-4.260.29 DisclosuresNo relevant conflicts of interest to declare.

Breakthrough: new guidance for silent cerebral ischemia and infarction in sickle cell disease.

Silent cerebral infarction (SCI) is a highly prevalent and morbid condition in sickle cell disease (SCD). SCI can occur beginning in the first year of life and becomes more common with increasing age. Potentially modifiable risk factors for SCI include anemia and blood pressure. Headache does not appear to be associated with SCI, so neurologically normal children with headache do not necessarily warrant screening MRI for SCI. SCI does affect cognition, but biological determinants of cognition are not more important than socioeconomic factors. The recent identification of acute silent cerebral ischemic events indicates that the total burden of ischemic injury to the brain in SCD is far greater than previously realized. Acute anemic events appear to increase the risk of acute silent cerebral ischemic events and SCI dramatically. The medical management of SCI is not yet defined, but documentation of the presence of SCI may qualify affected individuals for special resources because comprehensive interventions are needed to optimize patients' academic and vocational outcomes.

Sterile subperiosteal fluid collections accompanying orbital wall infarction in sickle-cell disease

Infarction of the orbital wall is an uncommon manifestation of sickle cell disease (SCD) that may mimic an infectious process. We report a patient with two separate orbital infarctions with different presenting symptoms involving different bones. Radiologic-guided sampling of a periosteal fluid collection in the first episode showed likely sterile inflammatory exudates. This case highlights the range of findings in orbital wall infarction in SCD as well as helpful clinical and imaging entities that may differentiate infarction from infection, allowing early diagnosis and appropriate management.

Neuropathy, neuropathic pain, and sickle cell disease

Neuropathy, neuropathic pain, and sickle cell disease

Dilemma in Differentiating between Acute Osteomyelitis and Bone Infarction in Children with Sickle Cell Disease: The Role of Ultrasound

BackgroundDistinguishing between acute presentations of osteomyelitis (OM) and vaso-occlusive crisis (VOC) bone infarction in children with sickle cell disease (SCD) remains challenging for clinicians, particularly in culture-negative cases. We examined the combined role of ultrasound scan (USS), C - reactive protein and White blood counts (WCC) in aiding early diagnosis in children with SCD presenting acutely with non-specific symptoms such as bone pain, fever or swelling which are common in acute osteomyelitis or VOC.MethodsWe reviewed the records of all children with SCD who were discharged from our department from October 2003 to December 2010 with a diagnosis of osteomyelitis based on clinical features and the results of radiological and laboratory investigations. A case control group with VOC who were investigated for OM were identified over the same period.ResultsIn the osteomyelitis group, USS finding of periosteal elevation and/or fluid collection was reported in 76% cases with the first scan (day 0–6). Overall 84% were diagnosed with USS (initial +repeat). 16% had negative USS. With VOC group, USS showed no evidence of fluid collection in 53/58 admissions (91%), none of the repeated USS showed any fluid collection. Mean C-reactive protein (CRP), and white cell count (WCC) were significantly higher in the OM.ConclusionThe use of Ultrasound in combination with CRP and WCC is a reliable, cost-effective diagnostic tool for differentiating osteomyelitis from VOC bone infarction in SCD. A repeat ultrasound and/or magnetic resonance imaging (MRI) scan may be is necessary to confirm the diagnosis.

Myocardial Infarction in Sickle Cell Disease: Use of Translational Imaging to Diagnose an Under-Recognized Problem

Sickle cell disease (SCD) is an inherited disorder in which microvascular occlusion causes complications across multiple organ systems. The precise incidence of myocardial ischemia and infarction (MI), potentially under-recognized microvascular disease-related complications, remains unknown. The absence of typical atherosclerotic lesions seen in other patients with MI suggests a microvascular mechanism of myocardial injury. Cardiac magnetic resonance (CMR) can demonstrate microvascular disease, making it an appealing modality to assess symptomatic SCD patients. We demonstrate in several dramatic instances how CMR is uniquely able to depict cardiac microvascular obstruction in patients with SCD and chest pain, without which the possibility of myocardial injury would almost certainly be otherwise neglected. Much remains unknown regarding ischemic heart disease in patients with SCD including prevalence, detection, and management. Further work to define evaluation and management algorithms for chest pain in SCD and to develop risk assessment tools may reduce sudden cardiac death in this population.

Etiology and Management of Splenic Infarction and Splenic Vein Thrombosis: Unusual Causes of Abdominal Pain in Sickle Cell Trait Patient

AbstractAbstract 4775Abdominal pain is a common complaint among all ages of patients. Splenic infarction and splenic vein thrombosis are rare causes of abdominal pain, usually presenting as left-sided abdominal pain associated with fever, nausea or vomiting, and elevated white blood cell count. CT scan is currently the preferred diagnostic test. Once the diagnosis is identified, the etiology of splenic infarction and/or splenic vein thrombosis should be elicited.Retrospective chart review was conducted in all the patients admitted to our hospital from 2000 till now. Four cases of splenic infarction and/or splenic vein thrombosis were identified (4 males, average age of 45 years, range from 38 to 52 years). Case 1, a 45-year-old male with sickle cell trait (HbS of 38.7%), presented with left upper quadrant pain after 5-hour flight and alcohol binge prior to flight. CT showed splenic infarct and splenic vein thrombosis. Patient received aggressive hydration, abdominal pain resolved and was discharged home. Case 2, a 52-year-old male with renal cell carcinoma, presented with generalized abdominal pain. CT showed splenic infarct. Patient was treated with Coumadin, and routinely followed-up at Oncology clinic. Case 3, a 38-year old male with alcohol abuse and chronic pancreatitis, presented with recurrent abdominal pain and hypersplenism. CT showed splenic vein thrombosis, and the patient underwent splenectomy. Case 4, a 45-year-old male with acute pancreatitis, presented with epigastric pain. CT showed splenic vein thrombosis, and the patient was treated with Coumadin.It is important to reveal the underlying causes for splenic infarction and/or splenic vein thrombosis. Splenic infarction can occur in a variety of settings, including hemoglobinopathy (especially sickle cell disease), hypercoagulable state, embolic disease, malignancy and myeloproliferative disorders. Pancreatitis and pancreatic cancer are the most common causes of splenic vein thrombosis. In general, splenic infarction and/or splenic vein thrombosis can be managed safely with medical treatment, including hydration, oxygenation and pain management. Coumadin can be considered in cancer patients with splenic infarction and in patients with splenic vein thrombosis. Splenectomy is indicated in patients with hypersplenism, splenic sequestration crisis, splenic abscess, splenic rupture, and massive splenic infarction.Splenic infarction in sickle cell disease is usually small and repetitive, leading ultimately to autosplenectomy. Splenic infarction in sickle cell trait is rare. High altitude, vigorous exercise, airplane flight, coexistence with thalassemia or hereditary spherocytosis or severe pyruvate kinase deficiency, can precipitate infarction. Interestingly in our first case, the patient with sickle cell trait developed splenic infarction and non-occlusive thrombus in the distal splenic vein after 5-hour flight. It is possible that the hypoxia associated with the commercial flight caused conformational changes in sickle cells, leading to red blood cells sluggish in the splenic red pulp, and eventually leading to splenic infarction. The alcohol binge resulted in dehydration and hemostasis, leading to splenic vein thrombosis, further perpetuating the vicious cycle. Therefore, we recommend adequate hydration and in-flight oxygen supplementation for sickle cell trait patients taking airplane flight. Further studies need to be done to confirm our hypothesis. Disclosures:No relevant conflicts of interest to declare.

Erythrocytapheresis in the prevention of recurrent myocardial infarction in sickle cell disease

Erythrocytapheresis in the prevention of recurrent myocardial infarction in sickle cell disease

Orbital Infarction in Sickle Cell Disease

To determine the role of hematological and genetic factors in the development of orbital infarction in sickle cell disease. Retrospective, noncomparative case series. Fourteen sickle cell disease patients were diagnosed with orbital infarction during a vaso-occlusive crisis. Clinical and radiological findings were reviewed retrospectively. Sickle cell disease patients without orbital infarction were recruited as controls after matching for disease severity. Sickle haplotypes were determined for all patients. Differences between groups were evaluated statistically. Patients with orbital infarction in sickle cell disease presented with acute periorbital pain and swelling with or without proptosis, ophthalmoplegia, and visual impairment during a vaso-occlusive crisis. Radiological findings included orbital soft tissue swelling (100%), hematoma (orbital, 36%; intracranial, 21%), and abnormal bone marrow intensities. Severity of orbital involvement was unrelated to that of the systemic disease (Pearson correlation coefficient, -0.1567). Affected patients predominantly had the Benin haplotype (P < .00782). Orbital infarction is a potential threat to vision in sickle cell disease patients. Magnetic resonance imaging is more specific than computed tomography or nuclear scintigraphy in the evaluation of orbital changes. The degree of severity of the orbital manifestations appears unrelated to the severity of sickle cell disease. Patients with the Benin haplotype are more likely to develop orbital infarction during vaso-occlusive crises.

Acute Myocardial Infarction in Sickle Cell Disease

Myocardial infarction in young adults is, in practice, a diagnosis of exclusion. Given the fact that most of the patients with sickle cell disease are young and have predisposition to painful crisis, they are often overlooked for myocardial infarction. These patients often have few or no traditional risk factors for coronary artery disease, and risk stratification tools such as the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) models place these patients at low risk. Nonspecific changes on electrocardiogram are of little diagnostic value. Myocardial infarction is very often a missed diagnosis in patients with sickle cell disease. Diagnostic criteria, potential mechanisms, and management for acute myocardial infarction in patients with sickle cell disease are discussed.

Acute chest pain in a young woman with a chronic illness

Case of the monthAcute chest pain in a young woman with a chronic illnessD S KUMAR, R P YADAVALI, L A CONCEPCION and H ANIQD S KUMARDepartment of Radiology, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, UKSearch for more papers by this author, R P YADAVALIDepartment of Radiology, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, UKSearch for more papers by this author, L A CONCEPCIONDepartment of Radiology, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, UKSearch for more papers by this author and H ANIQDepartment of Radiology, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, UKSearch for more papers by this authorPublished Online:5 Mar 2014https://doi.org/10.1259/bjr/60270972SectionsPDF/EPUBFull Text ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail About References 1 Siddiqui AK, Ahmed S. Pulmonary manifestations of sickle cell disease. Postgrad Med J 2003;79:384–90. Crossref Medline ISI, Google Scholar2 Lonergan GJ, Cline DB, Abbondanzo SL. Sickle cell anemia. Radiographics 2001;21:971–94. Crossref Medline ISI, Google Scholar3 Stuart MJ, Setty BN. Acute chest syndrome of sickle cell disease: new light on an old problem. Curr Opin Hematol 2001;8:111–22. Crossref Medline ISI, Google Scholar4 Minter KR, Gladwin MT. Pulmonary complications of sickle cell anemia. A need for increased recognition, treatment, and research. Am J Respir Crit Care Med 2001;164:2016–19. Crossref Medline ISI, Google Scholar5 Leong CS, Stark P. Thoracic manifestations of sickle cell disease. J Thorac Imaging 1998;13:128–34. Crossref Medline ISI, Google Scholar6 Mansi IA, Rosner F. Myocardial infarction in sickle cell disease. J Natl Med Assoc 2002;94:448–52. Medline ISI, Google Scholar7 Stoker DJ, Saifuddin A. Myeloproliferative and similar disorders. In: Grainger RG, Allison DJ, Adam A, Dixon AK, editors. Grainger & Allison's diagnostic radiology. Edinburgh, UK: Churchill Livingstone, 2004: 1904–7. Google Scholar8 Cobby M, Watt I. Tumours and tumour-like conditions of bone. In: Sutton D, editor. Textbook of radiology and imaging. Edinburgh, UK: Churchill Livingstone, 2003: 1287–1320. Google Scholar Previous article Next article FiguresReferencesRelatedDetailsCited byMultidetector CT Scan in the Evaluation of Chest Pain of Nontraumatic Musculoskeletal OriginThoracic Surgery Clinics, Vol. 20, No. 1Multidetector CT Scan in the Evaluation of Chest Pain of Nontraumatic Musculoskeletal OriginRadiologic Clinics of North America, Vol. 48, No. 1Current World LiteratureCurrent Opinion in Supportive & Palliative Care, Vol. 3, No. 2 Volume 81, Issue 963March 2008Pages: 169-e99 © The British Institute of Radiology History RevisedJuly 12,2006ReceivedMay 26,2006AcceptedJuly 31,2006Published onlineMarch 05,2014 Metrics Download PDF

Orbital infarction in sickle cell disease: A clinicogenetic study from Oman

Background: Orbital infarction is an unusual complication of a vaso-occlusive crisis (VOC) in sickle cell disease (SCD). The infarctive process produces an inflammatory response that can cause orbital compression syndrome. SCD is widely prevalent in Oman, providing a unique opportunity for identifying the influence of different ethnic backgrounds and sickle haplotypes in the etiopathogenesis of orbital infarction in SCD. Aim: To determine the role and significance of hematologic and genetic factors in Omani SCD patients with orbital infarction.

Myocardial infarction in sickle-cell disease

A 50-year-old woman was admitted to our hospital in December, 2005, with a 5 h history of central chest pain of sudden onset. She described dull pain across her chest with radiation to the right arm accompanied by nausea and vomiting. The pain was worse on deep inspiration but not associated with dyspnoea, and it failed to improve after glyceryl trinitrate. She had a history of homozygous sickle-cell disease with frequent painful episodes; she managed most of these episodes at home with diclofenac and dihydrocodeine phosphate, although intermittently needed exchange transfusion.

Positron emission tomography scans for distinguishing between osteomyelitis and infarction in sickle cell disease

In a recently published review on bone involvement in sickle cell disease Almeida and Roberts (2005) reported that differentiation between bone infarction and osteomyelitis in sickle cell patients remains a diagnostic problem. Differentiation is essential because of the risk of the under-treatment of osteomyelitis. The clinical features of vaso-occlusive crisis are often comparable to osteomyelitis. In both vaso-occlusive crises and osteomyelitis, patients complain of pain and tenderness on palpation of the involved bone. A periosteal reaction resulting in swelling and erythema can occur in both conditions. Differentiation is usually not possible solely on clinical signs. When osteomyelitis is suspected, imaging of the affected area could help to support the diagnosis. Nuclear imaging, such as bone scintigraphy with 99mTc-labelled methylene diphosphonate, is highly sensitive for many active benign and malignant bone disorders. Therefore, it plays an important role in the evaluation of osteomyelitis, especially in acute osteomyelitis. In chronic osteomyelitis, the uptake of bone-seeking tracers is rather poor and non-specific. Radiolabelled white blood cells are commonly used to visualise infection or inflammation. In sickle cell disease, however, it has been shown that leucocyte scans cannot reliably discriminate between sickle cell vaso-occlusive crises and osteomyelitis. Magnetic resonance imaging (MRI) can display abnormal periosteal swelling but also fails to discriminate between infarction and infection. In a recent effort to discriminate between vaso-occlusive crises and osteomyelitis of the mandible in a known sickle cell patient, a three-phase bone scan was performed. The patient's complaints were pain in the mandibular angle with tenderness on palpation on the left side and a numb left lower lip for more than 3 weeks. These clinical signs were highly suspicious of a vaso-occlusive crisis or osteomyelitis. The bone scan showed slightly increased uptake in the left mandible area and some inhomogeneous uptake in the skull. A leucocyte scan could not be completed because the in vitro separation procedure of leucocytes from red blood cells and platelets before labelling from the patient's blood sample was not successful. Since the complaints of the patient did not resolve, further attempts were made to determine the nature of his complaints. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was used to establish the presence of inflammation. In areas of inflammation or infection, a high glucose metabolism is present, which results in an accumulation of the glucose analogue FDG. The FDG-PET showed a remarkably high intensive hot spot in the left mandible and no other hot spots in the rest of the skull (Fig 1). The intensity of this spot did not correspond to the intensity of the spot on the bone scan. To verify the finding of the FDG-PET scan a second PET scan was performed using 18F-NaF. This type of PET scan displays bone remodelling processes comparable to bone scans, but with a higher spatial resolution. The 18F-NaF is incorporated in hydroxyapatite of the bone and its accumulation is dependent on the regional blood flow and the osteoblastic activity (Cook & Fogelman, 2002). The 18F-NaF PET scan showed multiple inhomogeneous spots in the skull, mainly in concurrence with the bone scan. An intense hot spot was seen in the left mandible, the intensity of which was comparable to the 18F-FDG PET scan. The findings on the PET scans supported the diagnosis of osteomyelitis. One week after with the commencement of antibiotics an abscess developed at the painful site of the mandible. Various scan results of the patient. (A) 99mTc bone scan with increased uptake at the mandible. (B) 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan showing a single hot spot at the left mandible. Frontal (C) and lateral (D) views of a NaF PET scan showing multiple areas of infarction/remodelling in the skull and one intense hot spot in the left mandible corresponding to the single hot spot in FDG-PET scan, as depicted in B. In this particular case, PET scans helped to discriminate between infarction and inflammation or infection. It is therefore suggested that, when a distinction between infarction and infection is required and bone scintigraphy or a leucocyte scan is not conclusive, FDG-PET imaging could be considered.

Acute myocardial infarction in sickle cell disease: a possible complication of hydroxyurea treatment

We describe a 28-year-old man treated with hydroxyurea for sickle cell anemia, who was admitted to the University Hospital with an acute myocardial infarction. The patient had evolved high hematocrit values during his long-term hydroxyurea treatment, suggesting a correlation between a possible increment in blood viscosity and the coronary occlusion without previous lesions. Indeed, several studies associate vasocclusive episodes and severe clinical course with high viscosity. Although hydroxyurea is considered an effective therapeutic option for these patients, care should be taken to monitor hematocrit levels and possible complications. Hematocrit and hemoglobin values of above 30% and 10.5 g/dl in SS patients on hydroxyurea therapy should be avoided or closely monitored.

Differentiating osteomyelitis from bone infarction in sickle cell disease.

This brief review discusses one possible approach to evaluating the sickle cell patient with bone pain. The major differential diagnoses include osteomyelitis and bone infarction. Based on previous studies, we provide an approach to assessing and treating patients with the possible diagnosis of osteomyelitis. An algorithm has been provided, which emphasizes the importance of the initial history and physical examination. Specific radiographic studies are recommended to aid in making the initial assessment and to determine whether the patient has an infarct or osteomyelitis. Differentiating osteomyelitis from infarction in sickle cell patients remains a challenge for the pediatrician. This algorithm can be used as a guide for physicians who evaluate such patients in the acute care setting.