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.

Renal medullary carcinoma in a young mixed-race man in Japan.

Renal medullary carcinoma (RMC) is a rare and aggressive cancer associated with the sickle cell trait. The diagnosis of RMC depends on recognition of its histologic features and immunohistochemical deficiency of INI1, but correct diagnosis is sometimes difficult, especially if a patient's information on race, past, and family medical history is unclear. At present, this is the first report on RMC in Japan.

Nutcracker Syndrome and Sickle Cell Trait: A Perfect Storm for Hematuria.

We describe the case of a 27-year-old woman with a history of sickle cell trait (SCT) who presented with several months of hematuria and was found to have nutcracker syndrome (NCS). While SCT is a common cause of hematuria resulting from renal papillary necrosis, our patient had concomitant abdominal pain and anemia, prompting further evaluation and the subsequent diagnosis of NCS. Interestingly, the anoxia in the left renal vein from NCS predisposes patients with SCT to sickling. Our case highlights key clinical features of both NCS and SCT and the relationship between the two disease processes.

Prevalence of transcranial Doppler abnormalities in Nigerian children with sickle cell disease.

Transcranial Doppler (TCD) ultrasonography helps to identify children with sickle cell disease (SCD) who are at an increased risk of stroke,making primary stroke prevention a reality. A cross-sectional study of145 Nigerian children aged ≥3 years with SCD was carried out to describe the pattern of cerebral blood flow (CBF) abnormalities. The mean time-averaged mean velocity (TAMV) was 152 ±27.0 cm/sec and122 ±22.0 cm/sec in Hb SS and Hb S1C group, respectively. Abnormal velocities were recorded in six (4.7%) of the Hb SS patients and none of the Hb S1C while conditional risk (CR) velocities were recorded in 19.7% of Hb SS (low conditional 11.0%, high conditional 8.7%) and low conditional in 5.6% of Hb S1C cases. Cerebral flow velocities showed a negative correlation with age and hematocrit. Compared with African-American children, Nigerian children with Hb SS disease have a considerably higher prevalence of CR velocities.

Hemolysis Following Intraoperative Cell Salvage Replacement in a Scoliosis Patient With Sickle Cell Trait: A Case Report.

MINI: Intraoperative cell salvage (ICS) is used to reduce blood loss in scoliosis spinal fusion. We report one case of hemolysis induced acute renal failure following ICS. This is the first reported case of acute renal failure associated with hemolysis following ICS in a scoliosis patient with sickle cell trait. STUDY DESIGN: Case report. OBJECTIVE: To describe a novel presentation of acute renal failure associated with hemolysis after intraoperative cell salvage (ICS) in a neuromuscular scoliosis patient with sickle cell trait (SCT). SUMMARY OF BACKGROUND DATA: Hemolysis-associated acute renal failure after ICS in patients with SCT has not been previously reported. Sickle cell disease is regarded as a relative contraindication for ICS due to the risk of red blood cell sickling in the hypoxic cell saver reservoir. A previous case series demonstrated successful ICS reinfusion after elective caesarean section in two patients with SCT. However, a decision to not reinfuse ICS collected blood due to increased sickling after blood processing was reported in general surgery. METHODS: A 14-year-old female with Group I neuromuscular scoliosis underwent a navigated T3-S1posterior spinal instrumentation fusion. Three hundred milliliters of blood collected by ICS was reinfused intraoperatively along with two units of packed red blood cells. RESULTS: Postoperatively, the patient had delayed emergence from the general anesthetic and gross hematuria was observed in the urinary catheter bag. The patient was transferred to the intensive care unit and was treated successfully for hemolysis-induced renal failure. CONCLUSION: Given the potential seriousness of hemolysis-associated acute renal failure associated with ICS, we recommend against the use of ICS in patients with SCT. LEVEL OF EVIDENCE: 5.

Acute myocardial infarction in a patient with sickle cell trait.

Presently described is the rare complication of sickle cell trait (HbAS) with acute inferior myocardial infarction in a young adult patient. Angiogram revealed microemboli in the distal thin segment of the circumflex (Cx) artery. Anticoagulant and anti-aggregant therapies were initiated to restore Cx artery flow. HbAS was detected as an underlying pathology. ST segments returned to the isoelectric line and the patient became asymptomatic.

Unusual presentation of anaerobic osteomyelitis.

Acute hematogenous osteomyelitis was detected in a 23-year-old sickle-cell patient after standard radiographs of the right femur showed gas within the medullary cavity. Three anaerobic organisms were cultured from surgically aspirated materials, but no source of infection was found. After surgical drainage and six weeks of intravenous clindamycin therapy, there was clinical improvement and radiographic resolution of the gas formation.

Spectral pulsed Doppler sonography of renal vascular resistance in sickle cell disease: clinical implications.

The major complications in sickle cell disease (SCD) are microcirculation lesions and impairment of renal function. The aim of this study was the evaluation of renal vascular resistance by means of spectral pulsed Doppler sonography and its relationships with haematological and clinical features in patients with SCD. 40 patients with SCD (mean age 22.4 +/- 7.0) and 14 age and sex matched healthy subjects (mean age 25.7 +/- 9.5) were included into the study. Spectral Doppler sonography of main renal, segmental and interlobar arteries were performed on both kidneys in all patients and controls. Peak systolic, end diastolic and mean velocities through the entire cardiac cycle were obtained, with calculation of the resistive (RI) and pulsatility (PI) indices. All the patients were investigated in stable state conditions and had not been transfused within a month before investigation. Patients were followed for up to 6 months. Patients with SCD had higher values of RIs and PIs than control subjects (p < 0.0001, p < 0.0001, respectively). Patients with high value of RIs (RI > 0.70) had more pronounced disturbances of blood parameters (all p < 0.05), than patients with normal RIs (RI < 0.70). Significant positive correlation existed between RIs and ISC number, MCHC level (r = 0.52, p < 0.001 and r = 0.42, p < 0.01), while RBC count and Hb level correlated inversely with RIs (r = -0.39, p < 0.01 and r = -0.42, p < 0.01). During follow-up, nine patients (33.3%) with high RIs and only one patient (5.5%) with normal RI developed painful crises. In conclusion, renal vascular resistance, assessed by Doppler sonography was raised in SCD patients as compared with age matched apparently healthy persons. These changes were more pronounced in those with more severe manifestations of disease and correlated with haematological and clinical features of sickle cell disease.

Pseudomoyamoya in sickle cell anemia.

Sickle cell (drepanocytic) anemia is a hereditary blood disease occurring very rarely in Mexico. A 13-year-old Mexican boy with sickle cell anemia eventually died of a cerebrovascular accident of the brain stem, as shown by computerized tomography (CT). A characteristic moyamoya-like angiographic pattern was demonstrated on bilateral carotid and left vertebral arteriograms. Moyamoya disease has no known etiology, but the characteristic angiographic features of moyamoya have been observed in conjunction with some other disease of known origin (including sickle cell anemia). It is therefore my belief that these latter cases should be referred to as pseudomoyamoya and not true moyamoya.

Craniofacial features of patients with sickle cell anemia and sickle cell trait.

OBJECTIVE: To identify the craniofacial characteristics of patients with sickle cell trait (SCT) and sickle cell anemia (SCA) and to compare these measurements with those of nonaffected subjects. MATERIALS AND METHODS: Clinically normal patients and those with SCT and SCA were evaluated in this study. The patients were divided into three groups: normal (control), SCA, and SCT (n  =  with 15 in each group). Inclusion criteria were SCA or SCT verified by laboratory methods and no treatment with fixed orthodontics or facial orthopedics. Lateral cephalometric radiographs were carried out and were used to obtain angular and linear measurements of anatomic structures displayed. All markings and measurements were performed by a single examiner. RESULTS: The average ANB was increased in groups with SCA (5.47 ± 2.0°) and SCT (3.80 ± 1.4°), indicating a tendency to Class II. The mean SNA angle was 83.0 ± 3.8° and 82.1±3.5° for SCA and SCT, indicating a proper positioning of the jaw from the skull base. There was an interaction between the group and sex factors for the variable SN-GoGn; measures were higher for men in the SCA group. CONCLUSION: Patients with SCA and SCT exhibited characteristics of Class II skeletal pattern because of mandibular retrusion. Most patients showed no compensatory maxillary expansion, which was determined by the normal jaw length and absence of maxillary protrusion.

Ultrasonido doppler transcraneal en la prevención del accidente vascular encefálico en niños con drepanocitosis / Transcranial doppler ultrasound in the prevention of cerebrovascular accident in children with sickle cell disease

Introducción: las complicaciones neurológicas y sus secuelas se conocen casi desde la primera descripción de la depranocitosis y son más frecuentes en la anemia drepanocítica. Varían con la edad; pueden ser agudas o crónicas y producen una elevada morbimortalidad. Objetivo: conocer la frecuencia de niños con AD que tienen alteraciones en la velocidad del flujo sanguíneo cerebral, relacionar estas alteraciones con los eventos clínicos y los datos de laboratorio y evaluar la evolución en el tiempo de los pacientes con alteraciones y su asociación con el uso de hidroxiurea. Métodos: se realizó un estudio prospectivo analítico que incluyó a 50 pacientes con anemia drepanocítica con edades comprendidas entre 5 y 18 años, atendidos en el Instituto de Hematología e Inmunología. Se determinaron las alteraciones del flujo sanguíneo cerebral (FSC) y su asociación con otros elementos clínicos y hematológicos. Resultados: las arterias que mayor velocidad del FSC mostraron fueron la arteria cerebral media derecha (121,6 cm/s) y la izquierda (115 cm/s). Las alteraciones de la velocidad del FSC en el ultrasonido doppler transcraneal (UDTC) fueron: 11 (22 por ciento) pacientes con velocidades mayores de 170 cm/s, 6 (12 por ciento) con un flujo entre 170 ­ 199 cm/s, y 5 (10 por ciento) mayor de 200 cm/s. Existió una correlación inversa entre la velocidad del FSC con la edad y las cifras de hemoglobina, y directa con la cifra de plaquetas. El accidente vascular encefálico, las transfusiones y las hospitalizaciones fueron los eventos clínicos más frecuentes en los pacientes con UDTC anormal. Las velocidades del FSC disminuyeron significativamente (31 cm/s; p = 0,034) en los pacientes que recibieron tratamiento con hidroxiurea. Conclusiones: la detección de alteraciones en el UDTC permite detectar el riesgo de AVE y adoptar las medidas oportunas de prevención del AVE(AU)

Introduction: neurological complications and their sequelae are known almost since the first description of sickle cell disease, most commonly in sickle cell anemia. They vary with age, can be acute or chronic and produce high morbidity and mortality. Aims: to determine the frequency of children with AD who have alterations in cerebral blood flow velocity, relate these changes to clinical events and laboratory data and assess the evolution over time of patients with abnormalities and their association with the use of hydroxyurea. Methods: a prospective analytical study involving 50 patients with sickle cell disease, aged 5 to 18, was performed in at the Institute of Hematology and Immunology where they are assisted. Alterations in cerebral blood flow (CBF) and the association with other clinical and hematological elements were determined. Results: the arteries that showed larger speed were right middle cerebral artery (121.6 cm/s) and left (115 cm/s). Patients with impaired CBF velocity in transcranial Doppler ultrasound were 11 ( 22 percent) with speeds greater higher than 170 cm/s , 6 patients (12 percent) with a flow between 170-199 cm/s, and five (10 percent) greater higher than 200 cm / s. There was an inverse correlation between CBF velocity with age and hemoglobin levels and directly with the platelet count. The cerebrovascular accident, blood transfusions and hospitalizations were the most frequent clinical events in patients with abnormal transcranial doppler ultrasound. FSC velocities were significantly decreased (31 cm /s; p = 0,034) in patients receiving treatment with hydroxyurea. Conclusions: Patients with alterations in the transcranial Doppler ultrasound must be included in a program for primary prevention of cerebrovascular accident(AU)

Discovery of a renal medullary carcinoma in an adolescent male with sickle cell trait by Tc-99m methylene disphosponate bone scintigraphy.

The renal excretion of Tc-99m bone imaging agents often permits the identification of urinary tract abnormalities on bone scans. In this case report, identification of focal intrarenal stasis of the excreted bone imaging agent led to additional anatomic imaging and the identification of a renal medullary carcinoma (RMC) in an adolescent black male undergoing evaluation for back pain. RMC is a rare, highly aggressive renal neoplasm found almost exclusively in young individuals with sickle cell trait (SCT) or hemoglobin SC disease. The prognosis of RMC is poor because the malignancy is usually refractory to chemotherapy and radiotherapy, with metastatic disease commonly present at the time of diagnosis.

Focal renal infarction: an unusual cause of haematuria in a patient with sickle cell trait.

A 29-year-old woman with sickle cell trait developed persistent haematuria. Intravenous urography, ultrasound, cystoscopy and selective renal angiography revealed focal renal infarction, but in the absence of papillary necrosis. There are no prior reports of focal renal infarction as a cause of haematuria in patients with sickle cell trait.

Splenic function in persons with sickle cell trait at moderately high altitude.

We investigated the possibility that persons with sickle cell trait who reside chronically at moderately high altitude might develop impaired splenic reticuloendothelial function. Seventeen healthy young black men with sickle trait who had lived at greater than or equal to 1,609 m for greater than or equal to 10 years participated in the study along with 25 matched control subjects with normal hemoglobin. Splenic function was assessed by radionuclide liver-spleen scanning and by red cell pit counts. No evidence of impaired splenic function was found in the sickle trait group. The data suggest that long-term residence at moderately high altitude does not place persons with sickle cell trait at risk for splenic dysfunction.

Focal nodular hyperplasia of the liver: a link with sickle cell disease?

Focal nodular hyperplasia is a benign liver tumour that is rare in children. We report the second case of a child with sickle cell disease presenting with symptomatic focal nodular hyperplasia. The possible pathogenesis of focal nodular hyperplasia and the association with sickle cell disease are discussed.

The defect in pulmonary gas transfer in patients with sickle cell disease.

Nine patients with sickle cell disease and without concomitant cardiopulmonary illness or acute problems were studied with lung function tests. Besides arterial hemoglobin unsaturation, found in all cases so studied, a slight decrease in PaO2 was also present. The pulmonary gas transfer defect was studied and found to be due mostly to increased right to left shunting, although uneven ventilation/perfusion relationships seem to have been a factor in a few cases. Our data clearly show that the diffusion was not implicated in the gas transfer defect. The clinical implications of this little studied and less mentioned respiratory defect are discussed. Since the defect may enhance the risk of sickling crises, it should be measured in each individual patient, for appropriate prophylactic measures. After accidents, pre and post-operatively and during acute respiratory illness, the defect should be again reevaluated. In all probability many patients will be discovered who represent a respiratory risk, and may require special immunizations, prophylactic antibiotics, professional relocation and, during emergencies, intensive respiratory care.