Quantitative Analysis of Howell-Jolly Bodies in Children with Sickle Cell Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3586-3586
Author(s):  
Russell E. Ware ◽  
Stephen Dertinger ◽  
Thad A. Howard ◽  
Sherri A. Zimmerman
Keyword(s):  
Flow Cytometry ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Genotoxic Damage ◽  
Splenic Function ◽  
Flow Cytometric ◽  
Increased Risk ◽  
Blood Specimens ◽  
Serial Measurements

Abstract Children with sickle cell disease (SCD) have repeated vaso-occlusion within the spleen, which leads to early loss of splenic filtration function and an increased risk of sepsis from encapsulated bacteria. Functional asplenia in SCD is believed to be a gradual and cumulative process that occurs during the first few years of life, although quantitative analyses of splenic function have not been readily available. Litron has recently developed a novel high-throughput flow cytometric method of quantitating Howell-Jolly bodies (HJB, also known as micronuclei), standardized using venous blood collected in heparin and fixed within 2 hours of collection. This novel technique may be useful for understanding the normal physiological decline in splenic function that occurs in SCD. Since erythrocytes that contain HJB are normally cleared by the healthy spleen, the frequency of HJB inversely reflects splenic filtration function. To investigate the utility of this novel assay for children with SCD, a tiny aliquot (10 μL) of leftover discarded blood specimens was obtained from unselected children receiving routine clinical care in the Duke Pediatric Sickle Cell Program, fixed in ultracold methanol, stored at −80C, and then shipped to Litron for flow cytometric analysis. Erythrocytes containing HJB were identified by flow cytometry: mature CD71− erythrocytes that contain HJB are an accepted surrogate marker of splenic filtration, while HJB within the youngest CD71+ erythrocytes may reflect genotoxic damage associated with increased chromosome breaks. Initial studies determined that blood collected in EDTA was acceptable for analysis; no differences were noted with EDTA collection compared to heparin (R2=.994, n=5, p<.001). Samples fixed after 24 hours of refrigeration also showed excellent correlation with samples fixed within 2 hours (R2=.996, n-16, p<.001); blood stored for 48 hours also gave reliable results. Samples analyzed in duplicate or triplicate demonstrated high intrasample reproducibility (R2=.998, n=8, p<.001). To investigate the clinical utility of this assay, de-identified blood specimens were analyzed using EDTA-anticoagulated blood samples fixed 24-hours after collection. Children with HbSS (n=126) had increased numbers of HJB within mature CD71− erythrocytes (2504±2311 per million RBC versus 28±42 in 50 healthy controls, p<.001). The frequency of HJB was more prevalent with increased age (R2=0.30, p<.001). For HbSS children without splenectomy or hydroxyurea (HU) exposure, 89% over age 1 year, and 100% over age 3 years had >300 HJB per million RBC. Children with HbSC (n=20) had a lower frequency of HJB (131±228 per million RBC), and only 10% with >300 HJB per million RBC. Increased HJB in HbSS patients were also identified in the young CD71+ erythrocytes (0.43±0.40%, n=126, normal <0.08%). Children with HbSS and HU exposure had significantly higher numbers of HJB in CD71+ erythrocytes (0.67±0.50%, n=46) compared to children without HU exposure (0.22±0.13%, n=59, p<.001). Serial measurements in one young child on HU therapy showed decreased HJB frequency, suggesting recovery of splenic function. Quantitation of HJB by flow cytometry is a rapid, robust, and reproducible assay that will be valuable in studies of organ damage in children with SCD. Serial measurements are needed to assess preservation or recovery of splenic filtration function, as well as genotoxic damage associated with HU therapy.

scholarly journals Increased Expression of Type 1 Interferon Stimulated Genes in Sickle Cell Disease and a Potential Association with RBC Alloimmunization

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 716-716
Author(s):  
Emaan Madany ◽  
Najwa El Kadi ◽  
Sumaarg Pandya ◽  
Jeanne E. Hendrickson ◽  
David R Gibb
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Flow Cytometric Analysis ◽  
Gene Signature ◽  
Cell Disease ◽  
Interferon Stimulated Genes ◽  
Flow Cytometric ◽  
Increased Risk ◽  
Significant Difference

Background RBC transfusion can lead to the production of alloantibodies against RBC antigens and is a clinically significant issue in transfusion medicine. Patients with sickle cell disease have an increased risk for alloimmunization; 30-50% of SS patients have alloantibodies compared to 3-10% of other hospitalized patients. These alloantibodies can cause dangerous hemolytic transfusion reactions and limit the availability of compatible antigen-negative RBC products. This is of particular importance in SS patients, who commonly make alloantibodies against multiple RBC antigens and need regular transfusions to treat their disease. However, mechanisms underlying the increased frequency of alloimmunization in sickle cell patients are poorly understood. In previous studies, inflammation in the recipient has been shown to promote alloimmunization in both mice and humans. In mouse transfusion models, type 1 interferons (IFNα/β) and Interferon Stimulated Genes (ISGs) have been shown to promote alloimmunization. Other studies have shown that patients with inflammatory autoimmune diseases express an IFNα/β signature, which may contribute to the increased frequency of alloimmunization in these populations. Given the chronic inflammatory state in patients with sickle cell disease, we hypothesize that: SS patients may also have an IFN gene signature that may contribute to the increased frequency of alloimmunization. Methods To test this hypothesis, we initially measured the expression of the ISG, myxovirus resistance protein 1 (MxA), in the blood of previously-transfused patients (n=50) with SS disease (SS, n=13) and without SS disease (ββ, n=37) by whole blood immunoassay (ELISA). We then measured expression of another ISG, Siglec-1 (SS n=5, ββ=24), expressed on monocytes by flow cytometric analysis. To determine the degree to which ISG expression correlated with alloimmunization frequency, expression of MxA in non-alloimmunized patients was compared to the expression in patients with 1 or more alloantibodies. Statistical analysis of 2 groups was completed with a Mann-Whitney U test. Significance between 3 groups was determined using a Kruskal-Wallis test with a Dunn's post-test. Results SS patients had significantly elevated levels of MxA (mean ± standard error of the mean, SS MxA = 8.98 ng/mL ± 2.46) compared to control patients without SS (MxA = 1.25 ± 0.54, p&lt;0.0001). (Figure 1 A). SS patients also had significantly elevated levels of Siglec-1 on blood monocytes, measured by flow cytometric mean fluorescence intensity (MFI, SS MFI = 132.72 ± 42.9, ββ MFI = 64.9 ± 6.17, p&lt; 0.05). (Figure 1 B,C). For all 50 patients, including SS and ββ control patients, there was a trend toward elevated MxA expression in alloimmunized patients. Patients with 2 or more alloantibodies had significantly elevated MxA (MxA 8.16 ± 2.61), compared to non-alloimmunized transfused patients (MxA = 2.05 ± 1.65, p &lt; 0.01) or patients with only 1 alloantibody (MxA = 1.18 ±0.48, p&lt;0.01). There was no significant difference in MxA levels between patients with 0 and 1 alloantibody. Of the 13 patients with SS disease, only 2 patients lacked alloantibodies. (SS with 1 alloantibody, n=3, SS with 2 or more alloantibodies, n=8). Therefore, a correlation between MxA levels and alloimmunization in SS patients could not be assessed. Discussion Factors that contribute to RBC alloimmunization in sickle cell disease are poorly understood. In this study, we found that sickle cell patients had an increase in the expression of ISGs compared to other transfused patients. We also found that MxA levels are increased in patients that have 2 or more alloantibodies compared to patients without alloantibodies. These findings suggest the presence of an IFNα/β gene signature in patients with sickle cell disease. Further studies are needed to determine the relationship between interferon-stimulated responses in sickle cell patients and the increased frequency of alloantibody production. Disclosures No relevant conflicts of interest to declare.

Splenic function in Saudi children with sickle cell disease

1984 ◽  
Vol 4 (2) ◽  
pp. 87-91 ◽  
Author(s):  
Ahmad Mallouh ◽  
G. M. Burke ◽  
M. Salamah ◽  
M. S. Ahmad
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Splenic Function

Lead Neuropathy and Sickle Cell Disease

PEDIATRICS ◽  
1974 ◽  
Vol 54 (4) ◽  
pp. 438-441
Author(s):  
Gerald Erenberg ◽  
Steven S. Rinsler ◽  
Bernard G. Fish
Keyword(s):  
Case Report ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Lead Poisoning ◽  
Cell Disease ◽  
Hemoglobin S ◽  
Increased Risk ◽  
Rare Manifestation ◽  
Poisoning In Children

Four cases of lead neuropathy in children with hemoglobin S-S or S-C disease are reported. Neuropathy is a rare manifestation of lead poisoning in children, and only ten other cases have been well documented in the pediatric literature. The last previous case report of lead neuropathy was also in a child with hemoglobin S-S disease. The neuropathy seen in the children with sickle cell disease was clinically similar to that seen in the previously reported cases in nonsicklers, but differed in both groups from that usually seen in adult cases. It is, therefore, postulated that children with sickle cell disease have an increased risk of developing neuropathy with exposure to lead. The exact mechanism for this association remains unknown, but in children with sickle cell disease presenting with symptoms or signs of peripheral weakness, the possibility of lead poisoning must be considered.

scholarly journals A case of severe multi-system disease in a sickle cell SC patient caused by parvovirus B19 infection

2021 ◽  
Vol 2 (5) ◽  
Author(s):  
Mohamed Almuqamam ◽  
◽  
Swetha Madhavarapu ◽  
Nataly Apollonsky ◽  
◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Parvovirus B19 ◽  
Acute Infection ◽  
Organ Injury ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Splenic Sequestration ◽  
Increased Risk ◽  
Parvovirus B19 Infection

Sickle Cell Disease (SCD) is an inherited hemoglobinopathy, which results in production of abnormal hemoglobin S. HbSC disease is a variant of SCD, which shares a similar clinical complication profile to HbSS disease, but often thought to be a milder condition. In patients with SCD, Hb S in deoxygenated state undergoes polymerization, leading to hemolysis, vaso-occlusive events, and eventually end-organ damage. Among other complications in patients with SCD is increased risk of complications caused by parvovirus B19. We present a case of a 14-year-old female with HbSC disease who presented to the emergency room with complaint of abdominal pain and found to have splenic sequestration. Splenic sequestration progressed rapidly, Hemoglobin (hb) dropped to 4.6 g/dl and acute chest syndrome (ACS) developed. She was treated following the ACS protocol, received 4 units of Packed Red Blood Cells (PRBC) and subsequently underwent a single volume PRBC exchange transfusion. Considering her unusual presentation, with severe ARDS from alveolar hemorrhage requiring mechanical ventilation and multi-organ injury, several autoimmune and infectious conditions with a cytokine storm component including COVID-19 disease, were considered. Results of viral testing revealed parvovirus B19 IgM antibodies signifying an acute infection. She fully recovered with supportive care and was discharged home. Multisystem involvement simulating connective tissue disorders or malignancies with acute parvovirus B19 infection has been reported and is considered extremely rare. To our knowledge, there were no reports of pediatric patients with SC disease presenting with splenic sequestration and ACS in the setting of parvovirus B19 multisystem disease. Keywords: sickle cell disease; acute respiratory distress syndrome; acute chest syndrome; parvovirus B19.

scholarly journals Review of Sickle Cell Disease and Spinal Pathology

2018 ◽  
Vol 9 (7) ◽  
pp. 761-766 ◽  
Author(s):  
Hayeem L. Rudy ◽  
David Yang ◽  
Andrew D. Nam ◽  
Woojin Cho
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Vertebral Osteomyelitis ◽  
Compression Fracture ◽  
Symptomatic Therapy ◽  
Cell Disease ◽  
Blood Disorder ◽  
Increased Risk ◽  
Adequate Hydration ◽  
Surgical Treatments

Study Design:Sickle cell disease (SCD) is a relatively common blood disorder that has profound implications on the musculoskeletal system and particularly the spine; however, there is a paucity of data in the literature discussing this important topic.Objectives:(1) To elucidate common spinal pathologies affecting patients with SCD, as well as the medical and surgical treatments available for these patients. (2) To discuss indications for surgical management of spinal complications of SCD and important for orthopedic surgeons when taking patients with SCD to the operating room.Methods:A narrative review of the literature was performed.Results:Patients with SCD have a significantly higher risk of developing spinal pathologies including vertebral osteomyelitis, compression fracture, vertebral vaso-occlusive crises, and osteoporosis, among others. In addition, patients with sickle cell disease are particularly susceptible to developing perioperative and post-operative complications including surgical site infection, implant malfunction, and vertebral body compression fracture. Postoperatively patients with SCD are prone to developing complications and adequate hydration is necessary in order to reduce complications of SCD.Conclusions:Several spinal pathologies may arise secondary to SCD and distinguishing these pathologies from one another may be challenging due to similarities in symptoms and inflammatory markers. Although most patients with SCD can benefit from conservative treatment involving rest, symptomatic therapy, antibiotic therapy, and/or orthosis, surgical intervention may be indicated in certain cases. It is preferable to avoid surgery in patients with SCD due to an increased risk of complications such as wound infection and vaso-occlusive crisis.

Sickle cell trait and the risk of venous thromboembolism among blacks

Blood ◽  
2007 ◽  
Vol 110 (3) ◽  
pp. 908-912 ◽  
Author(s):  
Harland Austin ◽  
Nigel S. Key ◽  
Jane M. Benson ◽  
Cathy Lally ◽  
Nicole F. Dowling ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Odds Ratio ◽  
Sickle Cell Trait ◽  
Coagulation System ◽  
Cell Disease ◽  
Hemoglobin C ◽  
Increased Risk ◽  
S Allele

Abstract People with sickle cell disease have a chronically activated coagulation system and display hemostatic perturbations, but it is unknown whether they experience an increased risk of venous thromboembolism. We conducted a case–control study of venous thromboembolism that included 515 hospitalized black patients and 555 black controls obtained from medical clinics. All subjects were assayed for hemoglobin S and hemoglobin C genotypes. The prevalence of the S allele was 0.070 and 0.032 for case patients and controls, respectively (P < .001). The odds that a patient had sickle cell trait were approximately twice that of a control, indicating that the risk of venous thromboembolism is increased approximately 2-fold among blacks with sickle cell trait compared with those with the wild-type genotype (odds ratio = 1.8 with 95% confidence interval, 1.2-2.9). The odds ratio for pulmonary embolism and sickle cell trait was higher, 3.9 (2.2-6.9). The prevalence of sickle cell disease was also increased among case patients compared with controls. We conclude that sickle cell trait is a risk factor for venous thromboembolism and that the proportion of venous thromboembolism among blacks attributable to the mutation is approximately 7%.

Haemoglobinopathies

2013 ◽  
Author(s):  
David Rees
Keyword(s):  
Bone Marrow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Lupus Erythematosus ◽  
Single Gene ◽  
Globin Genes ◽  
Globin Chain ◽  
Cell Disease ◽  
Increased Risk ◽  
Marrow Expansion

Inherited abnormalities of the globin genes are the commonest single-gene disorders in the world and fall into two main groups: thalassaemias and sickle cell disease. Thalassaemias are due to quantitative defects in globin chain synthesis which cause variable anaemia and ineffective erythropoiesis. Thalassaemia was initially thought to be a disease of the bones due to uncontrolled bone marrow expansion causing bony distortion, although this is now unusual with appropriate blood transfusions. Osteopenia, often severe, is a feature of most patients with thalassaemia major and intermedia, caused by bone marrow expansion, iron overload, endocrinopathy, and iron chelation. Treatment with bisphosphonates is generally recommended. Other rheumatological manifestations include arthropathy associated with the use of the iron chelator deferiprone. Sickle cell disease involves a group of conditions caused by polymerization of the abnormal -globin chain, resulting in abnormal erythrocytes which cause vaso-occlusion, vasculopathy, and ischaemic tissue damage. The characteristic symptom is acute bone pain caused by vaso-occlusion; typical episodes require treatment with opiate analgesia and resolve spontaneously by 5 days with no lasting bone damage. The frequency of acute episodes varies widely between patients. The incidence of osteomyelitis is increased, particularly with salmonella, although it is much rarer than acute vaso-occlusion. Avascular necrosis can affect the hips, and less commonly the shoulders and knees. Coincidental rheumatological disease sometimes complicates the condition, particularly systemic lupus erythematosus (SLE) which is more prevalent in populations at increased risk of sickle cell disease.

scholarly journals Identification of Clinical and Laboratory Parameters Associated with the Development of Acute Chest Syndrome during Vaso-Occlusive Episodes in Children with Sickle Cell Disease: A Preliminary Step before Assessing Specific and Early Treatment Strategies

2019 ◽  
Vol 8 (11) ◽  
pp. 1839
Author(s):  
Madhi ◽  
Kamdem ◽  
Jung ◽  
Carlier-Gonod ◽  
Biscardi ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Pain Score ◽  
Sickle Cell ◽  
Multivariate Model ◽  
Red Blood Cell Transfusion ◽  
Predictive Score ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Laboratory Parameters ◽  
Increased Risk

This prospective observational study sought to ascertain clinical and laboratory parameters associated with the development of acute chest syndrome (ACS) during vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD). It was performed at the pediatric department of the university Intercommunal Créteil hospital. All children with SCD (all sickle genotypes) consecutively admitted from November 2013 to December 2016 for painful VOEs and no evidence of ACS were included. Clinical and laboratory parameters collected at admission and within 48 h after admission were compared for children in whom ACS developed or not. Variables that were statistically significant on univariate analysis or considered to be clinically relevant were included in a multivariable model to ascertain the risk factors associated with the development of ACS during a VOE. The variables retained in the multivariate model were used to construct a predictive score for ACS. For each included child and during the study period, only data from the first VOE and/or the first ACS were analyzed. Among 191 hospitalizations for painful VOEs, for 176 children with SCD, ACS developed in 35 during hospitalization. Mean hospital stay was longer for children with ACS versus VOEs alone (7.6 (±2.3) vs. 3.3 (±1.8) days, p < 0.0001), and all children with ACS versus 28/156 (17.9%) with VOEs alone received red blood cell transfusion (p < 0.0001). The multivariate model retained pain score (≥9/10), pain localization (abdominal or spinal pain or involving more than two limbs), and high reticulocyte (≥260 × 109/L) and neutrophil (>10 × 109/L) counts, at admission, as independently associated with ACS development. The area under the receiver operating characteristic curve for the ACS predictive score was 0.82 (95% CI: 0.74–0.89), and the negative predictive value was 97.7%. The evolution profiles during the first 48 h differed between children with ACS and VOEs alone, with a more rapid decline of pain score and leucocytosis in children with VOEs. Clinical and laboratory measurements at admission may be simple parameters to identify children with increased risk of ACS development during VOEs and to facilitate early diagnosis of this respiratory complication. Also, the persistent elevation of leukocyte count on day 2 may be considered a sign of evolving ACS.

scholarly journals Perioperative Endocarditis Management in a Patient with Homozygous Sickle Cell Disease

2019 ◽  
Vol 08 (01) ◽  
pp. e1-e4 ◽  
Author(s):  
Malgorzata Gozdzik ◽  
Sergio Mariotti ◽  
Michele Genoni ◽  
Alicja Zientara
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Heart Surgery ◽  
Open Heart Surgery ◽  
Cell Disease ◽  
Coagulase Negative Staphylococci ◽  
Right Heart ◽  
Double Valve Replacement ◽  
Increased Risk ◽  
Homozygous Sickle Cell Disease

Background Homozygous sickle cell disease (SCD) compounded with bacterial endocarditis makes open-heart surgery a multidisciplinary challenge. Case description A 45-year-old African male patient with homozygous SCD presented with right heart decompensation, tricuspid regurgitation, and endocarditis of the aortic valve. Blood coulters were positive for coagulase-negative staphylococci. An emergent double valve replacement was successfully performed involving a multidisciplinary team. Conclusion Homozygous SCD is associated with an increased risk of preoperative vaso-occlusive complications. Surgery with cardiopulmonary bypass can be performed, if hypothermia, hypoxia, acidosis, or low-flows are being avoided. Due to the lack of data, the adequate approach is still intuitive and requires standardization.

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