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

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<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< 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 < 0.01) or patients with only 1 alloantibody (MxA = 1.18 ±0.48, p<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.

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Purification Platelets from Mouse Blood with Sickle Cell Disease Using Iohexol Gradient Medium

Blood ◽

10.1182/blood-2019-128459 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4888-4888

Author(s):

Md Nasimuzzaman

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Blood Cells ◽

Flow Cytometric Analysis ◽

Cell Disease ◽

Mouse Blood ◽

Simple Method ◽

Flow Cytometric ◽

Microscopic Evaluation ◽

Gradient Medium

Platelets are purified from whole blood to study their functional properties, which should be free from red blood cells (RBC), white blood cells (WBC), and plasma proteins. Since RBC and WBC contain significantly more RNA and proteins than platelets, the presence of even a small number of these cells can interfere with transcriptomic and proteomic analyses of RNA and proteins derived from platelets. Several protocols have described the isolation of platelets from human, dog, rat, and non-human primate by various methods. Some of the methods require multiple steps such as collection of platelet-rich plasma by centrifugation, filtration by separation column, negative selection of platelets with RBC- and WBC-specific antibody conjugated to magnetic beads, and so on, which are time-consuming and may degrade platelets and their contents. Moreover, mouse blood with sickle cell disease contains a significant level of fragments of RBC which should be removed from the platelet preparation. However, the mouse yields a relatively smaller volume of blood, which makes it difficult to purify platelets. If the same small volume of gradient medium and blood samples are used, the platelet layer cannot be clearly separated from RBC-WBC layer after centrifugation. We describe a simple method for purification of platelets from mouse blood with sickle cell disease using three-fold more iohexol gradient medium relative to blood sample volume and centrifugation in a swinging bucket rotor at 400 x g for 20 min at 20 °C. The platelet layer is collected and centrifuged again at 200 x g for 20 min at 20 °C to remove the residual fragments of RBC. The recovery/yield of the purified platelets were 10-17%, and the purified platelets were in a resting state, which did not contain any significant number of RBC and WBC. The purified platelets were activated with thrombin indicating their viability. We confirmed that the purified platelets were sufficiently pure using flow cytometric and microscopic evaluation. Although flow cytometric analysis of purified platelet from sickle cell disease mice showed a few RBC events after staining with anti-TER119 antibody, the microscopic study did not show any intact RBC or larger fragments indicating that these are smaller fragments of RBC which do not interfere with the biochemical and functional studies. This method can be used for purification of platelets from the blood of other species and disease models as well. Disclosures No relevant conflicts of interest to declare.

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Type I Interferon Gene Signature in Peripheral Blood Mononuclear Cells of Sickle Cell Disease Patients and a Connection to RBC Alloimmunization

Blood ◽

10.1182/blood-2020-142935 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 26-27

Author(s):

Emaan Madany ◽

June Young Lee ◽

Jeanne E. Hendrickson ◽

David R Gibb

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Whole Blood ◽

Gene Signature ◽

Small Sample ◽

Type I ◽

Healthy Controls ◽

Cell Disease ◽

Interferon Gene

Background RBC alloimmunization is a clinically significant issue in transfusion medicine; patients with sickle cell disease have an increased risk of alloantibody production (30-50% of SS patients) compared to that of other hospitalized patients (3-10%). 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. Transfusion models, type 1 interferons (IFNα/β) and Interferon Stimulated Genes (ISGs) have been shown to promote alloimmunization in mice. 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. One recent study reported significantly elevated ISGs in neutrophils as well as evidence that IFNα is upregulated in SS patients compared to controls. Given the chronic inflammatory state in SS patients, we sought to determine the role of PBMCs and whether they also expressed an IFN gene signature that contributes to the increased frequency of alloimmunization. Methods The expression of the ISG, myxovirus resistance protein 1 (MxA), was measured in the blood of SS patients with more patients with SS disease (SS, n=13) and race matched healthy controls (ββ, n=3) by whole blood immunoassay (ELISA). qPCR was performed on 5 previously established ISGs to determine an IFN score, a measure of overall gene expression, from whole blood and IFNβ stimulated PBMCs of SS patients (SS, n=15) and healthy race matched controls (ββ, n=5). A LEGENDplex™ Human Anti-Virus Response Panel assay was used to determine the expression of various type 1 IFNs, cytokines and ISGs in patients with SS disease (SS, n=15) and healthy race matched controls (ββ, n=5). Results SS patients had significantly elevated levels of MxA (mean ± standard error of the mean, SS MxA = 12.27 ng/mL ± 15.68) compared to control patients without SS (ββ MxA = 1.52 ng/mL± 0.26, p< 0.05) (Figure 1 A) . The Legendplex showed a significant increase in IL-6, IL-10 and the ISG, IP-10. (SS IP-10= 147.81 pg/mL ± 49.24) (ββ IP-10 = 68.85 pg/mL ±10.70, p<0.01) (Figure 1 B) Analyzing the 5 ISGs, we saw a trend towards a higher IFN score in patients with SS disease than healthy controls in whole blood; this difference was significant in PBMCs stimulated with IFNB (IFN Score SS = 20.76 ± 17.18 ,ββ = 0.00 ± 3.71 , p<0.01) (Figure 1 C). Discussion SCD is a complex disease with many environmental and genetic factors that play roles in the severity of the disease. Any number of these factors may influence the high rates of alloimmunization found in sickle cell patients. We found increased cytokines, ISGs and IFN scores in SS patients compared to healthy controls. These findings suggest the presence of an IFNα/β gene signature in patients with sickle cell disease. Due to the relatively small sample size, we are unable to determine a correlation between alloantibodies and MxA levels or high IFN scores with this cohort. Further studies will allow us to determine if the increased interferon gene signature plays a role in the increased alloimmunization burden that these patients experience. Disclosures No relevant conflicts of interest to declare.

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Report on the International Co-Operative Study of the Effects of L-Selectin Gene Polymorphisms on the Development of Complications in Sickle Cell Disease.

Blood ◽

10.1182/blood.v106.11.3775.3775 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3775-3775

Author(s):

Iheanyi Okpala ◽

Cynthia C. Ugochukwu ◽

Panagiotis Pantelidis ◽

Baba Inusa ◽

Obike Ibegbulam ◽

...

Keyword(s):

Steady State ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Surface Expression ◽

Control Individual ◽

Acute Chest Syndrome ◽

Nucleotide Polymorphisms ◽

Cell Disease ◽

Increased Risk ◽

Significant Difference

Abstract Our previous study showed that patients with sickle cell disease (SCD) and high steady-state expression of the adhesion molecules L-selectin and αMβ2 integrin on leukocytes developed complications [Blood. 2002;100(suppl):11a. Eur J. Haematol. 2002; 69:135–144]. The aim of this study was to find out if L-selectin protein expression by leukocytes and the development of complications in SCD are affected by previously described single nucleotide polymorphisms within the coding regions of the gene. To detect F206L, T49S and P213S polymorphisms we determined the L-selectin genotype in 142 HbSS patients (64M, 78F, age 2 – 62 yr, mean 27 yr ±12); and 102 racially-matched HbAA controls with similar age and sex distribution. The T49S and P213S amino acid changes in L-selectin are respectively associated with increased risk of vasculopathy and nephropathy; important features of SCD. [Hum Genet. 1996; 97:15–20. Am. J. Hum. Genet.2002; 70: 781–786]. All HbSS patients were evaluated for disease complications. Steady-state expression of L-selectin on neutrophils, lymphocytes and monocytes was measured by flow cytometry in 44 HbSS patients. With respect to F206L polymorphism, 100/142 (70%) patients and 73/102 (72%) controls were FF homozygous, 42 patients and 28 controls were heterozygous FL, and 1 control individual was LL homozygous. There was no significant difference in distribution of the polymorphic variants between patients and controls [Chi-squared (X2) = 0.1, p>0.05]. In codon 213, 48 (33.8%) patients and 42 (41.2%) controls were PP homozygous, 91 patients and 55 controls PS heterozygous, 1 patient and 5 controls SS homozygous [X2 =1.9, p>0.05]. With regard to the T49S polymorphism, 100% of the patients and controls were TT homozygous. At least one complication of SCD was observed in 110 SCD patients; 32 had uncomplicated disease. The most common complications observed were avascular joint necrosis (n=39), sickle nephropathy (n=31), stroke (n=25) and acute chest syndrome (n=20). The observed frequencies of FF genotype in codon 206 among patients with complications (74), and without complication (26) were not significantly different from the expected values [X2 = 2.37, p>0.05]. Similarly, none of the other genotypes (FL, PP, PS) was significantly associated with complications of SCD. Of the 44 patients in who leukocyte L-selectin expression was measured, 31 turned out to be FF homozygous in codon 206, and 13 FL. No significant differences were observed between FF and FL patients in the mean levels of L-selectin expression by neutrophils (FF: 4.00+ 4.56 vs FL: 3.24+ 3.4), monocytes (FF: 4.30+ 5.6 vs FL: 2.56+ 3.39) or lymphocytes (FF: 2.61+ 3.02 vs FL: 2.11+ 2.0); p>0.05. Similarly, the P213S polymorphism had no effect on the level of L-selectin expression. The findings suggest that neither F206L nor P213S L-selectin gene polymorphism predisposes to high leukocyte surface expression of this adhesion molecule, or the development of complications in SCD.

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The Effect of Splenectomy on Development of Cerebral Vasculopathy in Children with Sickle Cell Disease

Blood ◽

10.1182/blood.v128.22.3647.3647 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3647-3647

Author(s):

Azada Ibrahimova ◽

Bruce Bernstein ◽

Rida Abid ◽

Nataly Apollonsky

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Sickle Cell Disease ◽

Protective Effect ◽

Sickle Cell ◽

Cerebral Artery ◽

Cell Disease ◽

Increased Risk ◽

Significant Difference ◽

History Of

Abstract Splenic complications are often seen in pediatric patients with sickle cell disease and could lead to an increase in morbidity and mortality. The most common splenic event is acute splenic sequestration crisis (ASSC) which has been often managed with surgical splenectomy. Although splenectomy has been the treatment of choice for years, the long term complications of splenectomy on vascular events has not been broadly assessed. It has been reported that splenectomy could lead to vascular complications and increased risk of thrombosis in chronic hemolytic conditions. As it was proposed, it could be partially due to the shift form extravascular hemolysis to intravascular leading to the scavenging of nitric oxide (Kato et al, 2007). In terms of cerebral vasculopathy in children with sickle cell disease, screening is usually done by measuring blood flow velocity in the main cerebral arteries using Transcranial Doppler Ultrasonography (TCD). In 2014 Peter Soh and Abdul Siddiqui reported an increased risk of cerebrovascular complications in splenectomized patients with sickle cell disease (3), but it has not been confirmed by other publications. The aim of our study is to evaluate how splenectomy affects cerebral blood flow measured by TCD in patients with homozygous HbS. The secondary aim is to evaluate if Hydroxyurea (HU) has a protective effect on the development of cerebral vasculopathy in splenectomized patients. We performed a retrospective chart review of patients with sickle cell disease Hb SS and Hb S beta thalassemia followed at the Marian Anderson Center at St. Christopher's Hospital for Children, Philadelphia between 1999 and 2016. In the final analysis we included TCD data on 153 patients, of which 36 had undergone splenectomy. A total of 516 TCD studies were collected, of which 145 patients had a history of splenectomy. Of the 516 TCD assessments in this sample, 70 (13.6%) patients were on HU of which 21 had undergone splenectomy. Pearson correlations were calculated to explore linear associations of mean cerebral blood flow velocities (CBFV) with age at the time of TCD assessment, time since splenectomy, and TCD values. Associations of CVFV with splenectomy and with HU administration for splenectomy patients were analyzed with analysis of covariance (ANCOVA). The association of time elapsed since splenectomy to TCD measure, adjusting for age at TCD assessment, was explored with multiple linear regression models. Statistical analysis was conducted with SPSS ver. 24.0. Age at the time of TCD was significantly correlated with mean right cerebral artery (RMCA) (r = -.199, p < .001), LMCA (r = -.181, p < .001), RDICA (r = -.110, p = .047), LDICA (r = -.142, p = .01) and Basilar (r = -.186, p = < .001) velocities. Tables 1 and 2 present estimated mean TCD values (calculated adjusting for age at the time of TCD). In analysis of all TCDs, the estimated mean (RMCA) velocity was significantly higher in patients with history of splenectomy than in patients without splenectomy, (Table 1). There was also significant difference in LDICA, RDICA and right posterior cerebral artery (RPCA) velocities, all of which were higher in splenectomized patients (Table 1). When analyzing the velocities according to time since splenectomy, there were significant associations between years since splenectomy (0-5, 5-10 and >10years) and with both RMCA and LMCA abnormalities. Analysis of TCD results in splenectomized patients on HU versus non-HU, indicates all estimated mean TCDs except for RPCA, are lower for the patients on HU (Table 1), with RMCA and LMCA statistically significant. Based on our analysis we conclude that in patients with homozygous HbS disease history of surgical splenectomy increases the risk for cerebral vasculopathy. It remains unclear if cerebral vasculopathy develops as a result of splenectomy or if there is a preexisting factor leading to the development of both complications. The other important finding of our study is a protective effect of hydroxyurea on the development of cerebral vasculopathy in splenectomized patients. Disclosures No relevant conflicts of interest to declare.

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The Relationship of Pulmonary Hypertension and Survival in Sickle Cell Disease.

Blood ◽

10.1182/blood.v104.11.1665.1665 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1665-1665 ◽

Cited By ~ 7

Author(s):

Kenneth I. Ataga ◽

Susan Jones ◽

Oludamilola Olajide ◽

Dell Strayhorn ◽

Alice Lail ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Right Atrial ◽

Reference Ranges ◽

Cell Disease ◽

Risk Of Death ◽

Increased Risk ◽

Significant Difference

Abstract Introduction: Pulmonary hypertension (PHT) is a common complication of sickle cell disease (SCD). Most SCD patients who have PHT appear to have only mild elevations in their pulmonary artery systolic pressure (PASP). Although SCD patients with PHT have been reported to have an increased mortality, the effect of mild PHT on survival in patients with SCD remains uncertain. Methods: The study subjects represent a cohort of patients followed at the Sickle Cell Clinic at UNC, Chapel Hill. Doppler echocardiography was used to estimate the PASP. The PASP was determined by applying the modified Bernoulli equation (PASP = 4V2 + right atrial pressure), if an adequate tricuspid regurgitant velocity was observed. A subject was considered to have PHT if his/her PASP exceeded the upper limits of normal in the age- and body mass index-adjusted reference ranges. Subjects with PHT were sub-classified into mild (above normal values up to 44 mm Hg), moderate (45 – 74 mm Hg) or severe pulmonary hypertension (≥ 75 mm Hg). Patients’ data were censored at the time of their death or loss to follow-up. Results: The 60 subjects enrolled in this study have been followed for a period of 9 to 47 months (mean [± SD] of 29.8 ± 10.7 months). Pulmonary hypertension was observed in 18 subjects on initial evaluation, while the remaining 34 subjects had no evidence of PHT. The 18 subjects with PHT have been followed for 24.9 ± 10.6 months, while the 34 subjects without PHT have been followed for 31.8 ± 10.1 months. Six patients have died to date. All of these 6 patients had evidence of PHT, with estimated PASP values of 44, 44, 48, 54, 74 and 84 mm Hg (mean = 58 mm Hg) respectively. The presence of PHT was strongly associated with an increased risk of death (p = 0.0001). No other variables were associated with the risk of death in these patients. Although more patients with moderate and severe PHT died when compared to patients with mild PHT, the difference was not statistically significant. Conclusion: Pulmonary hypertension is strongly associated with an increased risk of death in patients with SCD. While our study did not find a significant difference in the risk of death when patients with mild PHT were compared to patients with more severe disease, the number of patients followed was relatively small and the duration of follow-up was short. More patients and a longer period of follow-up would be required to ascertain whether the effect of mild pulmonary hypertension on mortality is different from that of more severe PHT in patients with SCD. Figure Figure

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

Blood ◽

10.1182/blood.v104.11.3586.3586 ◽

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.

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Lead Neuropathy and Sickle Cell Disease

PEDIATRICS ◽

10.1542/peds.54.4.438 ◽

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.

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

Journal of Clinical Images and Medical Case Reports ◽

10.52768/2766-7820/1314 ◽

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.

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Pregnancies and Neonatal Outcomes in Patients with Sickle Cell Disease (SCD): Still a (High-)Risk Constellation?

Journal of Personalized Medicine ◽

10.3390/jpm11090870 ◽

2021 ◽

Vol 11 (9) ◽

pp. 870

Author(s):

Pia Proske ◽

Laura Distelmaier ◽

Carmen Aramayo-Singelmann ◽

Nikolaos Koliastas ◽

Antonella Iannaccone ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Neonatal Outcomes ◽

University Hospital ◽

High Rate ◽

Successful Outcome ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Significant Difference ◽

Tract Infections

Background: This monocentric study conducted at the University Hospital of Essen aims to describe maternal and fetal/neonatal outcomes in sickle cell disease (SCD) documented between 1996 to 2021 (N = 53), reflecting the largest monocentric analysis carried out in Germany. Methods/Results: 46 pregnancies in 22 patients were followed. None of the patients died. In total, 35% (11/31) of pregnancies were preterm. 15 pregnancies in eight patients were conceived on hydroxycarbamide (HC), of which nine had a successful outcome and three were terminated prematurely. There was no difference regarding the rate of spontaneous abortions in patients receiving HC compared to HC-naive patients prior to conception. In patients other than HbS/C disease, pregnancies were complicated by vaso-occlusive crises (VOCs)/acute pain crises (APCs) (96%, 23/24); acute chest syndrome (ACS) (13%, 3/24), transfusion demand (79%, 19/24), urinary tract infections (UTIs) (42%, 10/24) and thromboembolic events (8%, 2/24). In HbS/C patients complications included: VOCs/APCs (43%, 3/7; ACS: 14%, 1/7), transfusion demand (14%, 1/7), and UTIs (14%, 1/7). Independent of preterm deliveries, a significant difference with respect to neonatal growth in favor of neonates from HbS/C mothers was observed. Conclusion: Our data support the results of previous studies, highlighting the high rate of maternal and fetal/neonatal complications in pregnant SCD patients.

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Review of Sickle Cell Disease and Spinal Pathology

Global Spine Journal ◽

10.1177/2192568218799074 ◽

2018 ◽

Vol 9 (7) ◽

pp. 761-766 ◽

Cited By ~ 1

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.

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