Sickle Disorders Research Articles

A-149 Comparison of Mass Spectrometry to Sickle Solubility for Confirmation of Low Percentages of Hemoglobin S

Abstract Background Hemoglobin S (HbS) causes sickling disorders. In the laboratory, confirmation of HbS in patient samples with varying percentages is essential. Assessment is routinely performed using capillary electrophoresis (CE) and/or high-performance liquid chromatography. Sickle solubility (SS) exploits decreased solubility of HbS under reducing conditions and is a confirmatory test. SS is unreliable with low HbS, elevated HbF, severe anemia, erythrocytosis, hyperglobulinemia, extreme leukocytosis, hyperlipidemia, or increased serum proteins. Infant samples commonly have low percentages of HbS, high HbF, and limited sample volume. Intact globin chain Mass Spectrometry (MS) is used to identify abnormal hemoglobin variants by detecting the mass change (normal α/β/γ mass =15127/15867/15996 amu), respectively). MS has potential advantages in sensitivity and efficiency over SS and requires lower input sample volume. Herein we compare the utility of MS versus SS for confirmation of HbS. Methods Twenty-three EDTA-anticoagulated blood samples containing low percentages of HbS were identified. SS was performed on 30μL washed packed cells (requires 200μL whole blood) per standard methods. Intact Quadrupole Time-of-Flight MS (Accurate-Mass Q-TOF LC/MS 6520, Agilent Technologies, California) was performed using 10μL whole blood sample in acetonitrile solution reagent and results were compared. HbS and HbF levels were assayed by capillary electrophoresis (Sebia, France) per standard methods. Results Select results are summarized in Table 1. SS detected HbS percentages to 4.8% when HbF was low but not 6% HbS when Hb F is high. MS showed no HbF interference and identified HbS peaks (at 15837 amu) down to 3.1%. HbS percentages <3.1 were undetected by both methods. Conclusions Overall, MS was superior to SS for confirming HbS, particularly in samples with low variant percentage and/or elevated HbF. MS is also optimal when sample volume is minimal, such as for infants. Percentages of HbS <3% require methods such as IEF or DNA sequencing for confirmation.

Sickle cell disease in Australia: a snapshot from the Australian Haemoglobinopathy Registry.

Sickle cell disease (SCD) is the most common monogenic disorder worldwide. In deoxygenated conditions, the altered beta chain (haemoglobin S [HbS]) polymerises and distorts the erythrocyte, resulting in pain crises, vasculopathy and end-organ damage. Clinical complications of SCD cause substantial morbidity, and therapy demands expertise and resources. Optimising care for patients and planning resource allocation for the future requires an understanding of the disease in the Australian population. The Australian Haemoglobinopathy Registry (HbR) is a collaborative initiative of specialist centres collating and analysing data on patients with haemoglobin disorders. To provide a snapshot of SCD in Australia over a 12-month period based on data from the HbR. Patients with a clinically significant sickling disorder across 12 clinical sites were included for analysis. Data include demographic and diagnostic details, as well as details of the clinical management of the condition over a 12-month period. Data on 359 SCD patients demonstrate a shift in the demographic of patients in Australia, with a growing proportion of sub-Saharan African ethnicities associated with the HbSS genotype. Acute and chronic complications are common, and patients require significant outpatient and inpatient support. Prevalence of disease complications and therapeutic trends are in keeping with other high-income countries. This study provides the first national picture of SCD in Australia, describing the characteristics and needs of SCD patients, elucidating demand for current and novel therapy and facilitating the planning of services for this vulnerable population.

Changing Trends in Sickle Cell Disease-Related Mortality in the United States over Four Decades

Introduction: Sickle cell disease (SCD) causes significant morbidity and early mortality. The Cooperative Study of Sickle Cell Disease estimated median life expectancy for individuals with SCD at 42 years for males and 48 years for females in the early 1990s. However, this calculation was made prior to now standards-of-care in SCD, including routine transcranial doppler screening, pneumococcal prophylaxis, and the introduction of the primary disease-modifying therapy hydroxyurea and the widespread use of chronic blood transfusion. Over the last thirty years, with expanded access to disease modifying therapies, increased evidence exists for the preservation of organ function and less frequent acute vaso-occlusive pain. It remains unclear whether the introduction of these therapies has affected overall SCD-related mortality or the specific causes of death of those with SCD in the United States, particularly in the last decade when the use of hydroxyurea has expanded most significantly. Methods: We used the US mortality statistics for 1979-2020 available publicly through the CDC WONDER database (http://wonder.cdc.gov), which is a compilation of county, state, and national-level mortality statistics derived from death certificates, including age category at death, sex, race, ethnicity, year of death, underlying cause of death, and additional contributing causes using ICD-9 codes for 1979-1998 (282.6 sickle cell anemia- all SCD genotypes were included under one code in ICD-9) and ICD-10 codes for 1999-2020 (D57.0 sickle cell anemia with crisis; D57.1 sickle cell anemia without crisis; D57.2 double heterozygous sickling disorders; D57.8 other sickle cell disorders). We searched the SCD ICD-10 codes listed as underlying cause of death by five-year age groups for Black individuals and all ethnicities, (from Hamideh and Alvarez, Pediatric Blood and Cancer 2013) and compared the crude death rates overall and for each age group to those of 1999-2009. We also searched using the SCD ICD-10 codes included in “the multiple causes of death” to determine the 15 most common ICD categories of death in each 10-year period. Results: For the period 2010-2020, 5272 Black (Hispanic & non-Hispanic) individuals died in the United States with the underlying cause of death listed as one of the ICD-10 SCD codes (see Figure 1A for a map of the crude mortality rate distribution). The crude mortality rate was 1.1 per 100,000 Black individuals, which was significantly lower than the period 1999-2009 (crude rate 1.2 per 100,000, p < 0.0001) (Figure 1B). Of note, similar to prior trends, there is a significant increase in mortality rate in the 15-19 year age group versus 20-24 years (0.9 per 100,000 to 1.4 per 100,000, p < 0.0001) corresponding with the age of transition to adult centers. The mean age at death for all genotypes for 2010-2020 was 43 years (females: 44 years, males: 41 years) versus 39 years for 1999-2009 (females: 40 years, males: 38 years). For the period 2010-2020, 61% of cases listed SCD as the primary cause of death without specificity or proximal cause; for the other 39% of cases when an underlying cause of death was noted, cardiovascular disease was the most common (28%), followed by accidents (7%), cerebrovascular disease (7%), malignancy (6%), septicemia (4.8%), and renal disease (3.8%). The fifteen most common causes of death accounted for 90% of underlying causes of death listed in the SCD population. Conclusion: The sickle cell disease-related mortality rate has significantly declined over the last 40 years, including in the period 1999-2020, corresponding with the introduction of disease modifying therapies, improved SCD care, and decreased infant mortality. This overall improvement, however, provides contrast to the enduring sharp increase in mortality in the young adult years. This demonstrates the critical need to improve the transition process from pediatric to adult care and to emphasize the need for additional support for young adults after they transition to adult SCD care.

In-vitro Antisickling Activity of Pergularia daemia, Canna indica and Petiveria alliacea Plants used in the Treatment of Sickle Cell Anaemia in Edo State, Nigeria

Sickle cell disease is a genetic blood disorder that affects the shape and transportation of the red blood cells (RBCs) in blood vessels, leading to various clinical complications. Available medicines for treating the disease are insufficiently effective, toxic or expensive. Therefore, there has been a pressing need for effective and inexpensive therapeutic agents from indigenous medicinal plants. Petiveria alliacea, Canna indica and Pergularia daemia, respectively were evaluated for their cationic constituents as a measure for their antisickling activity in sickle cell anaemia disorder. The three medicinal plants were extracted separately with methanol solvent using maceration method for 72 hours. The extracts were concentrated using a rotary evaporator (Model RE, 200, USA). Phytochemical screenings were conducted using standard method, while other portions of the extract were subjected to dry ash digestion for determination of mineral elements by emission flame photometry (EFP) and atomic absorption spectrophotometry (AAS). Evaluation of the antisickling activity of the extracts was done using the sodium metabisulphite (SMBS) test. Eugenol, terpenoids and alkaloids were present in the three plant extracts, while K+ values recorded for Petiveria alliacea, Canna indica and Pergularia daemia were 54.30 mg kg–1, 180.10 mg kg–1 and 28.30 mg kg–1, respectively. Other mineral elements detected in the three plants were Cu2+, Zn2+, Fe2+ and Mg2+. The leaves extract of Canna indica and Pergularia daemia at high dose of 300 µg/mL caused significant reductions of sickle red blood cells from 15% to 6% and 15% to 1%, respectively at 90 minutes of the antisickling test. The research confirmed that extracts of both Canna indica and Pergularia daemia used in this study have significant antisickling properties in invitro studies than Petiveria alliacea.
 Keywords: Antisickling activity, Petiveria alliacea, Canna indica, Pergularia daemia, sickle cell, phytochemicals, minerals

S3313 Acute Sickle Intrahepatic Cholestasis From Sickle Cell SC Disease Causing Acute on Chronic Liver Failure

Introduction: Acute on Chronic Liver Failure (ACLF) is a disorder that results in grave systemic consequences. The dysregulated inflammatory response caused by an acute liver injury often results in multi-organ dysfunction. And while alcoholic/viral hepatitis or infections are common causes of ACLF, hematologic disorders are unusual. We present a case of ACLF due to sickle cell intrahepatic cholestasis from SC disease. Case Description/Methods: A 61-year-old man with history of HTN, sickle-cell trait, alcoholic cirrhosis presented for altered mental status. Initial labs showed TBili 30.7, DBili >20.0, AST/ALT 308/123, ALP 532 and INR 1.6. Phosphatidylethanol level negative. No new history of medication/herbal use, new sexual contacts, or drug use. Workup negative for hepatitis A/B/C/E. ANA negative, ASMA 26.7, IgG 2742. MRI Abdomen showed no liver mass with patent hepatic vasculature/biliary tree. LDH 531, Haptoglobin < 10, reticulocyte count 11.2, and Coombs test was positive. Hb electrophoresis showed 44.4% Hb C and 49.5% Hb S, consistent with SC disease. Hb was 8.5 (baseline), with no known crises since youth. Liver biopsy findings were consistent with sickle cell hepatopathy (sinusoidal dilation and congestion of sickled cells, ballooning degeneration of hepatocytes, and marked intracanalicular cholestasis). Patient had exchange blood transfusion (EBT) with improvement in Hb to 11.8 and decrease in retic count, LDH. Patient however continued to deteriorate, with increasing aminotransferases into thousands, worsening mental status, AKI, and coagulopathy. Patient made hospice care and eventually expired. Discussion: Hemoglobin SC (HbSC) disease is a less common form of sickle cell disease (SCD). Patients with HbSC disease have milder symptoms than SCD but more severe than sickle cell trait. Acute sickle hepatic crisis occurs in 10% of patients with SCD. Acute sickle intrahepatic cholestasis is the most severe form of sickle hepatopathy, associated with increased mortality. It is usually seen in SCD, but rarely in HbSC. Clinical presentation is more severe, with significant hyperbilirubinemia >15 mg/dL and aminotransferase elevations >1000 IU/L, reflecting ischemic injury. ALF/ACLF can evolve rapidly with multi-organ failure. EBT is considered in these situations. Non-responders have poor prognosis. Clinicians should be aware of the liver complications that can arise in patients with sickle cell-related disorders, including HbSC, particularly in patients with chronic liver disease.

M210 Hematological and biochemical differences in school going children with sickling disorder in steady state

M210 Hematological and biochemical differences in school going children with sickling disorder in steady state

A MATLAB model for diagnosing sickle cells and other blood abnormalities using image processing

&lt;span lang="EN-US"&gt;The conventional method for detecting blood abnormality is time consuming and lacks the high level of accuracy. In this paper a MATLAB based solution has been suggested to tackle the problem of time consumption and accuracy. Three types of blood abnormality have been covered here, namely, anemia which is characterized by low count of red blood cells (RBCs), Leukemia which is depicted by increasing the number of white blood cells (WBCs), and sickle cell blood disorder which is caused by a deformation in the shape of red cells. The algorithm has been tested on different images of blood smears and noticed to give an acceptable level of accuracy. Image processing techniques has been used here to detect the different types of blood constituents. Unlike many other researches, this research includes the blood sickling disorder which is epidemic in certain regions of the world, and offers a more accuracy than other algorithms through the use of detaching overlapped cells strategy.&lt;/span&gt;

End the pain: Start with antiracism.

End the pain: Start with antiracism.

Understanding the health-care experiences of people with sickle cell disorder transitioning from paediatric to adult services: This Sickle Cell Life, a longitudinal qualitative study

Background Transitions from paediatric to adult health-care services cause problems worldwide, particularly for young people with long-term conditions. Sickle cell disorder brings particular challenges needing urgent action. Objectives Understand health-care transitions of young people with sickle cell disorder and how these interact with broader transitions to adulthood to improve services and support. Methods We used a longitudinal design in two English cities. Data collection included 80 qualitative interviews with young people (aged 13–21 years) with sickle cell disorder. We conducted 27 one-off interviews and 53 repeat interviews (i.e. interviews conducted two or three times over 18 months) with 48 participants (30 females and 18 males). We additionally interviewed 10 sickle cell disease specialist health-care providers. We used an inductive approach to analysis and co-produced the study with patients and carers. Results Key challenges relate to young people’s voices being ignored. Participants reported that their knowledge of sickle cell disorder and their own needs are disregarded in hospital settings, in school and by peers. Outside specialist services, health-care staff refuse to recognise patient expertise, reducing patients’ say in decisions about their own care, particularly during unplanned care in accident and emergency departments and on general hospital wards. Participants told us that in transitioning to adult care they came to realise that sickle cell disorder is poorly understood by non-specialist health-care providers. As a result, participants said that they lack trust in staff’s ability to treat them correctly and that they try to avoid hospital. Participants reported that they try to manage painful episodes at home, knowing that this is risky. Participants described engaging in social silencing (i.e. reluctance to talk about and disclose their condition for fear that others will not listen or will not understand) outside hospital; for instance, they would avoid mentioning cell sickle disorder to explain fatigue. Their self-management tactics include internalising their illness experiences, for instance by concealing pain to protect others from worrying. Participants find that working to stay healthy is difficult to reconcile with developing identities to meet adult life goals. Participants have to engage in relentless self-disciplining when trying to achieve educational goals, yet working hard is incompatible with being a ‘good adult patient’ because it can be risky for health. Participants reported that they struggle to reconcile these conflicting demands. Limitations Our findings are derived from interviews with a group of young people in England and reflect what they told us (influenced by how they perceived us). We do not claim to represent all young people with sickle cell disorder. Conclusions Our findings reveal poor care for young people with sickle cell disorder outside specialist services. To improve this, it is vital to engage with young people as experts in their own condition, recognise the legitimacy of their voices and train non-specialist hospital staff in sickle cell disorder care. Young people must be supported both in and outside health-care settings to develop identities that can help them to achieve life goals. Future work Future work should include research into the understanding and perceptions of sickle cell disease among non-specialist health-care staff to inform future training. Whole-school interventions should be developed and evaluated to increase sickle cell disorder awareness. Funding This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 44. See the NIHR Journals Library website for further project information.

Growth Failure in Children with Sickle Cell Anaemia

Abstract:-  Background Sickle cell disease is a group of inherited sickling disorders consequent upon abnormalities of haemoglobin synthesis. It is one of the common causes of retardation in both physical growth and sexual maturation in children, as a result of chronic anaemia and consequent hypoxia that occur in several organs.  Objectives To determine the anthropometric indices (weight, height and Body Mass Index) of children with sickle cell anaemia (SCA) and compare them with that of children with normal haemoglobin; haemoglobin AA (HbAA).

Recommendations for Pregnancy in Rare Inherited Anemias

Rare inherited anemias are a subset of anemias caused by a genetic defect along one of the several stages of erythropoiesis or in different cellular components that affect red blood cell integrity, and thus its lifespan. Due to their low prevalence, several complications on growth and development, and multi-organ system damage are not yet well defined. Moreover, during the last decade there has been a lack of proper understanding of the impact of rare anemias on maternal and fetal outcomes. In addition, there are no clear-cut guidelines outlining the pathophysiological trends and management options unique to this special population. Here, we present on behalf of the European Hematology Association, evidence- and consensus-based guidelines, established by an international group of experts in different fields, including hematologists, gynecologists, general practitioners, medical geneticists, and experts in rare inherited anemias from various European countries for standardized and appropriate choice of therapeutic interventions for the management of pregnancy in rare inherited anemias, including Diamond-Blackfan Anemia, Congenital Dyserythropoietic Anemias, Thalassemia, Sickle Cell Disease, Enzyme deficiency and Red cell membrane disorders.

Clinical Course of Patients With Sickle Cell Anemia and Co-inherited Hematological Disorders: Experience at a Tertiary Hematological Centre.

To study the clinical course of patients with sickle cell anemia and coinherited hematological disorders. Retrospective analysis of clinical data of patients enrolled at our hospital over last 7years was performed. Eighty four patients of symptomatic sickling disorders were registered during this period, comprising of HbSS (n=49), HbS-β thalassemia (n=28), HbS-HbD disease (n=5), HbS-β thalassemia with G6PD deficiency (n=1) and HbS-hemophilia A (n=1). Among HbS-β thalassemia, 18% suffered from occasional pain crises and 27% required occasional blood transfusion. 40% patients with HbS-HbD disease required occasional blood transfusions, one patient was transfusion dependent, while none suffered from crisis episodes. Patient with HbS-β thalassemia with G6PD deficiency had increased transfusion requirement during first 3years of life, which decreased after that. Patient with HbS and severe hemophilia A had only one episode of severe bleeding, suffered from 1 crisis episode. In conclusion,HbA reduces severity of HbS in HbS-β+thalassemia. HbS-HbD disease can manifest as a transfusion dependent illness. HbSS reduces severity of G6PD deficiency after first few years of life. HbSS and hemophilia coinheritance ameliorates symptoms of hemophilia.

International Multi-Site Clinical Validation of Point-of-Care Microchip Electrophoresis Test for Hemoglobin Variant Identification

Introduction: Nearly 24% of the world's population carry hemoglobin (Hb) gene variants, with the large majority of affected births occurring in low-income countries. The most prevalent structural Hb variants are the recessive β-globin gene mutations, βS or S, βC or C, and βE or E1. Hb S mutation is prevalent in sub-Saharan Africa and in Central India. Hb C is common in West Africa, and Hb E is common in Southeast Asia and in India. Homozygotes or compound heterozygotes with βS (e.g., Hb SS or SC) have sickle cell disease (SCD), a chronic sickling disorder associated with pain, chronic multi-organ damage, and high mortality. While Hb EE causes only a mild microcytic anemia, Hb E in combination with β-thalassemia can lead to transfusion dependent thalassemia. Though carriers are typically asymptomatic, they may pass the mutations to their offspring. Screening is needed so that these disorders can be diagnosed early and managed in a timely manner2. For example, in low-income countries, due to lack of nationwide screening and comprehensive care programs, up to 80% of babies born with SCD are undiagnosed and less than half of them survive beyond 5 years of age2. The unmet need for affordable, portable, accurate point-of-care tests to facilitate decentralized hemoglobin testing in resource-constrained countries is well-recognized 2,3. Here, we present international multi-site clinical validation results and high diagnostic accuracy of the 'HemeChip' (Fig. 1), an affordable, 10-minute point-of-care microchip electrophoresis test for identifying common Hb variants S, C, and E. Methods: Institutional Review Board approvals were obtained at each study site, and blood samples were collected as part of the standard clinical care. Tests were performed by local users, including healthcare workers and clinical laboratory personnel. 315 children (6 weeks to 5 years of age) were tested in Kano, Nigeria. Study participants were enrolled at three hospitals, Amino Kano Teaching Hospital, Murtala Mohammed Specialist Hospital, and Hasiya Bayero Pediatric Hospital. 124 subjects (7 weeks to 63 years old) were included in the study at Siriraj Thalassemia Center in Bangkok, Thailand. 298 subjects (8 months to 65 years old) were tested at a referral testing facility of ICMR-National Institute of Research in Tribal Health, located at Late Baliram Kashayap Memorial Medical College, Jagdalpur, Chhattisgarh, India. Blood samples were tested with both HemeChip and the standard reference methods, high performance liquid chromatography or cellulose acetate electrophoresis. Reference test results were not available to the HemeChip users. Similarly, HemeChip test results were not available to the users of the standard reference tests. Clinical validation studies presented here were performed with a fully functional, portable HemeChip prototype developed at Case Western Reserve University (Fig. 1A). A commercial product has been developed based on this technology by Hemex Health Inc. under the product name, GazelleTM(Fig. 1B). Results and Discussion: Among the total 768 tests performed with HemeChip in all test sites, 732 were valid tests, as defined by the Standards for Reporting Diagnostic Accuracy (STARD)4. HemeChip correctly identified all subjects with Hb SS, Hb SC, Hb AS, Hb AE, and Hb EE with 100% accuracy (Table 1). Nine subjects with normal Hb (Hb AA) were identified as HbSS in Nigeria. No subjects with disease were identified as normal or trait by HemeChip. Three subjects with compound heterozygous Hb Sβ-thalassemia (2 subjects with Hb Sβ+-thalassemia, 1 subject with Hb Sβ0-thalassemia) were identified as Hb SS. Sensitivity was 100% for all Hb types tested. Specificity was 98.7% for Hb SS versus other Hb types, and 100% for all other Hb types tested. HemeChip displayed an overall diagnostic accuracy of 98.4% in comparison to standard reference methods for the Hb variants tested in all clinical testing sites (Table 1). HemeChip is a versatile point-of-care system that enables affordable, accurate, decentralized hemoglobin testing in resource-limited settings.

Risk factors for recurrent severe anemia among previously transfused children in Uganda: an age-matched case-control study

BackgroundIn resource-poor settings, transfused children often experience recurrence of severe anemia (SA) following discharge from hospital. This study determined the factors associated with recurrent severe anemia (RSA) among previously transfused Ugandan children aged less than 5 years.MethodsA case-control study was conducted in five hospitals in Uganda from March 2017 to September 2018. We prospectively enrolled 196 hospitalised children who had been transfused for severe anemia 2 weeks to 6 months prior to enrollment. Of these, 101 children (cases) were re-admitted with a hemoglobin [Hb] level of ≤6 g/dL and required transfusion; and 95 children (age-matched controls) were admitted for other clinical illness with a Hb > 6 g/dL. Children known to have sickle cell anemia, cancer, or bleeding disorders were excluded. Clinical and laboratory evaluation were done. Conditional logistic regression adjusted for age, was used to determine factors associated with RSA.ResultsThe median time (IQR) between the earlier transfusion and enrollment was 3.5 (1.9–5.7) months for cases, and was 5.0 (2.9–6.0) months for controls (p-value = 0.015). Risk factors (adjusted odds ratio, 95% confidence interval, and significance) for development of RSA were: hemoglobinuria (36.33, 2.19–600.66, p = 0.012); sickle cell anemia – newly diagnosed (20.26, 2.33–176.37, p = 0.006); history of earlier previous transfusions (6.95, 1.36–35.61, p = 0.020) and malaria infection (6.47, 1.17–35.70, p = 0.032).ConclusionMalaria chemoprevention, follow up visit for Hb check after discharge from hospital and sickle cell screening among previously transfused children represent practical strategies to prevent and identify children at risk for recurrent severe anemia. The cause of hemoglobinuria in children merits further investigations.

Genetics of Sickle Cell Anemia Disorders in Baghdad City, Iraq

The results show that the number of patients in Al-Iskan District surpassed that in Al-Harthiyya. Moreover, in studying the spread of Malaria disease and its relation to Sickle cell anemia, it has been noticed that patients infected with Malaria were more prone to have sickle cell anemia as in reflected in the high level of infected patients in Al-Iskan District. In investigation the relation between the patient's gender and this type of anemia, the study revealed that the number of male patients was lesser than of females in both Al-Iskan and Al-Harthiyya District. The study also revealed that majority of patients with sickle cell anemia are with in age group that ranges 11–25 years in Al-Iskan, While the results were different concerning Al-Harthiyya patients. The age groups that range 1–5 years as well as those 11–15 years are more infected with sickle cell anemia in the latter district.

Pregnancy Outcomes in Patients with Sickle Cell Syndromes Managed Antenatally with Exchange Transfusions: A Single Centre Analysis

Background/ObjectivesThe optimal management of pregnancy with sickle cell disease (SCD) is controversial (Cohen and O'Brien, Chapter 14, 2012). In particular, the value of prophylactic exchange transfusions in preventing complications from SCD and/or pregnancy itself is unclear. For the past decade at University College London Hospitals (UCLH), UK, we have undertaken prenatal exchange transfusions for most patients with sickle cell syndromes (SCS), HbSS, SC or Sb-thalassaemia. This is due to the poor outcomes we had experienced previously in a proportion of patients in whom prophylactic transfusion was not undertaken. We review the outcome over seven years in all such pregnancies managed at UCLH.Methodology/PatientsWe undertook a retrospective analysis of pregnancy outcomes of women with SCS delivering between 1 Jan 2011 and 31 Dec 2017. Data were collected from electronic hospital-held records. We recorded 50 pregnancies in 22 women, of which 25 resulted in live births. Most women had HbSS (82%), 14% had HbSC and 4% HbS-bthalassemia. The early pregnancy (<12 weeks) miscarriage rate of 28% was greater than the UK National Guidelines, 2012, which was 22% (Table 1). The median age (range) of our patients was 32 (19-40) years, which might contribute to the increased miscarriage rate. One woman sustained 6 of the 11 recorded miscarriages. Only 4% of pregnancies occurred in women >40, which is similar to national data for England (3.6%) (Centre for Maternal and Child Enquiries [CMACE], 2011). This age distribution is comparable to that in the population of Oteng-Ntim et al, 2015, who looked at pregnancy outcomes in a UK sickle population between 2010 and 2011. Patients were managed antenatally with exchange transfusions where there were no contraindications with respect to prior allo-immunisation, to reduce sickle related complications and improve pregnancy outcomes. Eight All patients were adequately hydrated antenatally. To gain insight into the effect of this management on maternal complications and fetal outcomes, these were compared with a recently reported cohort of SCS in London who did not receive exchange transfusions (Oteng-Ntim et al, 2015).ResultsPainful crises requiring admission antenatally were 9% compared with 17.6% reported by Oteng-Ntim et al, 2015. There were no admissions with sickle chest syndrome, either antenatally or postnatally, compared with 6.4% (Oteng-Ntim et al.). Preterm labour before 34 weeks' and 37 weeks' gestation occurred in one case (4.5%) and in 38% of cases, compared to 44.2% reported by Serjeant et al, 2004 and 47.1% reported by Oteng-Ntim et al before 37 weeks. There were no late miscarriages or stillbirths in our cohort. By contrast, in Oteng-Ntim et al, the stillbirth rate was 2.8% which is higher than the 0.92% reported in the general population (CMACE, 2011). The Caesarean section (CS) rate was 64%, which is higher than previously reported (39% in Barfield et al, 2010, 52.9% in Oteng-Ntim et al, 2015) (Table 3). One woman sustained a significant post-partum haemorrhage. The following complication rates were similar to those reported by Oteng-Ntim et al, 2015 (Table 3): postnatal pain: 18% vs 21.6%; pre-eclampsia 8% vs 7.8%; intrauterine growth restriction (IUGR): 22% vs 27.3% (Table 4). Four patients had pre-existing allo-antibodies, of whom three had two or more antibodies. No new allo-immunisations developed during pregnancy.ConclusionsAlthough our cohort numbers are small, they suggest a lower rate of painful crisis/chest syndrome than reported in series of SCS in which prophylactic exchange transfusions were typically not practised. While the rate of IUGR was lower than in historic reports, the difference was less clear than for painful crisis. There were no stillbirths in our series, despite the previously documented high incidence in women with SCS. The high rate of CS reflects local practice by clinicians wishing to avoid prolonged labour in this patient population. No serious adverse reactions to transfusion in pregnancy were seen despite one patient having had a previous hyperhaemolytic episode outside pregnancy. This study shows that prophylactic antenatal exchange transfusion is well tolerated and associated with fewer veno-occlusive crisis complications than historically reported with sickle disorders. Randomised studies are indicated in a larger cohort of patients to determine whether other benefits or risks accrue from this approach. [Display omitted] DisclosuresPorter:Cerus: Honoraria; Novartis: Consultancy; Agios: Honoraria.

A study on C-reactive protein as an early marker of vasococclusive crisis in sickle disorders

A study on C-reactive protein as an early marker of vasococclusive crisis in sickle disorders

Lived experienced of patients with sickle cell disease anemia about disease management (a qualitative research)

Introduction and Goal: Sickle cell disease (SCD) is a group of disorders, comprising sickle cell anemia and compound heterozygous disorders. It is the most common inherited hematological disease in the world. The objectives of this study were to describe the lived experienced patients with SCD during the evolution of a painful event and their solutions for control and manage it. We hope that with finding and cumulative of these solutions help patient with SCD for the management of their painful event. Materials and Methods: This qualitative study explored the experiences of sickle cell patients in management and control of pain and disease crisis in Iran. In-depth, unstructured individual interviews were conducted to extract the subjects' experiences of sickle cell patients in management and control of pain and disease crisis. Results: Codes extracted from the interviews led to the emergence of fore themes, which include implementation of various strategies to pain relief, awareness of pain intensifying, need to have the full support, awareness of the disease process. Conclusion: It is recommended that the instructions and programs written by nurses, be taught to patients and received feedback, to ensure that these strategies will be used.

Newborn screening for sickling and other haemoglobin disorders using tandem mass spectrometry: A pilot study of methodology in laboratories in England.

To determine (i) if electrospray mass spectrometry-mass spectrometry with the SpOtOn Diagnostics Ltd reagent kit for sickle cell screening could be integrated into the English newborn screening programme, under routine screening conditions, and provide mass spectrometry-mass spectrometry results which match existing methods, and (ii) if common action values could be set for all manufacturers in the study, for all assessed haemoglobins, to indicate which samples require further investigation. Anonymised residual blood spots were analysed using the SpOtOn reagent kit as per manufacturer's instructions, in parallel with existing techniques at four laboratories. Mass spectrometry-mass spectrometry instrumentation at Laboratories A and B was AB Sciex (Warrington, UK) AP4000, and at Laboratories C and D, Waters Micromass (Manchester, UK), Xevo TQMS and Premier, respectively. There were 23,898 results accepted from the four laboratories. Excellent specificity at 100% sensitivity was observed for haemoglobin S, haemoglobin C, haemoglobin E and haemoglobin OArab. A common action value was not possible for Hb C, but action values were set by manufacturer. The two haemoglobin DPunjab cases at Laboratory D were not detected using the common action value. Conversely, false-positive results with haemoglobin DPunjab were a problem at the remaining three laboratories. This multicentre study demonstrates that it is possible to implement mass spectrometry-mass spectrometry into an established screening programme while maintaining consistency with existing methods for haemoglobinopathy screening. However, one of the instruments investigated cannot be recommended for use with this application.

Anesthetic and Analgesic Effect of Neostigmine when Added to Lidocaine in Intravenous Regional Anesthesia

Background: Intravenous regional anesthesia (IVRA) has various advantages during short surgical procedures in upper and lower limbs, but one of its disadvantages is minimal postoperative pain relief. Aim of the study: To evaluate the anesthetic and analgesic effect of adding 1 mg neostigmine to 0.5% lidocaine in IVRA. Patients and methods: This randomized double blind controlled clinical trial was carried out at Assiut University Hospital after the approval of its Ethical committee and after obtaining an informed consent from all the patients. Eighty ASA I or II patients who were scheduled for elective hand and forearm surgery were included. We excluded patients with chronic pain syndrome, Reynaud disease, sickle cell anemia, diabetes, pregnancy, lactation, drug allergy and psychological disorders. Patients were randomly assigned to control group who received 3 mg/kg 0.5% lidocaine plus 1 ml normal saline in 40 ml volume and neostigmine group who received 3 mg/kg 0.5% lidocaine plus 1 mg neostigmine in 40 ml volume. Patients were assessed for onset and recovery from the sensory and motor blocks, postoperative pain, analgesic request and incidence of complications. Results No statistically significant differences were observed between groups as regards demographic data, anesthetic or analgesic criteria or the incidence of complications . Conclusion: Addition of 1 mg neostigmine to 0.5% lidocaine in IVRA has no anesthetic or analgesic effect, and there is no increase in the incidence of complications. There are no biological facts that support its use as adjuvant to local anesthetic agents in IVRA.