Sickle Solubility Test Research Articles

How Sensitive Is the Sickle Prep? Clinical Implications

Introduction The sickle cell solubility test, commonly known as “sickle prep” is a qualitative measure that relies on the property that deoxygenated hemoglobin S (HbS) is insoluble. Accordingly, blood samples drawn from individuals with circulating HbS appear cloudy when mixed with sodium hydrosulfite. 1 The sickle cell solubility test has been reported to be very sensitive (99%) and specific (99.9%) for detection of HbS. However, false negatives have been reported to occur in sickle cell disease (SCD) patients with severe anemia or high levels of hemoglobin F. 2,3 In those situations HbS levels may be very low and it remains unclear what level of HbS is required for the solubility test to be positive. To address this issue, we have examined the sickle cell solubility test in a cohort of SCD patients undergoing red cell exchange, acknowledging that in many of these patients, HbS levels fall below 15% when tested immediately after completing the exchange procedure. Methods 118 patients with sickle cell anemia were screened based on outpatient visits to the Inova Adult Sickle Center from January 1, 2023 - March 31 st, 2023. Of these, 6 patients were excluded from analysis due to lack of recent sickle cell solubility test during this period. Of the total number of patients included in the analysis (n=112), 25 (22%) underwent red cell exchange during this period. For each individual, the two most recent HbS percentages with the concurrently-determined sickle cell solubility result (positive or negative) were analyzed. We examined the data in the context of known genotype (HbSS, HbSC, HbSβ 0, HbSβ +positive). In patients undergoing red cell exchange, the most recent pre and post transfusion hemoglobin S percentage were collected. Results: 200 distinct HbS levels were collected and analyzed. Of those, 5/200 tested negative for the sickle cell solubility test, yielding an overall sensitivity rate of 98%. Of those 5 patients, 4/5 had received a red cell exchange during this period, and (1/5) had severe transfusion dependent anemia. Of those with a negative sickle cell solubility test, 4/5 patients had an SS genotype, and 1/5 had SC genotype. In patients who received red cell exchange, the sensitivity rate for the sickle cell solubility test is 84%. For all patient samples with HbS >15%, the sickle solubility test was 100% sensitive. However, among the 11 samples with HbS levels below 15%, 5 were sickle prep negative thereby indicating a reduced sensitivity (55%) below that threshold. Nine (9) out of the 11 samples were of patients who had undergone red cell exchange. Conclusion: The sickle cell solubility is a very sensitive measure to establish the presence of HbS, but must be interpreted with caution in those with HbS concentrations of <15%. Because it is readily available (typically resulted within an hour) it may be of benefit in emergency departments for patients for whom there is question about the validity of the sickle cell diagnosis. At our institution, this has been a valuable addition to the initial management of patients for whom medical records are not available and who present with apparent acute vaso-occlusive crisis. We do not propose withholding analgesia for patients with a reported history of sickle cell disease pending this test, but rather recommend its use as a confirmatory test for patients presenting with a reported history of this disease.

Significant haemoglobinopathies: A guideline for screening and diagnosis: A British Society for Haematology Guideline: A British Society for Haematology Guideline.

Antenatal screening/testing of pregnant women should be carried out according to the guidelines of the National Health Service (NHS) Sickle Cell and Thalassaemia Screening Programme. Newborn screening and, when necessary, follow-up testing and referral, should be carried out according to the guidelines of the NHS Sickle Cell and Thalassaemia Screening Programme. All babies under 1 year of age arriving in the United Kingdom should be offered screening for sickle cell disease (SCD). Preoperative screening for SCD should be carried out in patients from ethnic groups in which there is a significant prevalence of the condition. Emergency screening with a sickle solubility test must always be followed by definitive analysis. Laboratories performing antenatal screening should utilise methods that are capable of detecting significant variants and are capable of quantitating haemoglobins A2 and F at the cut-off points required by the national antenatal screening programme. The laboratory must ensure a provisional report is available for antenatal patients within three working days from sample receipt.

Status of Sickle Cell Disease Among Tharu Population In Banke District of Nepal.

Sickle cell disease (SCD) is prevalent in malaria-endemic areas because the gene for sickle cell provides its carrier with resistance against malaria. In Nepal, malaria is prevalent in Terai, hence the susceptibility of SCD is high in this region. Being indigenous to the Terai, thousands of people in the Tharu communities of the Banke districting Nepal are believed to have suffered from sickle cell disease. The objective of this study was to find out the status of sickle cell disease among the Tharu population of Banke district, Nepal. A cross-sectional, experimental study was performed among systematically randomly selected 275 samples from 3 Village Development Committee (VDCs). All the samples were first screened for the presence of sickle hemoglobin using the sickle solubility test method in Bheri Zonal Hospital. Then all sickle solubility positive samples were further processed for alkaline hemoglobin electrophoresis by using Interlab GenioS electrophoresis instrument. Out of a total 275 samples, 33 (12.0%) samples were confirmed as sickle solubility test positive. Among which, sickle cell trait was the most common disorder found grossing to 81.8%, followed by homozygous sickle cell disease; (15.2 %). One case (3.0%) of compound heterozygous sickle beta-thalassemia was also found.The Males were found to be more affected than females with ratio of 1.4:1.1. The highest frequency of SCD was found to be in 11-20 age groups comprising about 36.4%. Dangaura Tharu (51.5%) was the most common ethnic group with this disorder. The findings of this study indicate SCD is prevalent among the Tharu population in Banke district of Province-5, Nepal.

Correlation of HbF, HbA2, and HbS in sickle cell disease and its prevalence in Nigerian patients: A case series of 2 patients

Sickle cell disease (SCD) is the most common inherited disorder of hemoglobin worldwide. In Nigeria, the prevalence of SCD is 20–30/1000 live births. The burden of the disease has reached a level where it contributes 9–16% of the under-five mortality in many West African countries. This case series evaluated the chromatographic patterns and red blood cell indices of sickle cell homozygous patients. Red cell indices, blood film, sickle solubility test, and chromatographic patterns using Bio-Rad HPLC D10 were evaluated for both patients. Both the patients were Nigerian and HPLC showed HbS window 81.7 and 81.6% and increased HbF, that is, 7.5 and 8.8%. HbA2 was normal in both the cases, that is, 2.2 and 2.6%. Our data suggest that homozygous sickle cell disease is very common among the Nigerian population with an increase in HbF along with HbS and HbA2 is normal.

Association of Sickle Cell Trait on Career and Operational Outcomes in the United States Air Force.

Sickle cell trait (SCT) is a heterozygotic state defined by having one normal hemoglobin gene and one sickle hemoglobin gene. Individuals with SCT are at increased risk for negative health outcomes during intense physical exertion, especially in hot climates and high-elevation locations, or when dehydrated. The U.S. Air Force mitigates this risk through universal screening after accession followed by education of SCT-positive airmen. Airmen who are SCT positive but remain asymptomatic are not restricted in occupation choice or deployment/duty locations based on their SCT status. Previous studies have analyzed the relationship between SCT and health and fitness outcomes. The objective of this study was to analyze the relationship between SCT and career and operational outcomes in a large cohort of airmen and secondarily to analyze the relationship between hemoglobin S (HgbS) percentage and these outcomes. This is a retrospective cohort study of all recruits who entered U.S. Air Force (USAF) Basic Military Training (BMT) between January 2009 and December 2013. The SCT status was assessed through a sickle solubility test. Hemoglobin electrophoresis permitted subgroup analysis of SCT-positive individuals by HgbS percentage. The following career and operational outcomes were assessed: BMT graduation; retention at 4 and 6 years; promotion to the rank of staff sergeant by 4 and 6 years; overseas deployment and number of deployments within 6 years; and high-elevation assignment and cumulative months at a high-elevation assignment within 6 years. Multivariable logistic regression was used to assess all binary outcomes, controlling for age, sex, and race, to produce adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Multivariable Poisson regression was used to assess cumulative count outcomes and to produce adjusted incidence rate ratios (aIRRs) with 95% CIs. Attrition from BMT by SCT status was also assessed as a hazards function using the Kaplan-Meier approach with Cox proportional hazards. A total of 180,355 civilians entered USAF BMT during the 5-year surveillance period, of whom 169,837 graduated and had data available for analysis. Compared to their SCT-negative peers, SCT-positive airmen (n = 1,697) had 26% lower adjusted odds of promotion to staff sergeant within 4 years of BMT graduation (aOR = 0.74; 95% CI: 0.59-0.92) and served less time at a high-elevation assignment during their first 6 years (aIRR = 0.88; 95% CI: 0.85-0.91). The SCT status was not associated with statistically significant differences in BMT graduation, retention at 4 and 6 years, promotion to staff sergeant by 6 years, likelihood or number of overseas deployments, and likelihood of ever working at a high-elevation assignment. Retention at 4 and 6 years was inversely associated with HgbS percentage. SCT-positive and SCT-negative airmen had similar career and operational outcomes, with two exceptions: SCT-positive airmen were less likely to be promoted to staff sergeant within 4 years, and they spent less time at a high-elevation location during their first 6 years of service. The underlying explanation of these findings should be explored with an aim to support SCT-positive airmen and to reduce potentially unwarranted discrepancies. Efforts should continue to reduce the stigma associated with SCT.

Sickle solubility test to screen for sickle cell trait: what's the harm?

Sickle solubility test to screen for sickle cell trait: what's the harm?

Sickle solubility test to screen for sickle cell trait: what's the harm?

Sickle solubility test to screen for sickle cell trait: what's the harm?

Screening for sickle-cell trait at accession to the United States military.

Condition Definition SCT is a heterozygotic carrier state in which an individual has one copy of the normal HbA gene and one copy of the HbS variant. Commercial tests for SCT have been available since the early 1970s. The sickle solubility test qualitatively detects the presence of HbS by precipitating sickle hemoglobin in the presence of an oxygen depleting reagent. With a sensitivity approaching 99% and a specificity of 100%, sickle solubility provides an accurate screening method. The hemoglobin electrophoresis test is a confirmatory test that quantifies the percentage of HbS and is therefore able to distinguish among the HbS disorders, such as SCT or sicklecell disease. According to the 59th Clinical Lab Flight at Joint Base San Antonio-Lackland, Texas (oral communication, November 2013), the U.S. Air Force (USAF) spends $4.86 on the sickle solubility test and $9.41 on the hemoglobin electrophoresis test.

Potential pitfalls in the diagnosis of Hb Handsworth in areas with high prevalence of HbS

Hb Handsworth is a rare α-globin structural variant caused by a missense mutation either on the α2 or α1-globin gene (HBA2 or HBA1: c.55G>C, p.Gly18Arg). This variant might be erroneously diagnosed as HbS unless secondary confirmative tests are carried out. We encountered a child with a prominent peak eluting in the 'S' window on high-performance liquid chromatography (HPLC). Sickle solubility test, gel electrophoresis, and selective direct nucleotide sequencing of α1, α2, and β globin genes were performed on the patient's sample. In addition, previous HPLC results on a cord blood sample were retrieved. Sickle solubility test was negative. Gel electrophoresis revealed a band migrating at the S region with an extra faint band seen on acid gel electrophoresis. Molecular analysis of α2 globin gene revealed heterozygous state of Hb Handsworth. Hb Handsworth is a rare variant that can mimic HbS on HPLC. Failure to recognize this rare variant in regions where HbS is highly prevalent may result in serious misdiagnosis and subsequent incorrect genetic counseling.

Significant haemoglobinopathies: guidelines for screening and diagnosis

Antenatal screening/testing of pregnant women should be carried out according to the guidelines of the NHS Sickle Cell and Thalassaemia Screening programme. Newborn screening and, when necessary, follow up testing and referral, should be carried out according to the guidelines of the NHS Sickle Cell and Thalassaemia Screening programme. All babies under 1 year of age arriving in the UK should be offered screening for sickle cell disease. Preoperative screening for sickle cell disease should be carried out in patients from ethnic groups in which there is a significant prevalence of the condition. Emergency screening with sickle solubility tests must always be followed by definitive analysis. Laboratories performing antenatal screening should utilize methods capable of detecting significant variants and be capable of quantitating haemoglobins A 2 and F at the cut-off points required by the national antenatal screening programme. The laboratory must ensure a provisional report is available within three working days from sample receipt.

Sickle liver disease—An unusual presentation in a compound heterozygote for HbS and a novel β‐thalassemia mutation

A 38-year-old Ghanaian man presented with a 6-month history of worsening pruritus, jaundice, and ascites. He was previously fit and well and rarely drank alcohol. Screening tests for chronic liver disease including viral, autoimmune, and other metabolic causes including iron overload were unremarkable. A liver biopsy performed at the referring hospital demonstrated intralobular cholestasis and cirrhosis. He was listed for liver transplantation but subsequently developed sepsis with multiple organ failure and died. The sickle solubility test was positive. Blood smear showed cells consistent with liver failure and no sickle cells. Hemoglobin electrophoresis revealed HbA2 2.8%, HbF 0.5%, and HbS greater than HbA (49.6% vs. 41.3%) in the absence of blood transfusion. Sequence analysis of the beta-globin genes showed he was a compound heterozygote for the Hbs mutation at codon 6 (CAG --> GTG) and a novel mutation at position 844 of intron 2 (betaIVS2-844 C --> A). A diagnosis of sickle hepatopathy causing decompensated cirrhosis was made. This case is unusual insomuch as this patient was asymptomatic for over 35 years and represents a novel presentation of sickle cell disease. Sickle cell disease should be considered in appropriate patients when unusual presentations of liver disease arise.

Sickle cell disease: Recent advances

Diagnosis The term sickle cell disease encompasses several distinct genetic disorders, the most common of which is sickle cell anemia (homozygous sickle ceil disease or SS disease), which occurs in 1 of 450 black neonates. Somewhat less common are sickle cell-hemoglobin C (SC) disease and sickle cell-p thalassemia (S-p thalassemia, which includes both the p’ and p” variants). Sickle trait (which affects 8% of all African-Americans) is not considered a disease. The diagnosis of these conditions is based on history of disease complications, physical findings (jaundice, pallor, cardiac murmurs, splenomegaly), routine hematologic tests (hemoglobin, mean cell volume, peripheral blood smear), sickle solubility test, and hemoglobin electrophoresis or isoelectric focusing. A major advance during the past decade has been the widespread implementation in most states of neonatal screening programs, which have allowed sickle hemoglobinopathies to be diagnosed at birth and confirmed shortly thereafter. This fosters early education of parents and primary physicians. It also encourages implementation of preventive care practices, such as twice daily oral prophylactic penicillin and instructing parents to palpate the spleen. Neonatal screening programs now exist in