Acute Lymphocytic Leukaemia (ALL) is Primarily a Disease of Childhood - Case Study - Medical Science Assignment Help

Assignment Task

Leukaemia
Acute lymphocytic leukaemia (ALL) is primarily a disease of childhood accounting for 75% of childhood leukaemia (Arber et al., 2016). The majority of childhood ALL are of a B-cell phenotype (Huang et al., 2020), meaning they exhibit cell markers of an early precursor B-cell. B-cell acute lymphocytic leukaemia (B-ALL) are clonal growths of a precursor B-cell arrested at a particular stage of development (Arber et al., 2016). B-ALL occurs equally in males and females, with a peak incidence of between two and five years old (Gandhi et al., 2016). Generally, patients will present with organ involvement such as lymphadenopathy, hepatomegaly, splenomegaly and central nervous system (CNS) involvement. Features of bone marrow (BM) failure are also prominent, such as anaemia, neutropenia and thrombocytopenia (Arber et al., 2016). These symptoms usually have an abrupt onset, and speed in diagnosis is essential for ALL. The aetiology of ALL is unknown, but there is an increased risk with certain single nucleotide polymorphism (SNP) mutations in particular genes that lead to a deregulated cell cycle (Arber et al., 2016). There is also an increased risk of childhood ALL in those with constitutional genetic disorders such as Downs’s syndrome (Arber et al., 2016). Nearly all cases of B-ALL have clonal rearrangements of immunoglobin heavy chain (IGH) genes and cytogenetic abnormalities (Arber et al., 2016). B-ALL is subdivided into seven main categories associated with recurrent genetic abnormalities (Bhojwani et al., 2015). Those cases of B-ALL which do not possess any of these are classified as B-ALL NOS.
B-ALL has a good outlook, especially for children as there is an over 95% remission rate and an 80% cure rate (Arber et al., 2016). There is a 15% relapse rate for patients with B-ALL and this can be attributed to multidrug resistance (Huang et al., 2020). Treatment is usually divided into three main phases which consist of induction, consolidation and maintenance (Huang et al., 2020). This complex and aggressive cycle is to reduce the chances of relapse and provide a lifelong cure. There is a larger emphasis on CNS directed therapy, such as cranial prophylaxis, in ALL as it has shown to improve patient outcomes (Huang et al., 2020). Monitoring of minimal residual disease (MRD) throughout treatment is also effective in reducing relapse rates of B-ALL (Bhojwani et al., 2015). Despite the high rate of cure and improved therapy, ALL is still one of the leading causes of death in children with a tumour (Lo Nigro, 2013).
 

Presentation
A previously healthy, 2-year-old boy presented to the emergency room with a painful left hip after an accident on a trampoline. X-rays were done and a hip fracture was excluded. However, the pain persisted for over 2 weeks which lead to the routine full blood count (FBC) being done. The parents denied a history of fever, bruising, bleeding or pallor. The patient had no surgical history or medical issues prior to this hospital admission. He was on no medication and was fully immunised. There was no history of significant malignancies within the family to suggest an inherited cancer predisposition syndrome. Laboratory Findings
The FBC was performed on a whole blood EDTA anticoagulated tube using the Sysmex XN-10 analyser. The sample was checked for volume adequacy, correct labelling and presence of clots before being loaded onto the analyser. The analyser has quality control (QC) and maintenance checks are done daily, weekly and monthly to ensure accuracy of test results. The QC checks are done on a commercially made reagent called XN-check, with predetermined values. All these are recorded, and the documents are kept in a folder to ensure traceability. The Sysmex XN-10 also has the added XBar-M bulls moving average QC check to detect any shifts or trends within the daily sample testing. Delta checks are also present to flag abnormal results from patients who get regular tests. They are mainly there to detect mislabelling of samples or contaminated samples from being resulted. All reagents used on the Sysmex XN-10 are premade commercial reagents so, therefore, do not need calibration before being loaded onto the analyser. There are records kept of the lot number when the reagent is replaced. Staff loading samples onto the analyser and validating the results must be registered as a medical laboratory scientist or a medical laboratory trainee who has been assessed as competent. There must be standard operating procedures (SOP) available for all testing methods, safety measures and troubleshooting procedures performed within the laboratory. Laboratories that use the Sysmex XN analyser will be registered in an external quality assurance program where they receive samples for testing. These samples have known values and the aim of the program is to reduce variability of inter-laboratory results. The laboratories will report their result back to the program, which collate and review these to ensure standardisation between all participating laboratories. Laboratories will also go through internal audits performed by senior staff or quality managers. These will be done on a regular schedule, generally quarterly, or in response to a complaint. The laboratories will also undergo external audits by IANZ (International Accreditation NZ) to ensure the laboratory stays accredited which allows them to continue running.
The FBC results from the 17th (Table 1) indicated the presence of a neutropenia and an increase in reactive lymphocytes. Other than that, all parameters were considered normal for a 2-year-old male. At first glance, this could indicate a possible viral infection. When looking at the scatterplots (Figure 1), the WDF (white blood cell differential) channel was unable to separate the lymphocyte and monocyte cloud, thus forming a large grey undifferentiated cloud (Figure 1B). The cloud also extended upward on the side fluorescence scale triggering the atypical lymphocytes flag. The neutrophil cloud was also significantly smaller than would be in a normal WDF scatterplot (Figure 1B). The WNR (white cell and nucleated red blood cell) channel shows no presence of nucleated red blood cells (NRBC) (Figure 1D), also shown by the analysers count of 0.0 NRBC (Table 1). The PLT-O (optical platelet) channel scatterplot was normal (Figure 1C), also reflected by the normal platelet count of 266 and the normal platelet histogram spread (Figure 2B). All RBC counts were within the normal reference range for a two-year-old male, and the RBC histogram reflected this normality (Figure 2A). The analyser reflex tested reticulocyte parameters, which all appeared normal for the given reference ranges. The RETIC (reticulocyte) channel also showed a normal distribution on the scatterplot (Figure 1A). No delta checks were given as there was no recent history of a FBC done on this patient. A blood film was made due to the child being under five years old. This age trigger was chosen by the laboratory in review of best practice guidelines.
The medical laboratory scientist on shift reviewed the blood film and commented on the white blood cells (WBC). They indicated the presence of reactive lymphocytes with neutropenia, which caused them to suspect a viral infection. The film was referred to the haematologist as per best practice for a child with a possible viral infection. The haematologist reviewed the film two days later and noted a population of blasts. A new sample was collected and rerun on the Sysmex XN-10. Differences in counts from the 17th and the 19th of April are shown in Table 2. A new film was made and reviewed by the haematologist. Most parameters were similar, other than the lymphocyte and blast count. A manual differential was conducted and the population which was previously called reactive lymphocytes were now reclassified as a population of blast cells. The haematologist described a large monomorphic population of medium-sized circulating blasts with a high nuclear to cytoplasm ratio, round nuclear outline, relatively immature chromatin, and inconspicuous nucleoli (Figure 3). The cytoplasm was said to be lightly basophilic and did not contain azurophilic granules. The haematologist also commented that neutropenia was present with normal morphology. The findings were said to be highly suspicious of a diagnosis of ALL therefore was urgently referred to a specialist childhood haematology facility. PB and BM samples were taken for analysis by flow cytometry. The medical laboratory scientist who initially reviewed the blood film should have been able to pick up the presence of blast cells. They are a fully registered medical laboratory scientist and enrolled in multiple further education programs. Due to this mistake, the diagnosis was prolonged for two days, which is a problem as ALL diagnosis requires urgency. In the situation of suspected ALL, a haematologist is called and the slide is reviewed by them immediately, rather than sitting on a referral list. This highlights the importance of our role in the diagnosis of conditions that need urgent treatment.
For flow cytometry, peripheral blood or BM aspirate is collected in an EDTA tube, as heparin tubes can affect cell morphology (Barnett & Oldaker, n.d.). It is then transported immediately to the laboratory for testing. The sample must be transported at 15-25oC to maintain its integrity (Barnett & Oldaker, n.d.). Lipaemia, haemolysis or clots can cause a sample to be rejected for testing. As with the sysmex analyser, the testing carried out on the flow cytometer machine must be done by fully trained medical laboratory scientists. There will also be SOPs available for all steps of the testing and validation process. There may be yearly competency checks to ensure the staff retain the information they have learned during training. The equipment used must have daily QC checks done, with records of this kept for traceability. In flow cytometry reference beads are used as the QC checks. These have predetermined levels of fluorescence and should fall within a given channel range to ensure the test is running correctly and that accurate results can be obtained (Barnett & Oldaker, n.d.). All results of this are also plotted on a levy Jennings graph to detect shifts or trends over time. Biological controls can also be used as an internal QC. These are commercially made with a predefined target value (Barnett & Oldaker, n.d.). The biological controls can be used following the reference beads as an additional QC check. The biological control being used should have similar ranges of values to what the patient’s results may be. The flow cytometer instrument also must have records of daily, weekly and monthly maintenance. As with the Sysmex XN-10, laboratories with a flow cytometer will be enrolled in external quality assurance programs. The flow cytometer may also be assessed during internal audits performed by senior staff and external audits by IANZ to ensure accreditation.
In the PB, a population of 23% blast cells were identified. These cells were found to show positivity for CD10+, CD19+ and CD34+, with markedly weakened CD45 expression. CD34 is a precursor marker, indicating the malignant cells are immature blast cells. CD10 and CD19 are both B cell markers, with CD10 positivity only occurring at a transient stage of B cell maturation. CD45 is a common lymphocyte antigen present on all WBC but can be negative in ALL. These results were said to be highly suggestive of B-ALL. But this had to be confirmed with a full flow cytometry acute panel on a BM sample.
The flow cytometry done on the BM aspirate revealed a population of 83% blasts. These cells were gated by their low CD45 and SSC on the scattergram. The blast population was isolated and tested for CD markers using an acute panel (Table 2). The blast cells were shown to have over 90% positivity with the precursor cell markers HLA-DR, CD34 and TdT indicating the leukemic cell is immature, confirming it is a blast. The cells were also over 80% positive with CD19, CD10, CD22 and CD79a markers indicating the leukemic cell is of B-cell lineage. The absence of cytoplasmic IgM further confirms the immaturity of the leukemic cell. The blast population were also shown to be negative for myeloid markers (MPO, CD13, CD33, CD15), monocytic markers (CD64, CD14, CD11c), T-cell markers (CD3, CD2, CD7) and NK cell markers (CD56). Overall, the blast population was found to be consistent with the expected markers in B-ALL.
A BM aspirate was taken for a morphology review. On review, erythropoiesis was shown to be markedly reduced and had normoblastic maturation. Granulopoiesis was moderately suppressed with a marked left shift but normal morphology. Megakaryopoesis was markedly reduced but with normal morphology. Blasts were markedly increased in number, accounting for 88% of total nucleated cells. They were said to be small to intermediate in size with a high nuclear to cytoplasm ratio, open chromatin, and variable nucleoli. The cytoplasm was lightly basophilic without any granules and no Auer rods were seen. 'Hand-mirror' cells were frequently seen and an occasional osteoblast was noted. In conclusion, the morphology was said to be consistent with B-lymphoblastic leukaemia as confirmed by the preliminary BM aspirate flow cytometry.
Cytogenetic analysis was then performed showing the patient was hyperdiploid with a gain of chromosome X, 6, 8, 10, 14, 18 and 21. Hyperdiploid state is a common finding of childhood B-ALL, and it has a positive effect on patient prognosis (Arber et al., 2016). Fluorescent in-situ hybridisation (FISH) studies were complete in accordance with international best practice guidelines for cytogenetic testing. Paediatric FISH probes were used to target specific chromosome sequences. The patient was found to have no BCR/ABL, KMT2A (MLL) or ETV6/RUNX1 gene rearrangements. They did have a gain of two copies of the RUNX1 gene locus and a gain of two copies of chromosome 10 centromere. The number and quality of the cells examined were in accordance with the national pathology accreditation advisory council guidelines. CNS assessment was also performed at diagnosis for the assessment of CNS disease. This patient’s results were CNS 1 indicating an absence of blasts in the patient’s cerebrospinal fluid (CSF) (Kanwar, 2019). This is a good prognostic factor for the patient (Arber et al., 2016).
Clinical Outcome and Prognosis
Based on the flow cytometry results from the PB and BM aspirate, the patient was diagnosed with B-ALL. Due to the high cure rate of childhood ALL, treatment for this patient aims to establish a lifelong cure. The likelihood of a good outcome is further emphasised as the patient fits the majority of the variables leading to a good prognosis (Arber et al., 2016). These include factors such as the patient's hyperdiploid state, no CNS involvement present at diagnosis, between the ages of 2-10 years old, presenting with a relatively low white cell count and the fact he is caucasian. Radiation or stem cell transplant (SCT) may be used as a last resort in high risk patients who do not respond well to treatment (Pui & Evans, 2006), though all indications in this case point to this not becoming necessary. This patient will come in routinely for monitoring of MRD to assess whether the malignant population has been completely wiped out, or if more aggressive treatment needs to be given due to the persistent presence of the malignant population.

Over the past few decades, there have been large improvements in the outcome of childhood B-ALL due to multiple factors including better use of chemotherapy agents, the use of risk adapted therapy and the use of a CNS prophylaxis to prevent relapse where possible (Pui & Evans, 2006). This patient was placed in an open study called ALL1731 targeting patients with standard risk ALL. This study aims to identify patients within the standard risk group whose outcomes might be further maximised by the inclusion of an immunotherapy agent called blinatumomab (National Cancer Institute, 2019). Blinatumomab is a monoclonal antibody that targets CD19 expressed on the leukemic cells and is used in addition to chemotherapy (National Cancer Institute, 2019). It has the potential to alter the body's immune system and interfere with the malignant cells' ability to grow and spread (National Cancer Institute, 2019). The patient’s treatment will involve the use of the chemotherapy agent methotrexate. Chemotherapy drugs work in a variety of ways to halt the growth of cancer cells, including killing the cells, preventing them from dividing, and preventing them from spreading (National Cancer Institute, 2019). Combining the monoclonal antibody therapy with chemotherapy may work better for treating patients with B-ALL than with just combination chemotherapy alone.
 

Conclusion
A common first presentation of ALL is skeletal manifestations (Arber et al., 2016; Cohan et al., 2011). The pathogenesis for bone pain and fractures in ALL is a multifactorial effort by the massive proliferation of the leukemic cells in the medullary canal, the secreted products of the leukemic cells and an increased amount of osteoclast activating factor (Raj B K et al., 2020). The frequency of these manifestations, according to literature, ranges from 21-59% (Raj B K et al., 2020). Bone and joint pain are especially common in childhood B-ALL, and therefore a differential diagnosis of ALL must always be considered in young children presenting to the hospital with skeletal issues. A routine FBC of the patient should have been done immediately once the hip fracture was excluded. The fact it took almost a month for this routine test to be completed could lead to a worse outcome for the patient due to prolonged diagnosis time. Speed of diagnosis is essential when it comes to ALL due to their aggressive nature and potential CNS involvement. This case highlights the importance of the routine test done within the haematology laboratory. The FBC is a quick and easy test, with little cost to the hospital and little risk to the patient, therefore it must be utilised whenever possible.
 

Introduction
Haemoglobinopathies are inherited disorders of the globlin protein and they are the most common genetic defect globally (Trent, 2006). Mutations in the globin gene that lead to the production of abnormal proteins are called haemoglobin (Hb) variants (Trent, 2006). A common Hb variant is HbS, and this occurs due to a single nucleotide polymorphism (SNP) in the ?-globin gene causing the substitution of valine for glutamic acid in the sixth position of the ?-globin chain (Gladwin et al., 2019). In hypoxic conditions, the amino acid change results in the formation of sickled red blood cells (RBC). Because valine is non-polar and glutamic acid is polar, it influences how Hb molecules interact with one another (Gladwin et al., 2019). When HbS is fully oxygenated, the quaternary structure of the Hb molecules remains soluble, just like HbA, and the RBCs retain their normal biconcave disc shape (Randolph, 2016). However, due to allosteric changes when the cell is deoxygenated, valine is exposed (Randolph, 2016). This reduces the solubility of HbS molecules and enables adjacent HbS molecules to form bonds (Randolph, 2016). Sickling arises when the HbS polymers grow to a length greater than the diameter of the RBC.
Sickle cell disease (SCD) refers to a group of patients who inherit mutations in ? -globin genes that result in a similar clinical syndrome. SCD is one of the most common forms of haemoglobinopathies. Those homozygous for HbS are diagnosed as suffering from sickle cell anaemia (SCA), the most severe form of SCD. SCA is an inherited disorder with a high mortality rate and increased prevalence among those of African ancestry. This is because the prevalence of SCA corresponds to areas where malaria is endemic. The sickle cell trait provides a selective advantage against malaria as well as protection against plasmodium species that infiltrate RBC.
The pathophysiology of SCA is induced by sickled RBCs, which are ridged and restrict blood flow within limbs or organs. The decreased blood flow is exacerbated by increased plasma viscosity caused by chronic haemolysis of sickled cells. Reduced blood flow prolongs the exposure of HbS-containing erythrocytes to hypoxic conditions, promoting more sickling formation. Vaso-occlusive complications can emerge because sickle cells can enter the microvasculature in a biconcave disc conformation when oxygenated and then become deformed and viscous when deoxygenated, transforming to the sickle cell configuration in the vessel and becoming mechanically sequestered. The degree of intracellular hydration influences the sickling process as well. Psickle, a membrane channel that is normally inactive, is opened by polymerised deoxy-HbS. The outflow of ions and water lead to intracellular dehydration. This increases the intracellular concentration of HbS and intensifies polymerization. The redistribution of phospholipids in the RBC membrane also has an important role in SCA pathophysiology. Phospholipid on the exterior surface of RBCs binds thrombospondin on vascular endothelial cells, enhancing adherence between RBCs and the vessel wall and leading to vaso-occlusive crisis, activation of coagulation, and decreased RBC survival.
 

Presentation
A 9-year-old East African girl presented to the hospital with fatigue, a fever of over 38oC, and leg/arm pain. On examination, she was jaundiced, dehydrated and febrile. Neither of her parents had a known history of any haemoglobinopathies. This triggered a laboratory investigation to be performed.
 

Laboratory Findings
SCA is associated with many biochemical abnormalities. This can be seen reflected in the patient’s general chemistry results (Table 1). Of importance included her raised bilirubin, aspartate amino-transferase (AST), alanine aminotransferase (ALT) and lactose dehydrogenase (LDH) levels. All of which are important markers for intravascular haemolysis. Total bilirubin levels are a sign of chronic haemolysis, and this caused her jaundiced appearance upon arrival at the hospital (Pandey et al., 2012). The AST:ALT ratio is also an important haemolytic marker, this is as it increases as the Hb level decreases (Pandey et al., 2012). These results will always be raised in a patient with SCA, whether suffering a crisis or in a steady-state, because of the underlying haemolysis constantly occurring (Pandey et al., 2012). LDH, which can also be used as a marker of haemolysis (Kato et al., 2017), also showed a large increase. Though LDH does have limitations as a marker of haemolysis because it is released by any tissue experiencing lytic damage (Kato et al., 2017), and this is often occurring in SCA patients. Overall, these results reflect the patient is currently suffering from a haemolytic crisis. Other biochemistry results can reflect bone or organ damages, which are common in SCA. The patients raised alkaline phosphatase can indicate bone damage due to the accelerated haemopoiesis and bone infarctions associated with SCA (Pandey et al., 2012). Total protein and globulin levels were raised which is usually associated with SCA. This is as the disease causes structural and functional damages to the kidneys and liver (Pandey et al., 2012). The higher the levels, the more severe the organ dysfunction. These can be confirmed by further liver and renal function tests. Hepatic dysfunction can also be furthered by the presence of bilirubin gallstones in SCA patients (Pandey et al., 2012).
 

QC for FBC
Her full blood count (FBC) tests were done on the Sysmex XN-20 analyser using an EDTA anticoagulated tube and reported onto the computers IT-3000 system. Her results are shown in Table 2. Her FBC revealed relatively normal White Blood Cell (WBC) parameters, other than a monocytosis. This normality of her WBCs were reflected by the normal population sizes and arrangements within the WDF (WBC differential) scatterplot (graph). The FBC revealed a slight thrombocytosis but the morphology appeared normal on the PLT-F (Platelet fluorescence) scatterplot (Graph). The platelet (PLT) histogram was slightly abnormal toward the tail of the peak. It wasn’t smooth indicating the possible presence of giant PLTs and RBC fragments which can both found in SCA patients. Her RBC parameters were very abnormal and suggestive of a possible haemoglobinopathy. She had a raised Hb and haematocrit (Hct), but a normal RBC count. The mean cell volume (MCV) was normal but the slight increase in her mean cell haemoglobin (MCH) indicated a slight microcytic anaemia. There was a significant increase in the RBC distribution width (RDW), also reflected on the RBC histogram as an enlarged base of the peak. This indicates anisocytosis might be present. Reticulocytosis was present, and this was also reflected in the reticulocyte (RETIC) scatterplot. The increased reticulocyte cloud size, especially in the immature reticulocyte fraction (IRF) population indicate a bone marrow (BM) response to possible chronic haemolysis. The FBC indicated the presence of nucleated RBCs (NRBC), reflected on the white cells and nucleated red cells (WNR) scatterplot as a small population next to the WBC cloud. This area is usually blank as any amount of NRBCs are considered abnormal. This FBC finding automatically triggered a film to be made by the SP-10 machine. The slide went through Cellavision and was reviewed by a medical laboratory scientist.
The medical laboratory scientist commented on the film, saying there were many sickle and polychromatic cells present. They also noted the PLTs and WBCs had normal morphology. The film was then referred to the haematologist. The haematologist commented on the presence of sickle cells, RBC fragments, polychromasia, howel-jolly bodies and NRBCs (Figure 3). This is consistent with a haemoglobinopathy, likely HbS disease, so the haematologist requested a haemoglobinopathy screen. EDTA samples were collected from the patient and sent off to specialised laboratories for these studies.
A haemoglobinopathy screen consists of high performance liquid chromatography (HPLC) as the primary screening method, followed by secondary testing based on the result of the HLPC screen. In this case, the HLPC indicated the presence of HbS so a sickling test was done. A Glucose-6-phosphate dehydrogenase (G6PD) screen was also conducted to rule out a coexisting deficiency, which increases the likelihood of a haemolytic crisis. The G6PD screen may have been done as it is a common deficiency throughout sub-Saharan Africa and resents with similar symptoms to SCA patients experiencing a crisis.
HLPC is the process in which a mixture of molecules with a net positive charge are separated by their absorption onto a negatively charged stationary phase in a chromatography column, followed by their elution in a mobile phase. The Hb fractions will separate based on their ionic interaction with the cartridge. The separated fractions pass through a flow cell, where absorbance is measured. Changes in absorbance are monitored and displayed in a chromatogram. For each normal and variant Hb, the system has a characteristic period of time, referred to as the retention time, before the Hb appears to elute. Staff operating the HLPC machine must be fully trained medical laboratory scientists and must be enrolled in the CPD programs. Standard operating procedures for the HPLC testing process, result interpretation and troubleshooting procedures must be readily available. Before every batch of testing is done on patient samples the machine must run the quality control (QC) samples. These will include a normal QC sample, which mimics a normal patients Hb content, and an abnormal QC sample. This contains Hb that will eluate with HbA, HbF, HbS and HbC, and is often called AFSC control. If these QC samples get the expected results then patient samples may begin to be tested. Documentation of the QC results and reagent lots used must be kept for traceability. The laboratory will also be enrolled in quality assurance programs where they ….. internal/external QA.
Her HLPC showed her HbF levels to be increased to 4.7% (normal 0-0.1%), her HbA2 levels to be increased to 4.9% (normal 2.2-3.2%). The peak at HbS was quantitated at greater than 85% and no HbA was present. This is reflexive of a HbSS patient as no normal beta chains are able to be produced, therefore no HbA will be present. Due to HbS being a terrible oxygen transported patients with HbSS will have increased HbF and HbA2 above the reference range as compensation mechanisms. The sickling test was carried out as the patient had an abnormal chromatographic Hb fraction in the position of HbS. This test is done to demonstrate the presence of HbS, and this is done by inducing sickle cell formation by depriving the cells of oxygen. A drop of blood is mixed with sodium metabisulphite and sealed between a glass slide and a coverslip. Sodium metabisulphite reduces the oxygen tension further aiding the typical sickle shape to form. The red cells are then observed under the microscope at different time periods to look for presence of the sickling. A normal patient sample is run alongside the test patient as a negative control. At both the one hour and two hour mark, the patient showed positive for sickled cells under the microscope. The findings of the haemoglobinopathy screen along with other haematology and chemistry laboratory findings indicate she is homozygous for HbS and were diagnosed with symptomatic SCA. The principle of a G6PD screen focuses on the inability to reduced NADP to NADPH in G6PD deficient patients. The NADPH levels are measured under Ultraviolet light as it can fluoresce. A normal patient will have a high fluorescent, which would be checked against a positive control. The patients G6PD results displayed normal fluorescence excluding the presence of homozygous deficient G6PD. As the inheritance is sex-linked, in females a normal screen test doesn’t exclude heterozygote carriers and if clinically indicated further enzyme assays may need to be done. In this case, no further testing was needed. The findings of the haemoglobinopathy screen along with her other haematology and chemistry laboratory findings indicate she is homozygous for HbS. She was diagnosed with symptomatic SCA.
Iron studies were also performed to rule out the presence of a coexisting iron deficiency anaemia which is common in SCD patients due to the chronic haemolysis. Her iron studies appear normal (Table 3), but she must be monitored throughout her life to ensure she does not become iron deficient.
Clinical Outcome and Prognosis
Most therapies for SCA patients are focused on symptom management. Generally, all patients are encouraged to avoid factors known to causes crises. They are asked to stay hydrated, take folic acid supplements, avoid anoxic environments, have general good hygiene, proper nutrition, and avoid adverse weather conditions. Most are given prophylactic oral penicillin to avoid infection. Completion of the required vaccinations are highly encouraged for SCA patients during childhood as it reduces the chances of infection, in addition, annual administration of influenza vaccine is recommended.
As per recommended management guidelines the patient was prescribed folic acid, hydroxycarbamide and amoxicillin. Folic acid and amoxicillin are given prophylactically to reduce more severe clinical presentations of SCA. Folic acid is given to SCA patients to reduce the likelihood of suffering an aplastic crisis. An aplastic crisis will occur due to an infection with parvovirus or from folate deficiency, they are characterised by a sudden fall in Hb and reticulocytes due to BM suppression. It is a common, life-threatening complication of SCA and usually requires a blood transfusion. Amoxicillin is a prophylactic oral penicillin antibiotic that SCA patients are often prescribed to reduce the likelihood of a bacterial infection. Bacterial infections are a common finding in SCA and are a common cause of mortality and morbidity. The patient’s vaccination records indicated she was up to date on her vaccinations, as recommended for the management of SCA. The patient was also found to be hyposplenic due to damage caused by vaso-occlusive crisis that diminish splenic tissue and replace it with scar tissue. This causes a decrease in function and is a common finding in SCA patients, which further increases your risk of life-threatening bacterial infections. Hydroxyurea is known to increase the proportion of HbF in the RBC, which in turn reduces symptoms and prolongs the lives of SCA patients. Because HbF does not copolymerize with HbS, if the production of HbF can be sufficiently augmented, the complications of SCD can be avoided. Hydroxyurea is also known to increase Hb and MCV which has shown to improve favourable outcomes in SCA patients. Another favourable response of treatment is that it does not only reduce the expression of adhesion molecules, but also decreases the number of receptor proteins located on endothelial cells. Therefore, hydroxyurea decreases vascular adhesion which contributes to a decreased number of vaso-occlusive crises.
Throughout the patient’s life, they will be in and out of the hospital due to common complications of SCA, or just for check-ups to monitor treatment and drug compliance. The hallmark of SCD is vaso-occlusive crisis, which accounts for most hospital and emergency department visits. This acute, painful manifestation of SCD occurs with high predictability and intensity in many people and can be precipitated by acidosis, hypoxia, dehydration, infection and fever, and exposure to extreme cold. Most vaso-occlusive crisis events occur in capillaries and post-capillary venules. The number of painful episodes per year ranges from none to six. In the lungs, pulmonary infarction from sickling in the microvasculature causes acute chest syndrome. Acute chest syndrome is characterized by fever, chest pain, and the presence of pulmonary infiltrates on the chest radiograph and is the leading cause of death among adults with SCD. Treatment for vaso-occlusive crisis and acute chest syndrome episodes is treated by rest, warmth, rehydration and antibiotics. Analgesia at the appropriate level for pain should be given. A non-steroidal anti-inflammatory agent and opiates for when the pain becomes chronic. Blood transfusion is given if there is very severe anaemia with symptoms or with impending critical organ complications. Exchange transfusion may be needed, particularly if there is neurological damage or repeated painful crises. Haemolytic crisis are also common complications of SCA caused by the continuous destruction of RBCs within the circulation. This perpetuates the chronic haemolytic anaemia and autosplenectomy effect.
SCA also has the ability to cause all sorts of end-organ damage for the patients. These include, but are not limited to retinopathy, priapism, chronic liver damage due to microinfarcts and pigment gallstones, microstrokes causing central nervous system dysfunction, myocardial ischemia, biventricular dysfunction and cardiomegaly. Cardiomegaly can develop in patients with severe anaemia as the heart works harder to maintain appropriate blood flow and tissue oxygenation.
 

Conclusion
Proper SCD management has increased patients' life expectancy from 14 years in 1973 to the present average life span of 50 years (rodak). Some patients can even survive into their seventh decade of life (Division of Blood Diseases and Resources, 2002). They can live long and fulfilling lives but they are discouraged from jobs that require strenuous physical exertion or exposure to high altitudes or extreme environmental temperature variations (Division of Blood Diseases and Resources, 2002). Screening newborns for hemoglobinopathies has resulted in a considerable reduction in mortality in children with SCD. It allows for timely diagnostic testing, and implementation of parental education, prophylactic penicillin and comprehensive care (Division of Blood Diseases and Resources, 2002). Comprehensive care includes ongoing patient and family education about disease complications and treatment, disease specific health maintenance services, access to timely and appropriate treatment of acute illness, genetic counselling, and psychosocial support (Division of Blood Diseases and Resources, 2002). Certain complications surrounding pregnancy are more likely to occur in SCA patients. During pregnancy, patients are more likely to suffer from hypertension and have increased percentages of preterm births when compared to pregnant woman without SCA (Division of Blood Diseases and Resources, 2002). Prenatal care for women with SCA must focus on close monitoring, along with prompt diagnosis and aggressive treatment of complications during the prenatal and neonatal period (Division of Blood Diseases and Resources, 2002). This will aid in better outcomes for both the mothers and neonate during SCA pregnancies.

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