sickle cell anemia hesi case study quizlet

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Case Study: Sickle Cell Disease A 25-Year-Old in Transition

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A 25-year-old woman with a history of sickle cell disease (SCD) presents to the clinic for follow-up after a hospitalization for a vaso-occlusive pain crisis complicated by influenza A. She has a history of an acute ischemic stroke at age 5 years and has received monthly, simple red cell transfusions since the stroke. Her last transfusion was approximately four months prior. She is taking deferasirox 20 mg/kg daily but occasionally misses doses.

Laboratory results show the following:

Which of the following is the next best step in diagnosis

• Restart scheduled red blood cell transfusions
• Start prophylactic penicillin
• Discontinue transfusions and start hydroxyurea
• Order transcranial doppler ultrasonography (TCD) to assess risk of stroke
• Increase dose of deferasirox to 25 mg/kg/day

Explanation

The incidence of primary stroke in children with SCD is 0.6 to 0.8 events per 100 patient-years, with a cumulative incidence of 7.8 percent by age 14 years in the Jamaican cohort and 11 percent by age 20 years in the U.S. Cooperative Study of Sickle Cell Disease. Once stroke has occurred, the incidence of recurrent (secondary) stroke ranges from 47 to 93 percent in patients not started on regular transfusions. The Stroke Prevention Trial in SCD (STOP) randomized 130 high-risk children with SCD to either transfusion therapy (to maintain HbS 30%) or observation. These high-risk children had an increased blood flow in the internal carotid or middle cerebral artery by TCD. This study showed a 92 percent reduction in incidence of first stroke in transfused high-risk patients. A follow-up study, STOP2, randomly assigned 72 children whose TCD had normalized after 30 months of transfusion therapy to either ongoing or discontinued transfusions. The study was closed early due to a significant increase in abnormal TCD velocity and stroke risk for those who halted transfusion therapy.

The multicenter phase III TWiTCH trial evaluated children with SCA and abnormal TCD velocities without a history of stroke on chronic transfusions. Data showed that hydroxyurea at maximal tolerated dose was noninferior to chronic transfusions for maintaining TCD velocities as primary stroke prophylaxis (choice C). This patient has a history of ischemic stroke, so the results of TWiTCH do not apply to her.

The Stroke with Transfusions Changing to Hydroxyurea (SWiTCH) study was designed as a phase III multicenter trial to determine the efficacy of hydroxyurea/phlebotomy, compared with transfusions/chelation for children with SCA, stroke, and iron overload in secondary stroke prophylaxis. The primary endpoint was a composite of noninferiority for stroke prevention and superiority for reduction of liver iron content. The trial was terminated at the first scheduled interim analysis for futility for the composite endpoint, which required superiority of phlebotomy over iron chelation for reducing excess iron stores. The incidence of stroke on the hydroxyurea plus phlebotomy arm was higher (7 of 67 patients; 10.4%) than in the transfusion plus chelation arm (1 of 66 patients; 1.5%). These results, though not powered for inferiority, showed a trend towars increased stroke risk with transition to hydroxyurea. In patients with prior stroke, cessation of transfusion therapy is currently not recommended.

Whether chronic transfusion therapy can be stopped after a longer period of transfusions in a patient with a prior stroke remains unclear even though risk of recurrent stroke remains high in adolescence and young adulthood. In patients older than 16 years, TCD velocity criteria to determine stroke risk is not reliable (choice D).

In the Prophylaxis with Oral Penicillin in Children with Sickle Cell Anemia trial, children with SCA were randomly assigned to receive oral prophylactic penicillin or placebo PROPS 1986 ). The trial ended eight months early after the occurrence of 15 cases of pneumococcal sepsis, 13 in the placebo group and two in the penicillin group, showing an 84 percent reduction in pneumococcal sepsis with penicillin prophylaxis. The follow-up study, PROPS II, did not show an increased risk in pneumococcal infections with discontinuation of prophylactic penicillin after age 5 years. Therefore, prophylactic penicillin is not recommended in adults with SCA (choice B).

The trajectory of ferritin in this patient has not been established and an increase in oral iron chelation is not indicated at this time.

Case Study submitted by Marquita Nelson, MD, of University of Chicago, Chicago, IL.

• Hirst C, Owusu-Ofori S Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease . Cochrane Database Syst Rev. 2014 6:CD003427.
• Valadi N, Silva GS, Bowman LS, et al Transcranial Doppler ultrasonography in adults with sickle cell disease . Neurology. 2006 22:572-574.
• Ware RE, Davis BR, Schultz WH, et al Stroke with transfusions changing to hydroxyurea (SWiTCH) . Blood. 2012 119:3925-3932.
• Kumar N, Gross JB Jr, Ahlskog JE TCD with transfusions changing to hydroxyurea (TWiTCH): hydroxyurea therapy as an alternative to transfusions for primary stroke prevention in children with sickle cell anemia . Blood. 2015 126:3.

American Society of Hematology. (1). Case Study: Sickle Cell Disease A 25-Year-Old in Transition. Retrieved from https://www.hematology.org/education/trainees/fellows/case-studies/sickle-cell-disease-a-25-year-old-in-transition .

American Society of Hematology. "Case Study: Sickle Cell Disease A 25-Year-Old in Transition." Hematology.org. https://www.hematology.org/education/trainees/fellows/case-studies/sickle-cell-disease-a-25-year-old-in-transition (label-accessed June 29, 2024).

"American Society of Hematology." Case Study: Sickle Cell Disease A 25-Year-Old in Transition, 29 Jun. 2024 , https://www.hematology.org/education/trainees/fellows/case-studies/sickle-cell-disease-a-25-year-old-in-transition .

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Sickle Cell Anemia Case Study Hesi

Embarking on a journey into the realm of sickle cell anemia case study hesi, we delve into the complexities of this genetic condition, exploring its clinical manifestations, pathophysiology, diagnosis, treatment, and nursing management. Join us as we unravel the intricacies of sickle cell anemia and its impact on patient care.

Sickle cell anemia, an inherited blood disorder, affects millions worldwide, presenting unique challenges for healthcare professionals. This case study will provide a comprehensive overview of the condition, equipping you with the knowledge and understanding necessary to provide optimal care to affected individuals.

Overview of Sickle Cell Anemia

Sickle cell anemia is a genetic blood disorder characterized by the presence of abnormal hemoglobin, known as hemoglobin S (HbS). This abnormal hemoglobin causes red blood cells to become sickle-shaped, leading to a range of clinical manifestations.

Genetic Basis

Sickle cell anemia is an autosomal recessive disorder, meaning that both copies of the gene responsible for producing hemoglobin must carry the mutation for the condition to manifest. The mutation responsible for HbS is a single nucleotide change in the beta-globin gene, which leads to the substitution of glutamic acid with valine at the sixth amino acid position of the beta-globin chain.

Clinical Manifestations

The clinical manifestations of sickle cell anemia vary widely and can include:

• Chronic anemia
• Episodes of acute pain (vaso-occlusive crisis)
• Organ damage (e.g., stroke, heart failure, kidney disease)
• Delayed growth and puberty
• Frequent infections

Epidemiology

Sickle cell anemia is most common in individuals of African descent, with an estimated global prevalence of 0.15%. The highest prevalence is found in sub-Saharan Africa, where it affects up to 2% of the population. The prevalence of sickle cell anemia is also significant in certain regions of India, the Mediterranean, and the Middle East.

Pathophysiology of Sickle Cell Anemia

Sickle cell anemia is an inherited blood disorder characterized by the production of abnormal hemoglobin, the oxygen-carrying protein in red blood cells. This abnormality leads to the formation of sickle-shaped red blood cells, which have a reduced ability to carry oxygen and can cause a variety of complications.

Molecular Basis of Sickle Cell Anemia

The molecular basis of sickle cell anemia is a mutation in the beta-globin gene, which codes for the beta-globin chain of hemoglobin. The mutation results in the substitution of a single amino acid, valine, for glutamic acid at position 6 of the beta-globin chain.

This substitution alters the shape of the hemoglobin molecule, causing it to polymerize and form long, rigid fibers within red blood cells.

Formation of Sickle-Shaped Red Blood Cells

Under conditions of low oxygen tension, such as during exercise or stress, the hemoglobin fibers polymerize and cause the red blood cells to assume a sickle shape. These sickle-shaped cells are less flexible than normal red blood cells and have difficulty passing through small blood vessels.

As a result, they can become trapped in the microcirculation, leading to blockages and a reduced supply of oxygen to tissues.

Consequences of Sickle-Shaped Red Blood Cells

The consequences of sickle-shaped red blood cells can be severe. They include:

• Painful episodes (vaso-occlusive crises): Sickle-shaped cells can block blood flow to organs and tissues, causing severe pain.
• Anemia: Sickle-shaped cells are prematurely destroyed, leading to a shortage of red blood cells and anemia.
• Organ damage: Chronic blockages can damage organs, including the spleen, liver, kidneys, and brain.
• Increased risk of infection: Sickle cell anemia patients have an increased risk of infections due to impaired immune function.
• Stroke: Sickle-shaped cells can block blood flow to the brain, causing a stroke.

Diagnosis of Sickle Cell Anemia

The diagnosis of sickle cell anemia involves a combination of laboratory tests and clinical findings. The definitive test for sickle cell anemia is hemoglobin electrophoresis, which separates the different types of hemoglobin in the blood.

Hemoglobin Electrophoresis

Hemoglobin electrophoresis is a laboratory test that separates the different types of hemoglobin in the blood. In sickle cell anemia, the abnormal hemoglobin S migrates differently from normal hemoglobin A during electrophoresis, allowing for its identification.

Other Laboratory Tests

• Complete blood count (CBC) : A CBC shows a decreased red blood cell count, increased white blood cell count, and decreased hemoglobin levels.
• Peripheral blood smear : A peripheral blood smear shows the characteristic sickle-shaped red blood cells.
• Reticulocyte count : A reticulocyte count measures the number of immature red blood cells in the blood, which is increased in sickle cell anemia due to increased red blood cell destruction.

Differential Diagnosis

The differential diagnosis of sickle cell anemia includes other conditions that can cause similar symptoms, such as:

• Thalassemia : A group of genetic disorders that affect the production of hemoglobin.
• Iron deficiency anemia : A condition caused by a lack of iron in the body.
• Vitamin B12 deficiency anemia : A condition caused by a lack of vitamin B12 in the body.

Treatment of Sickle Cell Anemia: Sickle Cell Anemia Case Study Hesi

Treatment for sickle cell anemia aims to alleviate symptoms, prevent complications, and improve overall quality of life. It involves a combination of medications, therapies, and lifestyle modifications.

Medications

• Hydroxyurea : This medication helps prevent the formation of sickle-shaped red blood cells, reducing the frequency and severity of sickle cell crises.
• Pain relievers : Over-the-counter pain relievers, such as ibuprofen or acetaminophen, can help manage pain during sickle cell crises.
• Antibiotics : Antibiotics are prescribed to prevent infections, which can be particularly dangerous for people with sickle cell anemia.
• Blood transfusions : Blood transfusions can replace damaged red blood cells and help prevent complications, such as stroke or organ damage.
• Hydroxyurea therapy : Hydroxyurea can also be administered as an intravenous infusion to treat severe sickle cell crises.
• Bone marrow transplant : A bone marrow transplant can cure sickle cell anemia by replacing the patient’s bone marrow with healthy bone marrow from a donor.

Lifestyle Modifications

• Hydration : Staying well-hydrated helps prevent dehydration, which can trigger sickle cell crises.
• Exercise : Regular exercise can improve circulation and reduce pain, but it’s important to avoid strenuous activity that may trigger a crisis.
• Avoiding triggers : Certain triggers, such as extreme heat or cold, can worsen sickle cell symptoms. Avoiding these triggers can help reduce the frequency and severity of crises.

Nursing Management of Sickle Cell Anemia

Nurses play a pivotal role in the comprehensive care of patients with sickle cell anemia. They provide essential support, education, and interventions to alleviate symptoms, prevent complications, and enhance the quality of life for these patients.

Role of the Nurse in Sickle Cell Anemia Care

Nurses are responsible for assessing, monitoring, and managing the various aspects of sickle cell anemia. They:

• Conduct comprehensive assessments to identify symptoms, assess pain severity, and monitor for complications.
• Administer medications as prescribed, including pain relievers, antibiotics, and hydroxyurea.
• Provide patient and family education on the disease, its management, and available resources.

Nursing Interventions for Managing Pain in Sickle Cell Anemia

Pain is a hallmark symptom of sickle cell anemia. Nurses play a crucial role in managing pain effectively through:

• Administering pain relievers as prescribed, including opioids and non-steroidal anti-inflammatory drugs (NSAIDs).
• Applying heat or cold therapy to affected areas.
• Providing relaxation techniques, such as guided imagery and deep breathing exercises.
• Encouraging distraction techniques, such as listening to music or reading.
• Monitoring pain levels regularly and adjusting interventions as needed.

Nursing Interventions for Preventing and Treating Infections in Sickle Cell Anemia

Patients with sickle cell anemia are at increased risk of infections due to impaired immune function. Nurses implement preventive and treatment measures to minimize the risk of infections, including:

• Administering prophylactic antibiotics, such as penicillin, to prevent infections in young children.
• Providing education on infection prevention, including hand hygiene, avoiding contact with sick individuals, and seeking prompt medical attention for any signs of infection.
• Monitoring for signs and symptoms of infection, such as fever, chills, and cough.
• Initiating early treatment with appropriate antibiotics if an infection occurs.
• Collaborating with physicians to manage any underlying conditions that may contribute to the risk of infection.

Case Study of Sickle Cell Anemia

Sickle cell anemia is an inherited blood disorder that affects the shape of red blood cells. Red blood cells are normally round and flexible, but in people with sickle cell anemia, they are sickle-shaped and rigid. This can cause the cells to get stuck in small blood vessels, blocking blood flow and causing pain, tissue damage, and other complications.

The following is a case study of a patient with sickle cell anemia.

Patient History

The patient is a 20-year-old African American male with a history of sickle cell anemia. He was diagnosed with the condition at birth and has been hospitalized multiple times for pain crises, infections, and other complications.

Physical Examination

On physical examination, the patient is in pain and has a fever. His heart rate is elevated, and his respiratory rate is increased. He has pallor, jaundice, and hepatosplenomegaly.

Laboratory Findings

The patient’s laboratory findings include:

• Hemoglobin: 6 g/dL
• Hematocrit: 18%
• White blood cell count: 15,000/μL
• Platelet count: 100,000/μL
• Reticulocyte count: 10%
• Sickle cell test: positive

Treatment Plan

The patient’s treatment plan includes:

• Pain medication
• Blood transfusions
• Hydroxyurea
• Antibiotics

The patient’s pain has improved, and his fever has subsided. He has been discharged from the hospital and is doing well at home.

The case study of sickle cell anemia highlights the challenges faced by individuals living with this debilitating condition and the critical role of nurses in their care.

Implications for Nursing Practice, Sickle cell anemia case study hesi

The case study emphasizes the need for nurses to:

• Understand the pathophysiology of sickle cell anemia and its implications for patient care.
• Assess and monitor patients for complications, such as pain crises, infections, and organ damage.
• Develop and implement individualized care plans that address the patient’s physical, emotional, and social needs.
• Provide education and support to patients and their families to empower them in managing the condition.
• Collaborate with other healthcare professionals to ensure comprehensive and coordinated care.

Helpful Answers

What is the most common symptom of sickle cell anemia?

Painful episodes, known as vaso-occlusive crises, are the most common symptom of sickle cell anemia.

How is sickle cell anemia diagnosed?

Sickle cell anemia is diagnosed through a blood test called hemoglobin electrophoresis, which identifies the presence of sickle-shaped red blood cells.

What is the goal of treatment for sickle cell anemia?

The goal of treatment for sickle cell anemia is to prevent and manage complications, relieve pain, and improve the quality of life for patients.

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• v.11(5); 2021

A case of Sβ+ sickle cell disease diagnosed in adulthood following acute stroke: it’s 2021, are we there yet?

a University of California Irvine Medical Center, Orange, CA, USA

b Division of Hematology Oncology, Department of Medicine, Orange California, CA, USA

Danielle Brazel

Zahra pakbaz.

In this report, we present a 29-year-old African American female who was brought to a local emergency department after being found unresponsive by her mother. The etiology of her stroke and severe hemolysis remained unknown, despite her mother reporting the patient’s history of co-inheritance of sickle cell trait and beta-thalassemia trait, and extensive workup during her prolonged hospitalization. She was diagnosed with sickle cell disease (Sβ+ type) two years after discharge when she was referred to a sickle cell specialist for persistent anemia. Here, we also briefly review the challenges to diagnose rarer subtypes of sickle cell disease (SCD), in this case Sβ+ type, as well as the pathophysiology and current management of stroke in SCD.

1. Introduction

Sickle cell disease (SCD) is an inherited hemoglobinopathy with devastating, multi-system complications when sub-optimally managed. According to the latest estimates from the Centers for Disease Control and Prevention, approximately 100,000 people in the USA live with SCD [ 1 ]. Over the past several decades, survival has improved in children with SCD by implementation of widespread newborn screening, penicillin prophylaxis, pneumococcal vaccination for encapsulated bacteria, and hydroxyurea. However, the overall life expectancy in individuals with SCD in the USA is estimated to be 43 years due to high morbidity and mortality in adulthood [ 2 ]. Cerebrovascular disease is a particularly concerning complication of SCD, as both silent cerebral infarcts and overt stroke lead to cognitive and functional deficits over time [ 3 ].

In this report, we present the case of an African American woman with SCD (Sβ+ type), whose SCD was not diagnosed until two years after she developed acute stroke at age 29 years, requiring admission to the ICU. We briefly review here the challenges to diagnose compound heterozygous types of SCD, in this case Sβ+ type, as well as the pathophysiology and current management of stroke in SCD.

2.1. Initial presentation and hospital course

A 29-year-old African American female was brought to a local emergency department (ED) by her mother after being found unresponsive at home in decorticate posture, profusely diaphoretic with urinary incontinence. While in the ED, she developed hypotension, hypothermia, and respiratory failure with an oxygen saturation of 80% and agonal respirations. She was subsequently intubated and admitted to the ICU for management of possible seizure and sepsis. The patient’s mother reported that she had experienced flu-like symptoms for two weeks prior to presentation, for which she had been taking over-the-counter cold medications. Earlier on the day of admission, she had demonstrated acute confusion and later became unresponsive. During history taking, her mother also mentioned that the patient had ‘sickle cell trait and beta-thalassemia trait.’

Initial laboratory workup in the ED revealed Coombs negative severe hemolytic anemia with hemoglobin 6.8 g/dL, absolute reticulocytes 0.05 tril/L, reticulocyte production index 0.79%, hematocrit 19.2%, MCV 76.5 fL, and severe thrombocytopenia with platelets 24 bil/L, for which she received packed red blood cells (PRBC) and platelet transfusions. Peripheral blood smear showed few spherocytes, few target cells, and few tear cells without schistocytes. Additional laboratory analysis revealed LDH and lactate elevated to 4385 U/L and 6.0 mMol/L, respectively, total bilirubin 1.7 mg/dL, AST 236 U/L, ALT 80 U/L, and D-dimer >21.0 mcg/mL with elevated fibrinogen. Urine drug screen was positive for amphetamines (later she denied using amphetamine but reported that she might have had passive exposure) and marijuana, which she was consuming for chronic pain of unknown etiology.

Additional studies obtained on hospital day 1 included CT and MRI of the brain which were read as unremarkable, EEG showing diffuse slowing of brain waves without evidence of seizure, and CT scan of the chest demonstrating mild chronic interstitial lung changes bilaterally and multiple lung nodules without evidence of pulmonary embolism. CT scan of the abdomen performed on day 2 revealed high-intensity material within the gallbladder, mild hepatosplenomegaly, and ‘fishmouth’ deformities of the lumbar spine vertebrae. Subsequent gallbladder ultrasound demonstrated biliary sludge without evidence of discrete stones. Follow-up CT chest showed left lower lung consolidation on day 4.

Given the evidence of severe hemolysis, thrombocytopenia, and altered mental status, hematology recommended emergent empiric plasma exchange due to concern for thrombotic thrombocytopenic purpura (TTP). Empiric broad-spectrum antibiotics, fluconazole, and acyclovir were discontinued on day 5 after a negative infection workup including a negative lumbar puncture. Despite 4 days of plasma exchange treatments, there was no improvement in her clinical or laboratory status. She was therefore transferred to a tertiary care center on day 7 for higher level of care.

2.2. Tertiary care hospital course

Upon transfer, hematology discontinued plasma exchange given a normal ADAMTS13 (resulted on day 7), which ruled out TTP. Hemoglobin electrophoresis performed on day 8 was interpreted as sickle cell trait and beta-thalassemia trait (Hgb A 74.1, Hgb F 0.0, Hgb S 22.1, Hgb A2 of 3.8, Hgb C 0.0). Haptoglobin dropped to <10 mg/dL. On day 15, total bilirubin peaked at 3.7 mg/dL, with AST and ALT reaching maximums of 634 U/L and 559 U/L, respectively, and thrombocytopenia recovered. Further laboratory investigation failed to establish the etiology of the patient’s loss of consciousness and ongoing hemolysis. Folate was normal, while vitamin B12 was low at 342.2 pg/mL. Her autoimmune panel was negative, and she did not meet the Sydney Criteria for antiphospholipid syndrome. Peripheral blood flow cytometry for paroxysmal nocturnal hemoglobinuria and G6PD deficiency testing were both normal. Serology for HCV, HBV, HIV and Parvo virus was negative. TSH was also within the reference range.

A second MRI brain obtained on day 7 revealed multiple scattered microthrombi, bilateral chronic subdural hematomas, diffusion restriction in the splenium of the corpus callosum, and extramedullary hematopoiesis in the calvarium ( Figure 1 ). Her initial MRI from the day of admission was reread by a neuroradiologist, who noted multiple lesions suggestive of a ‘shower of emboli.’ Echocardiogram did not show any intracardiac thrombi or septal defect and electrocardiogram confirmed sinus tachycardia. Abdominal ultrasound with duplex on day 11 revealed mild hepatomegaly (17.5 cm) with splenomegaly (13.5 cm), increased heterogeneous echogenicity of the spleen, along with mildly elevated main hepatic artery peak systolic velocity. Bone marrow biopsy obtained on day 16 demonstrated hypo-cellular marrow with extensive degenerative changes and markedly decreased trilineage hematopoietic cells, consistent with bone marrow necrosis. The patient required a total of 4 more units of PRBC during her hospitalization to maintain hemoglobin above 8 g/dL.

A. Axial  diffusion weighted  image (DWI): Multiple foci of restricted diffusion including a dominant peri-centimeter region in the right splenium of the corpus callosum(see arrow);  B.  Axial T2/FLAIR at the level of the centrum semiovale:  Hyperintense foci indicative of vasogenic edema in the bilateral white matter including deep and subcortical aspects (encircled in white). Incidental bilateral cerebral convexity subdural collection that are hyperintense in signal (and intermediate intensity on T1) favoring chronic subdural hematomas (encircled in red);  C.  Axial susceptibility weighted image (SWI) at the level of the cerebellum: Numerous hypointense foci indicative of microhemorrhages throughout the cerebellum and brain stem

2.3. Hospital discharge and outpatient follow-up

Supportive care was continued and the patient’s mental status gradually improved. She was subsequently extubated on day 21 of her hospital stay and discharged to an acute rehabilitation facility on day 52. Upon discharge, she was neurologically alert and responsive with globalized weakness and expressive aphasia. Approximately two years later, the patient was referred to a sickle cell clinic for persistent anemia. On further detailed questioning, she reported pain while swimming and unexplained occasional pain episodes during childhood with progressive severity for which she eventually started using marijuana. Hemoglobin electrophoresis was obtained and suggested SCD (Hgb A 20.5%, Hgb F 3.9%, Hgb A2 7.7%, Hgb S 67.9%). Further DNA testing revealed heterozygous positivity for hemoglobin S (c.20A>T) and a thalassemia trait/β+ mutation/pathogenic variant (c.-79A>G) in the promoter of the beta globin gene – 29 base pairs upstream of the transcription start site. DNA testing also demonstrated four alpha globin genes with duplication of the mid-portion of the alpha-2 globin gene. This confirmed the diagnosis of SCD, Sβ+ type. In subsequent visits, additional workup showed avascular necrosis of the bilateral hips and left shoulder (indicative of stage III or early stage IV FICAT avascular necrosis, Figures 2 &3 ). Abdominal ultrasound confirmed resolution of hepatosplenomegaly. Per patient preference, chronic transfusions were not started, and hydroxyurea was initiated instead. She demonstrated a strong response to hydroxyurea with Hb F > 20% but developed pancytopenia at a dose of 30 mg/kg, requiring a decrease in dosage leading to decline in HbF. Therefore, she chose to add voxelotor given residual pain and low HbF and total hemoglobin interfering with her quality of life. At the time of this publication (4 years after initial stroke), she has not developed recurrent stroke and continuous physical therapy has improved her gait, musculoskeletal strength, and speech.

Coronal PD MRI of left and right hips without contrast showing serpentine low signal irregularity along the weightbearing portion of the femoral head with associated rim of edema compatible with avascular necrosis. There are extensive regions of bonny infarctions involving the entire visualized bony pelvis (including the pubic body, ischial tuberosity, iliac wing and sacrum) and proximal femur/intertrochanteric region. Both studies are indicatvie of stage 3 and suspected early stage 4 FICAT femoral head avascular necrosis

. MRI left shoulder demonstrating serpiginous PD hyperintense and T1 hypointense signal along the peripheral margin of the humeral head. These fingidngs are consistent with avascular necrosis of the left humeral head

3. Discussion

This case presents a 29-year-old female with lifelong unrecognized sickle cell disease, Sβ+ type. She presented to the emergency room with severe hemolytic anemia, acute stroke, acute respiratory failure, and alveolar hemorrhage due to thrombocytopenia secondary to hepatosplenic sequestration. This clinical presentation, along with the patient’s reported personal history of sickle cell trait and thalassemia trait, pain while swimming, unexplained progressive pain, and family history of beta-thalassemia trait (mother) and sickle cell trait (father), suggests sickle cell disease (SCD). Additionally, the typical bone marrow biopsy findings, multiple-imaging reports noting osseous sequelae of SCD (e.g., ‘fishmouth’ deformities), and chronic interstitial lung changes on CT chest further suggest a chronic sickling process.

SCD is an autosomal recessive hemolytic anemia following Mendelian inheritance. Its complex pathophysiology is due to the presence of excess hemoglobin S (HbS), which results from the substitution of the hydrophilic glutamic acid with hydrophobic valine in position 6 of the beta globin gene. HbS polymerizes under low oxygen tension, leading to repeated cycles of sickling that result in vaso-occlusive pain crisis and hemolysis with RBC lifespan 1/6 th that of normal RBCs [ 4 , 5 ]. The co-inheritance of HbS with other beta globin gene mutation variants results in several SCD subtypes. The most common genotypes are sickle cell SS (also known as sickle cell anemia) and Sβ 0 . These subtypes frequently present with vaso-occlusive crises, hemolytic crises, or both. By contrast, Sβ+ and SC are rarer genotypes and usually initially present with less severe anemia and infrequent vaso-occlusive crises in childhood. Over time, patients with these subtypes often gradually develop multiple complications such as stroke, avascular necrosis of bones requiring joint replacement, sickle cell retinopathy, and hepatosplenic sequestration [ 6–8 ]. Due to their gradual clinical progression, these rarer subtypes may be misunderstood and remain undiagnosed for years, such as in this case. A potential means of reducing the confusion may be to update the terminologies currently used by experts to name these compound heterozygous sickle cell variants. For example, using ‘Sβ+ sickle cell disease’ or ‘Sickle cell disease, Sβ+ type’ instead of ‘sickle cell trait beta-thalassemia trait’ may help patients and clinicians better understand the significance of this diagnosis. In the present case, both the patient’s family and her providers knew she had co-inherited sickle and beta-thalassemia mutations but were unaware that this coinheritance is one of the several subtypes of sickle cell disease.

The result of patients’ post-transfusion hemoglobin electrophoresis often is misinterpreted as sickle cell trait and thalassemia trait. In our patient’s test, the low hemoglobin S was due to dilution of the patient’s hemoglobin S by transfused RBCs received during her hospitalization. Her high HbA also reflected transfused RBCs rather than the patient’s own RBCs. Co-inheritance of the sickle cell mutation with another hemoglobin variant – if in the trans position – results in sickle cell disease and there is no other interpretation. The trans position can be confirmed with family testing showing that one parent has one sickle cell mutation, and the other parent carries another pathologic beta globin mutation variant. Additionally, falsely elevated HbA2 in SCD may lead to the incorrect conclusion that the patient has beta thalassemia trait [ 9 ]. The most accurate way to confirm SCD type is genetic testing, which also provides the information necessary to offer comprehensive genetic counseling. Hypochromic microcytosis in individuals with SCD in the absence of iron deficiency may reflect additional alpha or beta globin gene abnormalities. This was true for the patient in the present case, who had an MCV of 73.7 fL and MCH of 24.1 pg in the absence of iron deficiency. She also had a partial alpha duplication in addition to a beta trait mutation, which could contribute to the increased severity of her SCD.

Ischemic stroke is a well-established complication of SCD, with a recent study suggesting an incidence rate of approximately 2% in children and young adults [ 10 ]. While the existing literature suggests that the overall risk of stroke is lower among Sβ+ patients, it still represents a significant source of morbidity [ 6–8 ]. This is evident in the patient described in this report, who continues to have gait problems and imbalance, expressive aphasia, and cognitive impairment requiring her mother to oversee her overall care. The increased stroke risk in SCD is attributed to several mechanisms. First, repeated sickling episodes are thought to cause pathologic adherence of abnormal erythrocytes to the vascular endothelium, contributing to vascular injury, intimal hyperplasia, NO dysregulation, and intraluminal thrombosis [ 5 , 11 , 12 ]. These processes lead to the progressive stenosis of the cerebral arteries and the development of collateral vessels resembling moyamoya angiopathy [ 13 , 14 ]. Second, abnormal oxygen delivery and chronic anemia in SCD lead to decreased arterial oxygen content (CaO 2 ), which also contributes to stroke development [ 15 ]. Therefore, during acute severe hemolytic anemia or acute chest syndrome, cerebrovascular dilatory reserve reaches maximal capacity and cerebral blood flow cannot compensate for the acute decrease in CaO 2 , resulting in ischemia [ 16 ]. Chronic anemia and elevated cerebral blood flow may further predispose to cerebral vasculopathy due to chronic shear stress [ 15 ]. Third, ‘cerebral fat embolism syndrome’ in the absence of PFO, described more commonly in case reports and case series of compound heterozygous types, might be the main cause of stroke in this case [ 17 ]. Last but not least, SCD is also characterized as a hypercoagulable state, which may further elevate stroke risk [ 18 ].

It is well known that the cornerstone of primary and secondary stroke prevention in children with SCD is the use of transcranial Doppler (TCD) to identify children at risk of stroke and initiate prophylactic blood transfusions [ 19 , 20 ]. However, at this time there are no evidence-based, effective stroke prevention and management recommendations specific to adults with SCD, despite increased risk of stroke incidence by age [ 21 ]. Instead, it is recommended that adults with SCD receive evaluation and treatment for traditional stroke risk factors as in the general population, such as hypertension, hyperlipidemia, and atrial fibrillation. In adults with acute stroke and SCD, prompt blood transfusion is recommended, with exchange transfusion preferred to simple transfusion when possible and appropriate. According to the American Society of Hematology (ASH) 2020 guidelines, evaluation for revascularization surgery and regular blood transfusions are conditionally suggested as secondary prevention for adults with SCD and evidence of moyamoya syndrome, though very limited evidence for these recommendations exist and recommendations are extrapolated from pediatric sickle cell data [ 22 ]. Although hydroxyurea is the recommended treatment for reducing vaso-occlusive events in SCD, the data supporting its utility instead of blood transfusions for stroke prevention in children continues to evolve [ 22–24 ]. The use of hydroxyurea for stroke prevention in adults with SCD remains to be studied.

4. Conclusion

This report presents the case of a young adult with Sβ+ sickle cell disease whose condition was not diagnosed until after she developed an acute stroke at age 29 years requiring ICU admission. This delay occurred despite the fact she had undergone genetic testing early in her life and that she and her providers had known for years that she co-inherited the hemoglobin S and beta thalassemia (β+) mutations. Perhaps this could have been prevented by using the term ‘Sβ+ sickle cell disease’ for her diagnosis instead of ‘sickle cell trait beta thalassemia trait’. This case underscores the need to establish effective educational programs to raise clinicians’ awareness of the diagnosis and management of SCD and its subtypes, evidenced by the fact that all studies conducted during this patient’s hospitalization provided clues towards a diagnosis of SCD. It also illustrates the fact that acute stroke and other complications of sickle cell anemia can occur in adults with compound heterozygous SCD (Sβ+ type in this case) if not managed properly. While these subtypes are often considered to be milder forms of the disease, this is a potentially misleading characterization. Last but not least, further research is warranted to identify effective primary and secondary stroke prevention measures for adults with SCD.

Acknowledgments

The patient provided consent to publish the information contained in the manuscript above.

The authors would like to thank the patient and her mother for helping reconstruct this case accurately to the best of their knowledge after review of her outside records.

The authors would also like to thank neuroradiologist Edward Kuoy, MD for his assistance in re-reading and preparing the Brain MRI figure for publication.

Disclosure statement

At the time of this submission, author ZP is GBT speaker bureau, received consultancy honorarium from GBT, ZP is speaker bureau and medical advisor for TerumoBCT.