Elliptocytes, causes, prognosis & Treatment.pptx

Elliptocytes

1. Hereditary Elliptocytosis

2. INFORMATION:- Hereditary elliptocytosis encompasses a range of inherited red blood cell (RBC) membrane disorders manifested by elliptical-shaped RBCs. The condition is diverse, ranging from asymptomatic cases to severe hemolysis. 3) Effective management is related to tailoring interventions dependent on the severity of symptoms, with options including no treatment for asymptomatic individuals and splenectomy for severe cases.  Clinicians participating in this activity on hereditary elliptocytosis can expect to get a comprehensive understanding of the condition. The information gives an idea about the diverse spectrum of hereditary elliptocytosis , from asymptomatic cases to severe hemolysis, providing insights into the nuances of its presentation.  6)Afterwards , participants will glean insights into the collaborative approach involving an interprofessional team in evaluating a s well as treating hereditary elliptocytosis , emphasizing the importance of a holistic perspective in patient care. 7)Finally , this activity equips clinicians with the knowledge and skills required to manage and navigate the complexities of hereditary elliptocytosis in an effective manner.

3. OBJECTIVES:- Identify the varying presentations of hereditary elliptocytosis, differentiating between asymptomatic cases and those requiring intervention. 2) Select appropriate diagnostic tools and genetic testing methods for identifying and classifying hereditary elliptocytosi s in an accurate manner. 3) Implement tailored interventions dependent on the severity of hereditary elliptocytosis symptoms, ranging from no treatment for asymptomatic cases to splenectomy particularly for severe hemolysis. 4) Communicate with patients in an effective manner , ensuring they comprehend the impact of hereditary elliptocytosis on their quality of life and empowering them in their healthcare aspects

4. I NTRODUCTION:_ Hereditary elliptocytosis, or hereditary ovalocytosis, is an inherited heterogeneous red blood cell (RBC) disorder manifested by elongated, oval, or elliptical-shaped RBCs on the peripheral blood smear.

5. Genetic alterations in α-spectrin, β-spectrin, protein 4.1, band 3, and, rarely, glycophorin C lead to the loss of the normal elastic recoil property in RBCs within the peripheral circulation, resulting in their distinctive elliptical shape. 3) The spleen plays a n important role in the manifestation of the disorder, as it captures and removes these abnormal elliptocytes, finally causing hemolytic anemia. 4) Elliptocytosis was first described by Dresbach in 1904, and its hereditary nature was firmly established by Hunter. 5) Hereditary elliptocytosis en closes various subtypes, each with distinct characteristics. 6)An example for t hese subtypes are common hereditary elliptocytosis, hereditary pyropoikilocytosis (HPP), Southeast Asian ovalocytosis (SAO), and spherocytic elliptocytosis (SE). 7) The differentiation among these subtypes lies in variations in RBC morphology and the degree of hemolysis. 8) The majority of individuals with hereditary elliptocytosis are asymptomatic and, therefore, do not necessitate any specific treatment. 9)Whatever it may be , for symptomatic patients, effective management may require interventions namely blood transfusions and splenectomy. 10) These approaches aim to address and alleviate the symptoms rrgarding the condition.

6. ETIOLOGY:_ The elastic deformability of RBCs is  particularly influenced by the cytoskeleton proteins located beneath the cell membrane. The 5 interconnected proteins  essential to this process are spectrin, ankyrin, protein 4.2, band 3 protein, and glycophorin C. Any genetic abnormalities influencing these proteins can  change their structure and function, leading to abnormal RBCs and compromised deformability. Most hereditary elliptocytosis cases are because of genetic defects impacting α-spectrin, β-spectrin, protein 4.1, band 3, and rarely glycophorin C.  These genetic alterations include single base substitution, insertions, deletions, or modifications in mRNA processing.

7. The genes associated with these mutations include SPTA1 for α-spectrin, SPTB for β-spectrin, and EPB41 for protein 4.1. Among these, SPTA1 mutation is the most prevalent in hereditary elliptocytosis, happening in 65% of cases, followed by mutations in SPTB (30%) and EPB41 (5%). 8) Hereditary elliptocytosis follows an autosomal dominant inheritance pattern in a typical manner, except HPP, which is inherited in an autosomal recessive manner. An α-spectrin mutation manifests HPP juxtaposed in a transformation noted as α-LELY.

8. PATHOPHYSIOLOGY:- The normal RBC membrane co nsists of  a lipid bilayer and cytoskeleton proteins cr itical for regulating membrane integrity and surface area. These cytoskeleton proteins include spectrin (composed of α and β heterodimers), ankyrin, protein 4.1, protein 4.2, band 3, and glycophorin C. Genetic alterations influencing α-spectrin, β-spectrin, protein 4.1, band 3, and rarely glycophorin C lead to defects in RBC membrane stability and deformability particularly  during their passage through the microcirculation. Consequently, RBCs struggle to regain their normal biconcave shape  because of the loss of elastic recoil, leading to a fixed morphology of elliptocytes in peripheral blood. These elliptocytes become entrapped and  removed by the spleen, leading to in the premature destruction of the RBCs (<120 days) and prominent intravascular hemolysis, a pr ominent feature in hereditary elliptocytosis. 

9. The severity of anemia directly correlates with the degree of reduction regardiung RBC membrane stability. 7) Individuals heterozygous for an elliptocytic variant typically remain asymptomatic. 8) In contrast, those who are homozygous or compound heterozygous for hereditary elliptocytosis variants may ex hibit mild-to-severe anemia. 9) The membranes in HPP are reportedly uniquely susceptible to thermal stressors, demonstrating unique instability. 10) In HPP, the α-spectrin cannot associate in dimeric form with the β-spectrin, dis turbing the membrane cytoskeleton. 11) This disturbance results in a membrane elasticity loss, making it prone to hemolysis.  12) HPP is typically biallelic, unlike the monoallelic inheritance pattern seen in hereditary elliptocytosis. Individuals with HPP carry either a homozygous or compound heterozygous mutation, c ausing phenotypic heterogenicity. 13) The clinical polymorphism observed in HPP influences the genetic variations underlying the condition.

10. HISTORY AND PHYSICAL:- Most cases of hereditary elliptocytosis are asymptomatic and may be discovered in an incident manner particularly during the investigation of anemia. Whatever it may be , some individuals may exhibit symptoms namely fatigue or reduced exercise tolerance because of anemia. It is essential to emphasize on anemia within family members, as hereditary elliptocytosis may be misdiagnosed as another condition like iron deficiency anemia. 4)Hereditary elliptocytosis may present as neonatal jaundice in a rare manner. 5) Long- standing hemolytic anemia associated with hereditary elliptocytosis can lead to  splenomegaly, manifested by early satiety, left upper quadrant abdominal pain, and abdominal discomfort.

11. 6) Patients with HPP may display frontal bossing, while chronic hemolysis can result in leg ulcers. 7) The presentation varies among the different subtypes of hereditary elliptocytosis, each of which is explained below. 8) Common hereditary elliptocytosis explains about the most prevalent form of hereditary elliptocytosis, and patients are typically asymptomatic. 9) Neonates with this condition may  lead to  transient hemolysis, which typically resolves within the first year of life. 10) In cases of severe hemolytic anemia and jaundice in neonates, transfusion and phototherapy may be  required . The defining characteristic of common hereditary elliptocytosis is the presence of elliptical-shaped RBCs particularly in the peripheral blood smear, constituting anywhere from 15% to 100% of the total RBCs. 11) The peripheral blood smear may also demonstrate spherocytes, stomatocytes, and poikilocytes (fragmented cells). 12) HPP stands out as the most severe form of hereditary elliptocytosis, essentially infl;uencing African-American neonates. These infants typically exhibit with neonatal jaundice and persistent hemolytic anemia throughout their lives.

12. 13) The peripheral blood smear in HPP  indicates  poikilocytes and spherocytes with rare elliptocytes. 14) Microspherocytes are observed , with a mean corpuscular volume (MCV) of 30 to 50 gL. 15) In some cases, the cellular morphology may resemble those of thermal burn patients, displaying microspherocytes and erythrocyte fragments.  16) Neonates influenced by HPP often experience complications re garding hemolysis, like splenomegaly and the formation of pigment gallstones, necessitating interventions like transfusion and splenectomy. 17)Besides , the profound hemolysis in neonates with HPP may challenges namely an enhanced risk of severe anemia, emphasizing the importance of prompt and targeted medical interventions. 18) SAO, also  termed as stomatocytosis elliptocytosis, is predominantly  seen in regions endemic to malaria. 19) This condition is manifested by mild or no hemolysis and  arranges resistance against  Plasmodium falciparum  infection. 20) The peripheral blood smear of individuals with SAO  shows stomatocytes, ovalocytes, and macro-ovalocytes.

13. 21) The underlying cause of this entity is a deletion within the SLC441 gene that encodes erythrocyte band 3. 22) SE is observed in a frequent manner particularly in individuals of Italian descent and is related to mild to moderate hemolysis. 23) Di fferentiating between HS and hereditary elliptocytosis using ektacytometry can be effective, but challenges may arise in the presence of HPP. 24) The intricate pattern of ektacytometry and morphological features of HPP may give rise to difficulties for differentiation. 25) In such cases, genetic analysis can  arrange  valuable assistance . 26) Physical examination findings in hereditary elliptocytosis include pallor in individuals undergoing hemolysis and observable signs namely splenomegaly. 27) Besides , right upper quadrant pain may be observed in patients with gallstones re garding hemolysis.

14. DIAGNOSIS:_ The evaluation of hereditary elliptocytosis is initiated with a comprehensive assessment, along with a complete blood count (CBC) demonstrating normocytic normochromic anemia. A peripheral blood smear is essential,  demonstrating elliptocytes in 15% to 100% of RBCs in a typical manner, along with other variations, namely spherocytes, stomatocytes, poikilocytes, ovalocytes, and macro-ovalocytes. Testing for hemolysis reveals features of extravascular hemolysis manifested by an e nhanced reticulocyte count, enhanced lactate dehydrogenase, indirect bilirubin, and reduced haptoglobin level. The predominance of elliptocytes does not consistently correlate with the severity of hemolysis. Polychromasia is expected with hemolysis a s well as reticulocytosis. 

15. For a more detailed analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) can quantify protein 4.1 and spectrin. Besides , morphologic and genetic studies are analyzed by ektacytometry, which reveals characteristic responses of the erythrocyte membrane to laser diffraction a s well as biomechanical stressors. 7) In cases where splenomegaly is suspected, ultrasonography is the  required and cost-effective diagnostic tool. Computed tomography (CT) and magnetic resonance imaging (MRI) may also be needed for further investigation. 

16. Treatment / Management Asymptomatic individuals without hemolysis do not need treatment or regular follow-up. The priority is to educate the patient regarding the nature of the disease and ensure proper documentation in the patient's records to stop unnecessary testing.  Individuals experiencing intermittent hemolysis or anemia may necessitate blood transfusions if symptomatic or if their hemoglobin level  decreases below the age-specific threshold. Splenectomy is considered for patients facing severe, life-threatening anemia or requiring regular blood transfusions.  Whatever it may be , vaccination against pneumococcus, meningococcus, and Haemophilus influenza is mandatory particularly  before surgery because of the associated heightened risk of infection along with with encapsulated organisms.

17. Differential Diagnosis The differential diagnosis of hereditary elliptocytosis includes various conditions: Hereditary spherocytosis 2) Glucose-6-phosphate dehydrogenase (G6PD) deficiency 3) Thalassemia: Coinheritanced with hereditary elliptocytosis may present as a non-transfusion-dependent patient with marked poikilocytosis and fragmented cells. 4) Pyruvate kinase deficiency 5) Hereditary

18. 5) Hereditary stomatocytosis/xerocytosis 6) Iron deficiency anemia 7) Megaloblastic anemia 8) Sickle cell anemia 9) Myelofibrosis 10) Myelodysplastic syndrome, although rare, acquired elliptocytosis can be seen  in a myelodysplastic setting. The most common genetic defect of HE/MDS is del20q. 

19. PROGNOSIS:- Most patients with hereditary elliptocytosis are asymptomatic, and only a small percentage (5%-20%) demonstrate uncompensated hemolysis  resulting in anemia. 2) Even among those with severe hemolysis who undergo treatment with splenectomy, the prognosis is usually favorable, pointing out the overall benign course of the condition.

20. Complications Complications associated with hereditary elliptocytosis include: Megaloblastic anemia may result from folate and Vitamin B12 deficiency  because of chronic hemolysis. The deficiency may happen due to nutritional factors, functional issues re garding significant erythrocyte production, or a combination Supplementation with vitamin B12 or folate can help alleviate this issue.    Pigment gallstones: May result in complications namely cholangitis, cholecystitis, and pancreatitis.   Splenomegaly: Patients may experience functional and moderate splenomegaly justlike many hemolytic anemias.

21. Renal tubular acidosis: Associated with SAO, wherein familial distal renal tubular acidosis is related to  this specific subtype.   Leg ulcers: Typically form around the medial malleoli, which are thought to happen particularly in hemolytic anemias because of stasis. Growth retardation and skeletal abnormalities: May develop due to marrow expansion.  

22. Consultations  While consultations with a specialist may not always be necessary, referrals to specific consultants may be needed particularly in certain c onditions and can include:  General surgeon: Especially for patients contemplating splenectomy. Genetic counselor: To provide comprehensive explanations regarding genetic transmission of the disease. Hematologist: This referral may be beneficial for perioperative assessment, administration of Vitamin B12 or folate, and engagement in transfusional therapy if needed.  

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