Hereditary spherocytosis: Difference between revisions
Jump to navigation
Jump to search
Amar Morani (talk | contribs) No edit summary |
Amar Morani (talk | contribs) No edit summary |
||
| Line 15: | Line 15: | ||
'''Hereditary spherocytosis''' is a genetically-transmitted form of [[spherocytosis]], an auto-[[Hemolysis|hemolytic]] [[anemia]] characterized by the production of red blood cells that are sphere-shaped rather than donut-shaped, and therefore more prone to [[hemolysis]]. | '''Hereditary spherocytosis''' is a genetically-transmitted form of [[spherocytosis]], an auto-[[Hemolysis|hemolytic]] [[anemia]] characterized by the production of red blood cells that are sphere-shaped rather than donut-shaped, and therefore more prone to [[hemolysis]]. | ||
== Historical Perspective | == Historical Perspective == | ||
* Towards the end of the nineteenth century Vanlair and Masius described the case of a young woman who developed icterus, recurrent attacks of left upper quadrant abdominal pain and [[splenomegaly]] shortly after giving birth. The [[stools]] were not light coloured, but rather deeply pigmented. The patient's mother and sister were also [[Icterus|icteric]], and the sister's [[spleen]]<nowiki/>was enlarged. | * Towards the end of the nineteenth century Vanlair and Masius described the case of a young woman who developed icterus, recurrent attacks of left upper quadrant abdominal pain and [[splenomegaly]] shortly after giving birth. The [[stools]] were not light coloured, but rather deeply pigmented. The patient's mother and sister were also [[Icterus|icteric]], and the sister's [[spleen]]<nowiki/>was enlarged. | ||
== Classification | == Classification == | ||
* Hereditary Spherocytosis classified on basis of underlying defect in protein and also on the basis of severity of hemolysis. | * Hereditary Spherocytosis classified on basis of underlying defect in protein and also on the basis of severity of hemolysis. | ||
== Pathophysiology | == Pathophysiology == | ||
There is intrinsic defects in erythrocyte membrane proteins that result in [[Red blood cell|RBC]] [[cytoskeleton]] instability. Loss of erythrocyte surface area leads to the spherical shape of RBCs (spherocytes), which are culled rapidly from the circulation by the [[spleen]]. [[Hemolysis]] mainly confined to the spleen and, therefore, is extravascular. Splenomegaly commonly develops. | There is intrinsic defects in erythrocyte membrane proteins that result in [[Red blood cell|RBC]] [[cytoskeleton]] instability. Loss of erythrocyte surface area leads to the spherical shape of RBCs (spherocytes), which are culled rapidly from the circulation by the [[spleen]]. [[Hemolysis]] mainly confined to the spleen and, therefore, is extravascular. Splenomegaly commonly develops. | ||
| Line 30: | Line 30: | ||
* [[Protein 4.2]] defects | * [[Protein 4.2]] defects | ||
== Causes | == Causes == | ||
* [[Hereditary spherocytosis|HS]] is caused by a variety of [[mutations]] that lead to defects in [[Red blood cells|red blood cell (RBC)]] membrane proteins. HS usually is transmitted as an [[autosomal dominant]] trait, and the identification of the disorder in multiple [[Generation|generations]] of affected families is the rule. [[Homozygosity]] for this dominantly transmitted [[Hereditary spherocytosis|HS]] [[gene]] has not been identified, which suggests that the [[homozygous]] state is incompatible with life. | * [[Hereditary spherocytosis|HS]] is caused by a variety of [[mutations]] that lead to defects in [[Red blood cells|red blood cell (RBC)]] membrane proteins. HS usually is transmitted as an [[autosomal dominant]] trait, and the identification of the disorder in multiple [[Generation|generations]] of affected families is the rule. [[Homozygosity]] for this dominantly transmitted [[Hereditary spherocytosis|HS]] [[gene]] has not been identified, which suggests that the [[homozygous]] state is incompatible with life. | ||
== Differentiating Hereditary spherocytosis overview from Other Diseases | == Differentiating Hereditary spherocytosis overview from Other Diseases == | ||
== Epidemiology and Demographics | == Epidemiology and Demographics == | ||
* HS is seen in all populations but appears to be especially common in people of northern European ancestry. | * HS is seen in all populations but appears to be especially common in people of northern European ancestry. | ||
| Line 41: | Line 41: | ||
** In northern European, HS affects as many as 1 in 2000 to 1 in 5000 (prevalence, approximately 0.02 to 0.05 percent). | ** In northern European, HS affects as many as 1 in 2000 to 1 in 5000 (prevalence, approximately 0.02 to 0.05 percent). | ||
== Risk Factors | == Risk Factors == | ||
* The risk factors for this condition have not yet been properly identified. | * The risk factors for this condition have not yet been properly identified. | ||
* However, having a family member with this condition can increase your susceptibility to this disease. The condition is also most common in individuals of North European origin although it has been found to arise in people of all races. | * However, having a family member with this condition can increase your susceptibility to this disease. The condition is also most common in individuals of North European origin although it has been found to arise in people of all races. | ||
== Screening | == Screening == | ||
* It is also important to test newborns of affected parents for HS, as affected newborns may have severe hyperbilirubinemia and anemia. This may be done by a clinician with expertise in hemolytic anemias or by a genetic counselor. It is possible for an individual with no hemolysis, no spherocytes on the blood smear, and a normal reticulocyte count to be a carrier of HS, which may be relevant in certain families. | * It is also important to test newborns of affected parents for HS, as affected newborns may have severe hyperbilirubinemia and anemia. This may be done by a clinician with expertise in hemolytic anemias or by a genetic counselor. It is possible for an individual with no hemolysis, no spherocytes on the blood smear, and a normal reticulocyte count to be a carrier of HS, which may be relevant in certain families. | ||
== Natural History, Complications, and Prognosis | == Natural History, Complications, and Prognosis == | ||
=== Natural History | === Natural History === | ||
* '''Disease severity and age of presentation''' — [[Hereditary spherocytosis|HS]] can present at any age and with any severity, with case reports describing a range of presentations, from [[hydrops fetalis]] in utero through diagnosis in the ninth decade of life. | * '''Disease severity and age of presentation''' — [[Hereditary spherocytosis|HS]] can present at any age and with any severity, with case reports describing a range of presentations, from [[hydrops fetalis]] in utero through diagnosis in the ninth decade of life. | ||
* The majority of affected individuals have mild or moderate hemolysis or [[hemolytic anemia]] and a known family history, making diagnosis and treatment relatively straightforward. Individuals with significant severe hemolysis may develop additional complications such as [[jaundice]]/[[hyperbilirubinemia]], [[folate deficiency]], or [[splenomegaly]]. | * The majority of affected individuals have mild or moderate hemolysis or [[hemolytic anemia]] and a known family history, making diagnosis and treatment relatively straightforward. Individuals with significant severe hemolysis may develop additional complications such as [[jaundice]]/[[hyperbilirubinemia]], [[folate deficiency]], or [[splenomegaly]]. | ||
=== Complications | === Complications === | ||
Common complications of [[hemolysis]] include [[neonatal jaundice]], [[splenomegaly]], and pigment gallstones. | Common complications of [[hemolysis]] include [[neonatal jaundice]], [[splenomegaly]], and pigment gallstones. | ||
* '''[[Neonatal jaundice]]''' — [[Hereditary spherocytosis|HS]] may present in the neonatal period with [[jaundice]] and hyperbilirubinemia, and the serum [[bilirubin]] level may not peak until several days after birth. Some experts have proposed that [[Hereditary spherocytosis|HS]] is underdiagnosed as a cause of [[neonatal jaundice]]. A requirement for [[phototherapy]] and/or [[exchange transfusion]] during this period is common. | * '''[[Neonatal jaundice]]''' — [[Hereditary spherocytosis|HS]] may present in the neonatal period with [[jaundice]] and hyperbilirubinemia, and the serum [[bilirubin]] level may not peak until several days after birth. Some experts have proposed that [[Hereditary spherocytosis|HS]] is underdiagnosed as a cause of [[neonatal jaundice]]. A requirement for [[phototherapy]] and/or [[exchange transfusion]] during this period is common. | ||
| Line 61: | Line 61: | ||
* '''Pigment gallstones''' — Pigment (bilirubin) [[gallstones]] are common in individuals with [[Hereditary spherocytosis|HS]] and may be the presenting finding in adults. [[Gallstones]] are unlikely before the age of 10 years but are seen in as many as half of adults, especially those with more severe [[hemolysis]]. [[Gallstones]] appear to be more common in individuals with [[Gilbert syndrome]]. | * '''Pigment gallstones''' — Pigment (bilirubin) [[gallstones]] are common in individuals with [[Hereditary spherocytosis|HS]] and may be the presenting finding in adults. [[Gallstones]] are unlikely before the age of 10 years but are seen in as many as half of adults, especially those with more severe [[hemolysis]]. [[Gallstones]] appear to be more common in individuals with [[Gilbert syndrome]]. | ||
=== Prognosis | === Prognosis === | ||
* Overall, the long-term outlook for people with [[hereditary spherocytosis]] (HS) is usually good with treatment. However, it may depend on the severity of the condition in each person. | * Overall, the long-term outlook for people with [[hereditary spherocytosis]] (HS) is usually good with treatment. However, it may depend on the severity of the condition in each person. | ||
* People with very mild [[Hereditary spherocytosis|HS]] may not have any signs or symptoms unless an environmental "trigger" causes symptom onset. In many cases, no specific therapy is needed other than monitoring for and watching for signs and symptoms.[8] Moderately and severely affected people are likely to benefit from splenectomy. | * People with very mild [[Hereditary spherocytosis|HS]] may not have any signs or symptoms unless an environmental "trigger" causes symptom onset. In many cases, no specific therapy is needed other than monitoring for and watching for signs and symptoms.[8] Moderately and severely affected people are likely to benefit from splenectomy. | ||
* Most people who undergo [[splenectomy]] are able to maintain a normal [[hemoglobin]] level.[4] However, people with severe [[Hereditary spherocytosis|HS]] may remain anemic post-splenectomy, and may need [[blood transfusions]] during an infection. | * Most people who undergo [[splenectomy]] are able to maintain a normal [[hemoglobin]] level.[4] However, people with severe [[Hereditary spherocytosis|HS]] may remain anemic post-splenectomy, and may need [[blood transfusions]] during an infection. | ||
== Diagnosis | == Diagnosis == | ||
=== Diagnostic Criteria | === Diagnostic Criteria === | ||
=== History and Symptoms | === History and Symptoms === | ||
* As in any other chronic hemolytic states, the signs and symptoms of [[Hereditary spherocytosis|hereditary spherocytosis (HS]]) include mild [[pallor]], intermittent [[jaundice]], and [[splenomegaly]]. However, signs and symptoms are highly variable. [[Anemia]] or [[hyperbilirubinemia]] may be of such magnitude as to require [[exchange transfusion]] in the neonatal period. The disorder also may escape clinical recognition altogether. [[Anemia]] usually is mild to moderate, but is sometimes very severe and sometimes not present. | * As in any other chronic hemolytic states, the signs and symptoms of [[Hereditary spherocytosis|hereditary spherocytosis (HS]]) include mild [[pallor]], intermittent [[jaundice]], and [[splenomegaly]]. However, signs and symptoms are highly variable. [[Anemia]] or [[hyperbilirubinemia]] may be of such magnitude as to require [[exchange transfusion]] in the neonatal period. The disorder also may escape clinical recognition altogether. [[Anemia]] usually is mild to moderate, but is sometimes very severe and sometimes not present. | ||
* Symptoms of hereditary spherocytosis include: | * Symptoms of hereditary spherocytosis include: | ||
| Line 80: | Line 80: | ||
** [[Weakness]] | ** [[Weakness]] | ||
=== Physical Examination | === Physical Examination === | ||
* [[Splenomegaly]] is the rule in [[Hereditary spherocytosis|HS]]. Palpable [[Spleen|spleens]] have been detected in more than 75% of affected subjects. The [[liver]] is normal in size and function. | * [[Splenomegaly]] is the rule in [[Hereditary spherocytosis|HS]]. Palpable [[Spleen|spleens]] have been detected in more than 75% of affected subjects. The [[liver]] is normal in size and function. | ||
| Line 86: | Line 86: | ||
* Any patient who presents with profound and sudden [[anemia]] and [[reticulocytopenia]] with the aforementioned physical findings also should have [[Hereditary spherocytosis|HS]] in the differential diagnosis. | * Any patient who presents with profound and sudden [[anemia]] and [[reticulocytopenia]] with the aforementioned physical findings also should have [[Hereditary spherocytosis|HS]] in the differential diagnosis. | ||
=== Laboratory Findings | === Laboratory Findings === | ||
'''Initial testing''' | '''Initial testing''' | ||
* '''CBC and RBC indices''' – All individuals with suspected [[Hereditary spherocytosis|HS]] based on [[family history]], [[neonatal jaundice]], or other findings should have a [[Complete blood count|complete blood count (CBC)]] with [[reticulocyte count]] and [[Red blood cell|red blood cell (RBC)]] indices. The [[Mean corpuscular hemoglobin concentration|mean corpuscular hemoglobin concentration (MCHC)]] is often the most useful parameter for assessing [[spherocytosis]]; an MCHC ≥36 g/dL is consistent with [[Spherocyte|spherocytes]]. A low [[Mean corpuscular volume|mean corpuscular volume (MCV)]] is also helpful in some cases, especially in [[neonates]], but variable degrees of [[reticulocytosis]] make the [[MCV]]<nowiki/>less useful in older children and adults. | *<nowiki/>'''CBC and RBC indices''' – All individuals with suspected [[Hereditary spherocytosis|HS]] based on [[family history]], [[neonatal jaundice]], or other findings should have a [[Complete blood count|complete blood count (CBC)]] with [[reticulocyte count]] and [[Red blood cell|red blood cell (RBC)]] indices. The [[Mean corpuscular hemoglobin concentration|mean corpuscular hemoglobin concentration (MCHC)]] is often the most useful parameter for assessing [[spherocytosis]]; an MCHC ≥36 g/dL is consistent with [[Spherocyte|spherocytes]]. A low [[Mean corpuscular volume|mean corpuscular volume (MCV)]] is also helpful in some cases, especially in [[neonates]], but variable degrees of [[reticulocytosis]] make the [[MCV]]<nowiki/>less useful in older children and adults. | ||
* '''[[Blood smear]] review''' – All individuals with suspected [[Hereditary spherocytosis|HS]] should have a [[blood smear]] reviewed by an experienced individual. In a [[peripheral blood smear]], the abnormally small [[Red blood cell|red blood cells]] lacking the central pallor i.e. spherocytes are seen. Other abnormal [[RBC]] shapes, and the degree of polychromatophilia, which reflects [[reticulocytosis]]. | * '''[[Blood smear]] review''' – All individuals with suspected [[Hereditary spherocytosis|HS]] should have a [[blood smear]] reviewed by an experienced individual. In a [[peripheral blood smear]], the abnormally small [[Red blood cell|red blood cells]] lacking the central pallor i.e. spherocytes are seen. Other abnormal [[RBC]] shapes, and the degree of polychromatophilia, which reflects [[reticulocytosis]]. | ||
* '''[[Coombs test|Coombs testing]]''' – If [[hemolysis]] is present, Coombs testing (also called direct antiglobulin testing [DAT]) is usually done to eliminate the possibility of immune-mediated hemolysis, which may be due to [[Hemolytic disease of newborn|hemolytic disease of the fetus and newborn (HDFN)]] in neonates or [[Autoimmune hemolytic anemia|autoimmune hemolytic anemia (AIHA)]] in older children and adults. The results of testing may also be useful to the [[transfusion]] service if [[transfusion]] is indicated. [[Coombs test|Coombs testing]] in [[Hereditary spherocytosis|HS]] is negative. | * '''[[Coombs test|Coombs testing]]''' – If [[hemolysis]] is present, Coombs testing (also called direct antiglobulin testing [DAT]) is usually done to eliminate the possibility of immune-mediated hemolysis, which <nowiki/>may be due to [[Hemolytic disease of newborn|hemolytic disease of the fetus and newborn (HDFN)]] in neonates or [[Autoimmune hemolytic anemia|autoimmune hemolytic anemia (AIHA)]] in older children and adults. The results of testing may also be useful to the [[transfusion]] service if [[transfusion]] is indicated. [[Coombs test|Coombs testing]] in [[Hereditary spherocytosis|HS]] is negative. | ||
'''Confirmatory tests''' | '''Confirmatory tests''' | ||
* '''EMA binding''' ●'''Osmotic fragility''' '''●Glycerol lysis''' ●'''Cryohemolysis''' | * '''EMA binding''' ●'''Osmotic fragility''' '''●Glycerol lysis''' ●'''Cryohemolysis''' | ||
=== Imaging Findings | === Imaging Findings === | ||
=== Other Diagnostic Studies | === Other Diagnostic Studies === | ||
== Treatment[edit | edit source] == | == Treatment[edit | edit source] == | ||
=== Medical Therapy | === Medical Therapy === | ||
* As with most inherited hemolytic anemias, treatment is directed at preventing or minimizing complications of chronic hemolysis and anemia. There are no specific treatments directed at the underlying red blood cell (RBC) membrane defect. | * As with most inherited hemolytic anemias, treatment is directed at preventing or minimizing complications of chronic hemolysis and anemia. There are no specific treatments directed at the underlying red blood cell (RBC) membrane defect. | ||
| Line 106: | Line 106: | ||
* The goals of pharmacotherapy for hereditary spherocytosis are to reduce morbidity and prevent complications. Folic acid supplementation is indicated to prevent megaloblastic crisis. | * The goals of pharmacotherapy for hereditary spherocytosis are to reduce morbidity and prevent complications. Folic acid supplementation is indicated to prevent megaloblastic crisis. | ||
=== Surgery | === Surgery === | ||
* Generally, the treatment of HS involves presplenectomy care, splenectomy, and management of postsplenectomy complications. | * Generally, the treatment of HS involves presplenectomy care, splenectomy, and management of postsplenectomy complications. | ||
* In pediatric cases, splenectomy ideally should not be performed until a child is older than 6 years because of the increased incidence of postsplenectomy infections with encapsulated organisms such as ''S pneumoniae'' and ''H influenzae'' in young children. | * In pediatric cases, splenectomy ideally should not be performed until a child is older than 6 years because of the increased incidence of postsplenectomy infections with encapsulated organisms such as ''S pneumoniae'' and ''H influenzae'' in young children. | ||
* Partial splenectomies are increasingly used in pediatric patients, as this approach appears to both control hemolysis and preserve splenic function. | * Partial splenectomies are increasingly used in pediatric patients, as this approach appears to both control hemolysis and preserve splenic function. | ||
=== Prevention | === Prevention === | ||
In general, once the diagnosis and baseline severity of HS in a child are established, it is not necessary to perform repeated blood tests unless there is an additional clinical indication (such as intercurrent infection and pallor, or an increase in jaundice). A routine annual review is usually sufficient together with an open door policy for potential complications such as parvovirus infection, or abdominal pain, which may trigger investigation for gallstones. | In general, once the diagnosis and baseline severity of HS in a child are established, it is not necessary to perform repeated blood tests unless there is an additional clinical indication (such as intercurrent infection and pallor, or an increase in jaundice). A routine annual review is usually sufficient together with an open door policy for potential complications such as parvovirus infection, or abdominal pain, which may trigger investigation for gallstones. | ||
Revision as of 16:41, 2 August 2018
Template:DiseaseDisorder infobox
|
Hereditary spherocytosis Microchapters |
|
Differentiating Hereditary spherocytosis from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Hereditary spherocytosis On the Web |
|
American Roentgen Ray Society Images of Hereditary spherocytosis |
|
Risk calculators and risk factors for Hereditary spherocytosis |
For patient information click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Hereditary spherocytosis is a genetically-transmitted form of spherocytosis, an auto-hemolytic anemia characterized by the production of red blood cells that are sphere-shaped rather than donut-shaped, and therefore more prone to hemolysis.
Historical Perspective
- Towards the end of the nineteenth century Vanlair and Masius described the case of a young woman who developed icterus, recurrent attacks of left upper quadrant abdominal pain and splenomegaly shortly after giving birth. The stools were not light coloured, but rather deeply pigmented. The patient's mother and sister were also icteric, and the sister's spleenwas enlarged.
Classification
- Hereditary Spherocytosis classified on basis of underlying defect in protein and also on the basis of severity of hemolysis.
Pathophysiology
There is intrinsic defects in erythrocyte membrane proteins that result in RBC cytoskeleton instability. Loss of erythrocyte surface area leads to the spherical shape of RBCs (spherocytes), which are culled rapidly from the circulation by the spleen. Hemolysis mainly confined to the spleen and, therefore, is extravascular. Splenomegaly commonly develops.
The following four abnormalities in RBC membrane proteins have been identified in HS:
- Spectrin deficiency alone
- Combined spectrin and ankyrin deficiency
- Band 3 deficiency
- Protein 4.2 defects
Causes
- HS is caused by a variety of mutations that lead to defects in red blood cell (RBC) membrane proteins. HS usually is transmitted as an autosomal dominant trait, and the identification of the disorder in multiple generations of affected families is the rule. Homozygosity for this dominantly transmitted HS gene has not been identified, which suggests that the homozygous state is incompatible with life.
Differentiating Hereditary spherocytosis overview from Other Diseases
Epidemiology and Demographics
- HS is seen in all populations but appears to be especially common in people of northern European ancestry.
- In the United States, the incidence of the disorder is approximately one case in 5000 people.
- In northern European, HS affects as many as 1 in 2000 to 1 in 5000 (prevalence, approximately 0.02 to 0.05 percent).
Risk Factors
- The risk factors for this condition have not yet been properly identified.
- However, having a family member with this condition can increase your susceptibility to this disease. The condition is also most common in individuals of North European origin although it has been found to arise in people of all races.
Screening
- It is also important to test newborns of affected parents for HS, as affected newborns may have severe hyperbilirubinemia and anemia. This may be done by a clinician with expertise in hemolytic anemias or by a genetic counselor. It is possible for an individual with no hemolysis, no spherocytes on the blood smear, and a normal reticulocyte count to be a carrier of HS, which may be relevant in certain families.
Natural History, Complications, and Prognosis
Natural History
- Disease severity and age of presentation — HS can present at any age and with any severity, with case reports describing a range of presentations, from hydrops fetalis in utero through diagnosis in the ninth decade of life.
- The majority of affected individuals have mild or moderate hemolysis or hemolytic anemia and a known family history, making diagnosis and treatment relatively straightforward. Individuals with significant severe hemolysis may develop additional complications such as jaundice/hyperbilirubinemia, folate deficiency, or splenomegaly.
Complications
Common complications of hemolysis include neonatal jaundice, splenomegaly, and pigment gallstones.
- Neonatal jaundice — HS may present in the neonatal period with jaundice and hyperbilirubinemia, and the serum bilirubin level may not peak until several days after birth. Some experts have proposed that HS is underdiagnosed as a cause of neonatal jaundice. A requirement for phototherapy and/or exchange transfusion during this period is common.
- Splenomegaly — Splenomegaly is rare in neonates, but can often be seen in older children and adults with HS. Early reports of family studies found palpable spleens in over three-fourths of affected members, but this may reflect a skewed population with the most severe disease. In these studies, the relationship between disease severity and splenic size was not linear.
- Pigment gallstones — Pigment (bilirubin) gallstones are common in individuals with HS and may be the presenting finding in adults. Gallstones are unlikely before the age of 10 years but are seen in as many as half of adults, especially those with more severe hemolysis. Gallstones appear to be more common in individuals with Gilbert syndrome.
Prognosis
- Overall, the long-term outlook for people with hereditary spherocytosis (HS) is usually good with treatment. However, it may depend on the severity of the condition in each person.
- People with very mild HS may not have any signs or symptoms unless an environmental "trigger" causes symptom onset. In many cases, no specific therapy is needed other than monitoring for and watching for signs and symptoms.[8] Moderately and severely affected people are likely to benefit from splenectomy.
- Most people who undergo splenectomy are able to maintain a normal hemoglobin level.[4] However, people with severe HS may remain anemic post-splenectomy, and may need blood transfusions during an infection.
Diagnosis
Diagnostic Criteria
History and Symptoms
- As in any other chronic hemolytic states, the signs and symptoms of hereditary spherocytosis (HS) include mild pallor, intermittent jaundice, and splenomegaly. However, signs and symptoms are highly variable. Anemia or hyperbilirubinemia may be of such magnitude as to require exchange transfusion in the neonatal period. The disorder also may escape clinical recognition altogether. Anemia usually is mild to moderate, but is sometimes very severe and sometimes not present.
- Symptoms of hereditary spherocytosis include:
- Yellowing of the skin and eyes (jaundice)
- Pale coloring (pallor)
- Fatigue
- Irritability
- Shortness of breath
- Weakness
Physical Examination
- Splenomegaly is the rule in HS. Palpable spleens have been detected in more than 75% of affected subjects. The liver is normal in size and function.
- Other important clues are jaundice and upper right abdominal pain indicative of gallbladder disease. This is especially important if the patient has a family history of gallbladder disease.
- Any patient who presents with profound and sudden anemia and reticulocytopenia with the aforementioned physical findings also should have HS in the differential diagnosis.
Laboratory Findings
Initial testing
- CBC and RBC indices – All individuals with suspected HS based on family history, neonatal jaundice, or other findings should have a complete blood count (CBC) with reticulocyte count and red blood cell (RBC) indices. The mean corpuscular hemoglobin concentration (MCHC) is often the most useful parameter for assessing spherocytosis; an MCHC ≥36 g/dL is consistent with spherocytes. A low mean corpuscular volume (MCV) is also helpful in some cases, especially in neonates, but variable degrees of reticulocytosis make the MCVless useful in older children and adults.
- Blood smear review – All individuals with suspected HS should have a blood smear reviewed by an experienced individual. In a peripheral blood smear, the abnormally small red blood cells lacking the central pallor i.e. spherocytes are seen. Other abnormal RBC shapes, and the degree of polychromatophilia, which reflects reticulocytosis.
- Coombs testing – If hemolysis is present, Coombs testing (also called direct antiglobulin testing [DAT]) is usually done to eliminate the possibility of immune-mediated hemolysis, which may be due to hemolytic disease of the fetus and newborn (HDFN) in neonates or autoimmune hemolytic anemia (AIHA) in older children and adults. The results of testing may also be useful to the transfusion service if transfusion is indicated. Coombs testing in HS is negative.
Confirmatory tests
- EMA binding ●Osmotic fragility ●Glycerol lysis ●Cryohemolysis
Imaging Findings
Other Diagnostic Studies
Treatment[edit | edit source]
Medical Therapy
- As with most inherited hemolytic anemias, treatment is directed at preventing or minimizing complications of chronic hemolysis and anemia. There are no specific treatments directed at the underlying red blood cell (RBC) membrane defect.
- If a neonate is suspected of having HS (eg, based on positive family history and neonatal jaundice), treatment can be initiated for HS without awaiting diagnostic confirmation. This may include therapy for hyperbilirubinemia and, in severe cases, transfusion or even exchange transfusion [83
- The goals of pharmacotherapy for hereditary spherocytosis are to reduce morbidity and prevent complications. Folic acid supplementation is indicated to prevent megaloblastic crisis.
Surgery
- Generally, the treatment of HS involves presplenectomy care, splenectomy, and management of postsplenectomy complications.
- In pediatric cases, splenectomy ideally should not be performed until a child is older than 6 years because of the increased incidence of postsplenectomy infections with encapsulated organisms such as S pneumoniae and H influenzae in young children.
- Partial splenectomies are increasingly used in pediatric patients, as this approach appears to both control hemolysis and preserve splenic function.
Prevention
In general, once the diagnosis and baseline severity of HS in a child are established, it is not necessary to perform repeated blood tests unless there is an additional clinical indication (such as intercurrent infection and pallor, or an increase in jaundice). A routine annual review is usually sufficient together with an open door policy for potential complications such as parvovirus infection, or abdominal pain, which may trigger investigation for gallstones.