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'''For patient information click [[Hereditary spherocytosis (patient information)|here]]'''
'''For patient information click [[Hereditary spherocytosis (patient information)|here]]'''


{{CMG}} {{ZAS}}
{{CMG}}; {{AE}} {{ZAS}}


==[[Hereditary spherocytosis overview|Overview]]==
==[[Hereditary spherocytosis overview|Overview]]==
'''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 ==
== [[hereditary spherocytosis historical perspective|Historical Perspective]] ==
* Hereditary spherocytosis was first described in 1871.<ref>{{Cite journal
| author = [[Sayeeda Huq]], [[Mark A. C. Pietroni]], [[Hafizur Rahman]] & [[Mohammad Tariqul Alam]]
| title = Hereditary spherocytosis
| journal = [[Journal of health, population, and nutrition]]
| volume = 28
| issue = 1
| pages = 107–109
| year = 2010
| month = February
| pmid = 20214092
}}</ref>
* It is the commonest cause of inherited chronic hemolysis in the northern europe and north america.<ref>{{Cite journal
| author = [[Sayeeda Huq]], [[Mark A. C. Pietroni]], [[Hafizur Rahman]] & [[Mohammad Tariqul Alam]]
| title = Hereditary spherocytosis
| journal = [[Journal of health, population, and nutrition]]
| volume = 28
| issue = 1
| pages = 107–109
| year = 2010
| month = February
| pmid = 20214092
}}</ref>


== Classification ==
== [[hereditary spherocytosis classification|Classification]] ==
* Hereditary Spherocytosis classified on basis of underlying defect in protein and also on the basis of severity of hemolysis.
* Classification of hereditary spherocytosis on the basis of clinical severity.<ref name="Bolton-Maggs2004">{{cite journal|last1=Bolton-Maggs|first1=P H B|title=Hereditary spherocytosis; new guidelines|journal=Archives of Disease in Childhood|volume=89|issue=9|year=2004|pages=809–812|issn=0003-9888|doi=10.1136/adc.2003.034587}}</ref>{{cite web |url=http://www.ncbi.nlm.nih.gov/books/NBK1116/ |title=GeneReviews® - NCBI Bookshelf |format= |work= |accessdate=}}


{| class="wikitable"
== [[hereditary spherocytosis pathophysiology|Pathophysiology]] ==
|+
! Locus
! Gene
! Protein
! Inheritance
! Severity
! Comment
|-
| SPH1
| ANK1
| Ankyrin-1
| AD/AR
| mild-moderate/moderately severe-severe
| often transfusion dependant
|-
| SPH2
| SPTB
| Spectrin beta chain,erythrocytic
| AD/AR
| mild-moderate/severe
| 1 fatal infantile case described
|-
| SPH3
| SPTA1
| Spectrin alpha chain,erythrocytic1
| AR
| severe
| transfusion dependant
|-
| SPH4
| SLC4A1
| Band3(anion transport protein)
| AD
| mild-moderate
| certain SLC4A1 variants cause disease only when biallelic
|-
| SPH5
| EPB42
| Protein 4.2
| AR
| mild-moderate
| 1 moderately severe case described
|}
{| class="wikitable"
|+
! Classification
! Mild
! Moderate
! Severe
|-
! Hemoglobin (g/dl)
| 110-150
| 80-120
| 60-80
|-
! Reticulocyte count (%)
| 3-6
| >6
| >10
|-
! Bilirubin (ug/l)
| 17-34
| >34
| >51
|-
! Splenectomy
| usually not required
| indicated during school age, usually before puberty
| necessary - delay until 6 years of age if possible
|}


== Pathophysiology ==
== [[hereditary spherocytosis causes|Causes]] ==
* The defects in hereditary spherocytosis lie in the cell membrane.<ref name="Bolton-Maggs2004">{{cite journal|last1=Bolton-Maggs|first1=P H B|title=Hereditary spherocytosis; new guidelines|journal=Archives of Disease in Childhood|volume=89|issue=9|year=2004|pages=809–812|issn=0003-9888|doi=10.1136/adc.2003.034587}}</ref>
* The proteins essential for integrity of membrane structure lie immediately under the lipid bilayer, horizental aplha & beta spectrin molecules form heterodimers with linkage to vertical elements- ankyrin, proteins 4.1 & 4.2 and band 3 (a transmembrane protein).
* Different genes code for each of these proteins, therefore hereditary spherocytosis is a hetrogenous disorder which can result from a defect in any one of these proteins.
* The destabilization of membrane leads to both abnormal morphology and reduced red cell life span.
* The shorter the life span of red blood cells, the worse the clinical effects.
* Genetic defect and clinical severity tend to be fairly constant within a given family,but between family varies from mild asymptomatic hemolysis to severe continuous anemia with jaundice.


== Causes ==
== [[Hereditary spherocytosis differential diagnosis|Differentiating Hereditary Spherocytosis from Other Diseases]] ==
* Hereditary spherocytosis is caused by a variety of genetic mutations.<ref name="HeLiao2018">{{cite journal|last1=He|first1=Ben-Jin|last2=Liao|first2=Lin|last3=Deng|first3=Zeng-Fu|last4=Tao|first4=Yi-Feng|last5=Xu|first5=Yu-Chan|last6=Lin|first6=Fa-Quan|title=Molecular Genetic Mechanisms of Hereditary Spherocytosis: Current Perspectives|journal=Acta Haematologica|volume=139|issue=1|year=2018|pages=60–66|issn=0001-5792|doi=10.1159/000486229}}</ref><ref name="PerrottaGallagher2008">{{cite journal|last1=Perrotta|first1=Silverio|last2=Gallagher|first2=Patrick G|last3=Mohandas|first3=Narla|title=Hereditary spherocytosis|journal=The Lancet|volume=372|issue=9647|year=2008|pages=1411–1426|issn=01406736|doi=10.1016/S0140-6736(08)61588-3}}</ref>
* There are 05 genes associated with hereditary spherocytosis including, alpha spectrin (SPTA1), beta spectrin (SPTB), ankyrin (ANK1), band3 (SLC4A1) and protein 4.2 (EPB42).
* Mutations in one or more of hereditary spherocytosis related genes can cause membrane protein deficiency leading to hereditary spherocytosis.
{| class="wikitable"
|+Molecular and Genetic Characteristics of 5 Erythrocyte Membrane Protein Genes
! Gene
! Chromosome Location
! Membrane Protein
! Prevalent Mutations
! Heredity
! Associated Disease
|-
| ANK1
|8p11.2
| Ankyrin-1
| frameshift, nonsense, splicing, novel mutations
| autosomal dominant, autosomal recessive
| hereditary spherocytosis
|-
| SLC4A1
| 17q21
| Band3
| missense,frameshift,polymorphism
| autosomal dominant
| hereditary spherocytosis,distal renal tubular acisosis
|-
| SPTA1
| 1q22-q23
| alpha spectrin
| SpaLEPRA allele, splicing, frameshift
| autosomal recessive
| hereditary spherocytosis, hereditary eliptocytosis, hereditary pyropoikilocytosis
|-
| SPTB
| 14q23-q24.1
| beta spectrin
| splicing, frameshift, nonsense, novel mutations
| autosomal dominant
| hereditary spherocytosis, hereditary eliptocytosis, hereditary pyropoikilocytosis
|-
| EBP42
| 15q15-q21
| protein 4.2
| missense, nonsense
| autosomal recessive
| hereditary spherocytosis
|}


== Differentiating Hereditary Spherocytosis from Other Diseases ==
== [[hereditary spherocytosis epidemiology and demographics|Epidemiology and Demographics]] ==
* Hereditary spherocytosis presents with hemolysis, therefore should be differentiated from following diseases.<ref>{{Cite journal
| author = [[Robert D. Christensen]], [[Hassan M. Yaish]] & [[Patrick G. Gallagher]]
| title = A pediatrician's practical guide to diagnosing and treating hereditary spherocytosis in neonates
| journal = [[Pediatrics]]
| volume = 135
| issue = 6
| pages = 1107–1114
| year = 2015
| month = June
| doi = 10.1542/peds.2014-3516
| pmid = 26009624
}}</ref><ref name="PerrottaGallagher2008">{{cite journal|last1=Perrotta|first1=Silverio|last2=Gallagher|first2=Patrick G|last3=Mohandas|first3=Narla|title=Hereditary spherocytosis|journal=The Lancet|volume=372|issue=9647|year=2008|pages=1411–1426|issn=01406736|doi=10.1016/S0140-6736(08)61588-3}}</ref>
** Autoimmune hemolysis
** Thermal injury
** Clostridial septicemia
** Wilson disease
** Hemoglobinopathies
** Hereditary stomatocytosis
** Congenital dyserythrpoietic anemia type II


== Epidemiology and Demographics ==
== [[hereditary spherocytosis risk factors|Risk Factors]] ==
* Hereditary spherocytosis is reported worldwide in all racial and ethnic groups.<ref>{{Cite journal
| author = [[Silverio Perrotta]], [[Patrick G. Gallagher]] & [[Narla Mohandas]]
| title = Hereditary spherocytosis
| journal = [[Lancet (London, England)]]
| volume = 372
| issue = 9647
| pages = 1411–1426
| year = 2008
| month = October
| doi = 10.1016/S0140-6736(08)61588-3
| pmid = 18940465
}}</ref>
* It is the most common inherited anemia in the northern European ancestry and north america.<ref>{{Cite journal
| author = [[Sayeeda Huq]], [[Mark A. C. Pietroni]], [[Hafizur Rahman]] & [[Mohammad Tariqul Alam]]
| title = Hereditary spherocytosis
| journal = [[Journal of health, population, and nutrition]]
| volume = 28
| issue = 1
| pages = 107–109
| year = 2010
| month = February
| pmid = 20214092
}}</ref>
* The reported incidence of hereditary spherocytosis is 1 in 2000 births.<ref>{{Cite journal
| author = [[Sayeeda Huq]], [[Mark A. C. Pietroni]], [[Hafizur Rahman]] & [[Mohammad Tariqul Alam]]
| title = Hereditary spherocytosis
| journal = [[Journal of health, population, and nutrition]]
| volume = 28
| issue = 1
| pages = 107–109
| year = 2010
| month = February
| pmid = 20214092
}}</ref>
* It is less commonly seen in african american and southeast asian people.<ref name="PerrottaGallagher2008">{{cite journal|last1=Perrotta|first1=Silverio|last2=Gallagher|first2=Patrick G|last3=Mohandas|first3=Narla|title=Hereditary spherocytosis|journal=The Lancet|volume=372|issue=9647|year=2008|pages=1411–1426|issn=01406736|doi=10.1016/S0140-6736(08)61588-3}}</ref>


== Risk Factors ==
== [[hereditary spherocytosis screening|Screening]] ==
* A positive family history is an important risk factor for hereditary spherocytosis, as it is an inherited condition.<ref>{{Cite journal
| author = [[Sayeeda Huq]], [[Mark A. C. Pietroni]], [[Hafizur Rahman]] & [[Mohammad Tariqul Alam]]
| title = Hereditary spherocytosis
| journal = [[Journal of health, population, and nutrition]]
| volume = 28
| issue = 1
| pages = 107–109
| year = 2010
| month = February
| pmid = 20214092
}}</ref>
* There are no other risk factors have been clearly identified for this condition.


== Screening ==
== [[hereditary spherocytosis natural history, complications and prognosis|Natural History, Complications, and Prognosis]] ==
* The screening test used for hereditary spherocytosis is automated mean cell hemoglobin concentration (MCHC).<ref>{{Cite journal
| author = [[L. A. Michaels]], [[A. R. Cohen]], [[H. Zhao]], [[R. I. Raphael]] & [[C. S. Manno]]
| title = Screening for hereditary spherocytosis by use of automated erythrocyte indexes
| journal = [[The Journal of pediatrics]]
| volume = 130
| issue = 6
| pages = 957–960
| year = 1997
| month = June
| pmid = 9202619
}}</ref>
* Erythrocyte distribution width when raised is also useful as a powerful screening test.<ref>{{Cite journal
| author = [[Silvia Eandi Eberle]], [[Gabriela Sciuccati]], [[Mariana Bonduel]], [[Lilian Diaz]], [[Raquel Staciuk]] & [[Aurora Feliu Torres]]
| title = &#91;Erythrocyte indexes in hereditary spherocytosis&#93;
| journal = [[Medicina]]
| volume = 67
| issue = 6 Pt 2
| pages = 698–700
| year = 2007
| month =
| pmid = 18422060
}}</ref>
* The combination of these two tests (MCHC & erythrocyte distribution width) is an excellent predictor for the diagnosis of hereditary spherocytosis.<ref name="MichaelsCohen1997">{{cite journal|last1=Michaels|first1=Lisa A.|last2=Cohen|first2=Alan R.|last3=Zhao|first3=Huaqing|last4=Raphael|first4=Robert I.|last5=Manno|first5=Catherine S.|title=Screening for hereditary spherocytosis by use of automated erythrocyte indexes|journal=The Journal of Pediatrics|volume=130|issue=6|year=1997|pages=957–960|issn=00223476|doi=10.1016/S0022-3476(97)70283-X}}</ref>


== Natural History, Complications, and Prognosis ==
== [[hereditary spherocytosis diagnostic study of choice|Diagnosis]] ==


=== Natural History ===
== [[Hereditary spherocytosis history and symptoms|History and Symptoms]] ==
* The clinical course of hereditary spherocytosis is variable depending upon the severity of disease.<ref>{{Cite journal
| author = [[Olga Ciepiela]]
| title = Old and new insights into the diagnosis of hereditary spherocytosis
| journal = [[Annals of translational medicine]]
| volume = 6
| issue = 17
| pages = 339
| year = 2018
| month = September
| doi = 10.21037/atm.2018.07.35
| pmid = 30306078
}}</ref>
* During infancy, hemoglobin level falls rapidly after 20 days of birth leading to transient & severe anemia, causing inappropriate erythrocyte response and splenic filtering function.<ref>{{Cite journal
| author = [[F. Delhommeau]], [[T. Cynober]], [[P. O. Schischmanoff]], [[P. Rohrlich]], [[J. Delaunay]], [[N. Mohandas]] & [[G. Tchernia]]
| title = Natural history of hereditary spherocytosis during the first year of life
| journal = [[Blood]]
| volume = 95
| issue = 2
| pages = 393–397
| year = 2000
| month = January
| pmid = 10627440
}}</ref>
* About 20-30% of patients have mild disease with compensated hemolysis.
* About 60-70% of patients have moderate disease, presenting in childhood but can present at any age.
* About 3-5% of patients have severe hereditary disease with life threatening anemia, requiring regular transfusions to maintain a hemoglobin concentration of greater than 60g/L.
* Without regular transfusions or splenectomy or both, patients may develop kernicterus, severe hemolytic anemia, gallstones, growth retardation, delayed sexual maturation, extramedullary hematopoiesis with hepatosplenomegaly and bony changes (thalassemic facies).<ref name="PerrottaGallagher2008">{{cite journal|last1=Perrotta|first1=Silverio|last2=Gallagher|first2=Patrick G|last3=Mohandas|first3=Narla|title=Hereditary spherocytosis|journal=The Lancet|volume=372|issue=9647|year=2008|pages=1411–1426|issn=01406736|doi=10.1016/S0140-6736(08)61588-3}}</ref>


=== Complications ===
== [[hereditary spherocytosis physical examination|Physical Examination]] ==
* The complications of hereditary spherocytosis include:<ref>{{Cite journal
| author = [[Sayeeda Huq]], [[Mark A. C. Pietroni]], [[Hafizur Rahman]] & [[Mohammad Tariqul Alam]]
| title = Hereditary spherocytosis
| journal = [[Journal of health, population, and nutrition]]
| volume = 28
| issue = 1
| pages = 107–109
| year = 2010
| month = February
| pmid = 20214092
}}</ref><ref name="FriedmanWilliams1988">{{cite journal|last1=Friedman|first1=Ellen Wolkin|last2=Williams|first2=Jeannine C.|last3=van Hook|first3=Lucille|title=Hereditary spherocytosis in the elderly|journal=The American Journal of Medicine|volume=84|issue=3|year=1988|pages=513–516|issn=00029343|doi=10.1016/0002-9343(88)90275-6}}</ref><ref name="GuittonGarçon2008">{{cite journal|last1=Guitton|first1=C.|last2=Garçon|first2=L.|last3=Cynober|first3=T.|last4=Gauthier|first4=F.|last5=Tchernia|first5=G.|last6=Delaunay|first6=J.|last7=Leblanc|first7=T.|last8=Thuret|first8=I.|last9=Bader-Meunier|first9=B.|title=Sphérocytose héréditaire : recommandations pour le diagnostic et la prise en charge chez l’enfant|journal=Archives de Pédiatrie|volume=15|issue=9|year=2008|pages=1464–1473|issn=0929693X|doi=10.1016/j.arcped.2008.04.023}}</ref>
** hemolytic anemia
** jaundice
** kernicterus
** cholelithiasis
** hemolytic, aplastic and megaloblastic crises
** growth failure
** leg ulcers
** skeletal abnormalities resulting from bone marrow expansion
** multiple myeloma
** leukemia


=== Prognosis ===
== [[hereditary spherocytosis laboratory findings|Laboratory Findings]] ==
* The prognosis of patients with hereditary spherocytosis is usually good with early diagnosis, regular followup and management.<ref>{{Cite journal
| author = [[Yuki Tateno]], [[Ryoji Suzuki]] & [[Yukihiro Kitamura]]
| title = Previously undiagnosed hereditary spherocytosis in a patient with jaundice and pyelonephritis: a case report
| journal = [[Journal of medical case reports]]
| volume = 10
| issue = 1
| pages = 337
| year = 2016
| month = December
| doi = 10.1186/s13256-016-1144-8
| pmid = 27906107
}}</ref>
* Patients with hereditary spherocytosis may remain undiagnosed for years if their hemolysis is mild.


== Diagnosis ==
== [[hereditary spherocytosis chest x ray|Chest X ray]] ==


=== Diagnostic Criteria ===
== [[hereditary spherocytosis CT|CT]] ==
* The diagnosis of hereditary spherocytosis can be based on the physical examination, complete red cell count, recticulocyte count, medical history and specific tests, preferentially, the EMA (eosin-5-maleimide binding) test and AGLT (acidified glycerol lysis time).<ref name="GuittonGarçon2008">{{cite journal|last1=Guitton|first1=C.|last2=Garçon|first2=L.|last3=Cynober|first3=T.|last4=Gauthier|first4=F.|last5=Tchernia|first5=G.|last6=Delaunay|first6=J.|last7=Leblanc|first7=T.|last8=Thuret|first8=I.|last9=Bader-Meunier|first9=B.|title=Sphérocytose héréditaire : recommandations pour le diagnostic et la prise en charge chez l’enfant|journal=Archives de Pédiatrie|volume=15|issue=9|year=2008|pages=1464–1473|issn=0929693X|doi=10.1016/j.arcped.2008.04.023}}</ref><ref>{{Cite journal
| author = [[Sayeeda Huq]], [[Mark A. C. Pietroni]], [[Hafizur Rahman]] & [[Mohammad Tariqul Alam]]
| title = Hereditary spherocytosis
| journal = [[Journal of health, population, and nutrition]]
| volume = 28
| issue = 1
| pages = 107–109
| year = 2010
| month = February
| pmid = 20214092
}}</ref>
* The diagnosis can be made at any age, including the neonatal period from day of birth.<ref>{{Cite journal
| author = [[Yuki Tateno]], [[Ryoji Suzuki]] & [[Yukihiro Kitamura]]
| title = Previously undiagnosed hereditary spherocytosis in a patient with jaundice and pyelonephritis: a case report
| journal = [[Journal of medical case reports]]
| volume = 10
| issue = 1
| pages = 337
| year = 2016
| month = December
| doi = 10.1186/s13256-016-1144-8
| pmid = 27906107
}}</ref>
* The diagnostic guidelines of hereditary spherocytosis from the British Committee for Standards in hematology do not recommend any additional tests for patients with classical clinical features and laboratory data.
* The eosin-5-maleimide (EMA) binding test has high sensitivity (92–93%) and specificity (99%) for hereditary spherocytosis, although a positive test can also be obtained in patients affected by related conditions, such as congenital dyserythropoietic anemia type II (CDA II)
* Other tests, such as the osmotic fragility (OF) test, acidified glycerol lysis test (AGLT) and the pink test, exhibit lower sensitivity compared to the EMA test (68%, 61% and 91%, respectively).<ref>{{Cite journal
| author = [[Immacolata Andolfo]], [[Roberta Russo]], [[Antonella Gambale]] & [[Achille Iolascon]]
| title = New insights on hereditary erythrocyte membrane defects
| journal = [[Haematologica]]
| volume = 101
| issue = 11
| pages = 1284–1294
| year = 2016
| month = November
| doi = 10.3324/haematol.2016.142463
| pmid = 27756835
}}</ref>
* Ektacytometry is a highly sensitive test of membrane deformability.


== [[hereditary spherocytosis MRI|MRI]] ==


== [[hereditary spherocytosis echocardiography or ultrasound| Echocardiography or Ultrasound]] ==


{| class="wikitable"
== [[hereditary spherocytosis other imaging findings|Other Imaging Findings]] ==
|+
Simple Diagnostic Criteria to evoke the Diagnosis of Hereditary Spherocytosis
! Clinical Parameters
| pallor, splenomegaly, inconstant jaundice
|-
! Biological paraneters & erythrocyte indices
| dec Hb, inc MCHC, inc %hyperdense cells, inc reticulocytes
|-
! Blood smear
| Spherocytes (may be absent)
|-
! Signs of hemolysis
| inc free bilirubin, dec haptoglobin, inc reticulocytes
|-
! Erythrocyte coombs test
| negative
|}


{| class="wikitable"
== [[hereditary spherocytosis other diagnostic studies|Other Diagnostic Studies]] ==
|+
Specific Biological Examinations for the Diagnosis of Hereditary Spherocytosis
! Tests
! Principle/feasibility
! Sensitivity/Specificity
|-
| Osmotic resistance
| hemolysis test/routime examination
| 66%/low
|-
| Pink test
| hemolysis test/simple test time-out test <3 hours
| 96%/79-94%
|-
| AGLT
| Hemolysis test time of test >3 hours
| 81%/95%
|-
| Ektacytometry in osmolar gradient
| study of deformity of RBCs single laboratory in France test execution time:24 hours
| reference exam
|-
| Flow cytometry
| labeling of RBCs with eosin 5 maleimide/not available on routine basis test run time >48 h
| Being evaluated
|}


=== History and Symptoms ===
== [[hereditary spherocytosis medical therapy|Treatment]] ==
* Hereditary spherocytosis is a familial hemolytic disorder with marked heterogeneity.<ref>{{Cite journal
| author = [[Yuki Tateno]], [[Ryoji Suzuki]] & [[Yukihiro Kitamura]]
| title = Previously undiagnosed hereditary spherocytosis in a patient with jaundice and pyelonephritis: a case report
| journal = [[Journal of medical case reports]]
| volume = 10
| issue = 1
| pages = 337
| year = 2016
| month = December
| doi = 10.1186/s13256-016-1144-8
| pmid = 27906107
}}</ref><ref>{{Cite journal
| author = [[Maria Christina Lopes Araujo Oliveira]], [[Rachel Aparecida Ferreira Fernandes]], [[Carolina Lins Rodrigues]], [[Daniela Aguiar Ribeiro]], [[Maria Fernanda Giovanardi]] & [[Marcos Borato Viana]]
| title = Clinical course of 63 children with hereditary spherocytosis: a retrospective study
| journal = [[Revista brasileira de hematologia e hemoterapia]]
| volume = 34
| issue = 1
| pages = 9–13
| year = 2012
| month =
| doi = 10.5581/1516-8484.20120006
| pmid = 23049376
}}</ref><ref>{{Cite journal
| author = [[Immacolata Andolfo]], [[Roberta Russo]], [[Antonella Gambale]] & [[Achille Iolascon]]
| title = New insights on hereditary erythrocyte membrane defects
| journal = [[Haematologica]]
| volume = 101
| issue = 11
| pages = 1284–1294
| year = 2016
| month = November
| doi = 10.3324/haematol.2016.142463
| pmid = 27756835
}}</ref>
* Clinical features range from asymptomatic to fulminant hemolytic anemia.<ref>{{Cite journal
| author = [[Sayeeda Huq]], [[Mark A. C. Pietroni]], [[Hafizur Rahman]] & [[Mohammad Tariqul Alam]]
| title = Hereditary spherocytosis
| journal = [[Journal of health, population, and nutrition]]
| volume = 28
| issue = 1
| pages = 107–109
| year = 2010
| month = February
| pmid = 20214092
}}</ref>
* Symptoms and history of hereditary spherocytosis include;
** hemolysis
** anemia
** jaundice
** weakness
** irritability
** shortness of breath
** pallor
** thrombocytopenia
** pyelonephritis
** hyperbilirubinemia


=== Physical Examination ===
== [[hereditary spherocytosis medical therapy|Medical Therapy]] ==
* The physical examination findings in hereditary spherocytosis include;<ref name="PerrottaGallagher2008">{{cite journal|last1=Perrotta|first1=Silverio|last2=Gallagher|first2=Patrick G|last3=Mohandas|first3=Narla|title=Hereditary spherocytosis|journal=The Lancet|volume=372|issue=9647|year=2008|pages=1411–1426|issn=01406736|doi=10.1016/S0140-6736(08)61588-3}}</ref>
** scleral icterus
** jaundice
** splenomegaly


=== Laboratory Findings ===
== [[hereditary spherocytosis surgery|Surgery]] ==
'''Initial testing'''
*<nowiki/>'''CBC and RBC indices''' - The mean cell hemoglobin concentration (MCHC) and red cell distribution width (RDW) are both raised in hereditary spherocytosis.<ref name="Farias2017">{{cite journal|last1=Farias|first1=Mariela Granero|title=Advances in laboratory diagnosis of hereditary spherocytosis|journal=Clinical Chemistry and Laboratory Medicine (CCLM)|volume=55|issue=7|year=2017|issn=1437-4331|doi=10.1515/cclm-2016-0738}}</ref>
* '''[[Blood smear]] review''' – shows the spherocytes and increased reticulocytes.
* '''[[Coombs test|Coombs testing]]''' – used when hemolysis is present, to differentiate hereditary spherocytosis from autoimmune hemolytic anemia (AIHA). Coombs test is negative in hereditary spherocytosis.
'''Confirmatory tests'''
** EMA (eosin 5 maleimide binding assay) test<ref>{{Cite journal
| author = [[Olga Ciepiela]]
| title = Old and new insights into the diagnosis of hereditary spherocytosis
| journal = [[Annals of translational medicine]]
| volume = 6
| issue = 17
| pages = 339
| year = 2018
| month = September
| doi = 10.21037/atm.2018.07.35
| pmid = 30306078
}}</ref><ref>{{Cite journal
| author = [[Paola Bianchi]], [[Elisa Fermo]], [[Cristina Vercellati]], [[Anna P. Marcello]], [[Laura Porretti]], [[Agostino Cortelezzi]], [[Wilma Barcellini]] & [[Alberto Zanella]]
| title = Diagnostic power of laboratory tests for hereditary spherocytosis: a comparison study in 150 patients grouped according to molecular and clinical characteristics
| journal = [[Haematologica]]
| volume = 97
| issue = 4
| pages = 516–523
| year = 2012
| month = April
| doi = 10.3324/haematol.2011.052845
| pmid = 22058213
}}</ref>
** Osmotic fragility test
** Acidified glycerol lysis test
** Cryohemolysis
** Plasma membrane protein electrophoresis


=== Imaging Findings: ===
==[[hereditary spherocytosis primary prevention|Primary Prevention]] ==
* There are no particular other imaging findings associated with HS.


=== Other Diagnostic Studies: ===
== [[hereditary spherocytosis secondary prevention|Secondary Prevention]]==
** There are no other diagnostic tests available for the hereditary spherocytosis.


== Treatment ==
== [[hereditary spherocytosis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] ==


=== Medical Therapy ===
== [[hereditary spherocytosis future or investigational therapies|Future or Investigational Therapies]] ==
* There is no specific medical therapy for hereditary spherocytosis. As the diagnosis of hereditary spherocytosis is made, surveillance is needed to help detect and manage any complications.<ref name="Bolton-MaggsStevens2004">{{cite journal|last1=Bolton-Maggs|first1=P. H. B.|last2=Stevens|first2=R. F.|last3=Dodd|first3=N. J.|last4=Lamont|first4=G.|last5=Tittensor|first5=P.|last6=King|first6=M.-J.|title=Guidelines for the diagnosis and management of hereditary spherocytosis|journal=British Journal of Haematology|volume=126|issue=4|year=2004|pages=455–474|issn=0007-1048|doi=10.1111/j.1365-2141.2004.05052.x}}</ref>


* A routine annual review is usually sufficient to detect any complications such as parvovirus infection or abdominal pain which may necessitate the investigation for gallstones.
== [[Hereditary spherocytosis case study one|Case Studies]] ==
* Folate supplementation is not always required, but is used as a routine for children with severe hemolysis and in pregnancy, regardless of severity of hereditary spherocytosis.<ref>{{Cite journal
| author = [[P. H. B. Bolton-Maggs]]
| title = Hereditary spherocytosis; new guidelines
| journal = [[Archives of disease in childhood]]
| volume = 89
| issue = 9
| pages = 809–812
| year = 2004
| month = September
| doi = 10.1136/adc.2003.034587
| pmid = 15321852
}}</ref>
 
=== Surgery ===
* Splenectomy is very effective in reducing hemolysis, leading to significant prolongation of the red cell life span.<ref>{{Cite journal
| author = [[P. H. B. Bolton-Maggs]], [[R. F. Stevens]], [[N. J. Dodd]], [[G. Lamont]], [[P. Tittensor]] & [[M.-J. King]]
| title = Guidelines for the diagnosis and management of hereditary spherocytosis
| journal = [[British journal of haematology]]
| volume = 126
| issue = 4
| pages = 455–474
| year = 2004
| month = August
| doi = 10.1111/j.1365-2141.2004.05052.x
| pmid = 15287938
}}</ref>
* Patients should be selected for splenectomy on the basis of their clinical symptoms and presence of complications such as gallstones, not simply on the basis of diagnosis alone.
* Following splenectomy, the clinical manifestations and complications (anemia & gallstones) are much reduced in severe hereditary spherocytosis and abolished in milder cases, but at the risk of increased life threatening sepsis from encapsulated organisms, particularly streptococcus pneumoniae.<ref name="Bolton-MaggsStevens2004">{{cite journal|last1=Bolton-Maggs|first1=P. H. B.|last2=Stevens|first2=R. F.|last3=Dodd|first3=N. J.|last4=Lamont|first4=G.|last5=Tittensor|first5=P.|last6=King|first6=M.-J.|title=Guidelines for the diagnosis and management of hereditary spherocytosis|journal=British Journal of Haematology|volume=126|issue=4|year=2004|pages=455–474|issn=0007-1048|doi=10.1111/j.1365-2141.2004.05052.x}}</ref>
 
=== 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.
 
==Case Studies==
[[Hereditary spherocytosis case study one|Case #1]]
[[Hereditary spherocytosis case study one|Case #1]]



Latest revision as of 20:28, 10 December 2018

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