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| '''For patient information click [[Hereditary spherocytosis (patient information)|here]]''' | | '''For patient information click [[Hereditary spherocytosis (patient information)|here]]''' |
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| {{CMG}} {{ZAS}} | | {{CMG}}; {{AE}} {{ZAS}} |
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| ==[[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]].
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| == Historical Perspective == | | == [[hereditary spherocytosis historical perspective|Historical Perspective]] == |
| * Hereditary spherocytosis was first described in 1871.<ref>{{Cite journal
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| | author = [[Sayeeda Huq]], [[Mark A. C. Pietroni]], [[Hafizur Rahman]] & [[Mohammad Tariqul Alam]]
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| | title = Hereditary spherocytosis
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| | journal = [[Journal of health, population, and nutrition]]
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| | volume = 28
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| | issue = 1
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| | pages = 107–109
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| | year = 2010
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| | month = February
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| | pmid = 20214092
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| }}</ref>
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| * It is the commonest cause of inherited chronic hemolysis in the northern europe and north america.<ref>{{Cite journal
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| | author = [[Sayeeda Huq]], [[Mark A. C. Pietroni]], [[Hafizur Rahman]] & [[Mohammad Tariqul Alam]]
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| | title = Hereditary spherocytosis
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| | journal = [[Journal of health, population, and nutrition]]
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| | volume = 28
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| | issue = 1
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| | pages = 107–109
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| | year = 2010
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| | month = February
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| | pmid = 20214092
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| }}</ref>
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| == Classification == | | == [[hereditary spherocytosis classification|Classification]] == |
| * Hereditary Spherocytosis classified on basis of underlying defect in protein and also on the basis of severity of hemolysis.
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| * 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=}}
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| {| class="wikitable"
| | == [[hereditary spherocytosis pathophysiology|Pathophysiology]] == |
| |+
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| ! Locus
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| ! Gene
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| ! Protein
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| ! Inheritance
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| ! Severity
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| ! Comment
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| |-
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| | SPH1
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| | ANK1
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| | Ankyrin-1
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| | AD/AR
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| | mild-moderate/moderately severe-severe
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| | often transfusion dependant
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| |-
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| | SPH2
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| | SPTB
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| | Spectrin beta chain,erythrocytic
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| | AD/AR
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| | mild-moderate/severe
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| | 1 fatal infantile case described
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| |-
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| | SPH3
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| | SPTA1
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| | Spectrin alpha chain,erythrocytic1
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| | AR
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| | severe
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| | transfusion dependant
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| |-
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| | SPH4
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| | SLC4A1
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| | Band3(anion transport protein)
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| | AD
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| | mild-moderate
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| | certain SLC4A1 variants cause disease only when biallelic
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| |-
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| | SPH5
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| | EPB42
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| | Protein 4.2
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| | AR
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| | mild-moderate
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| | 1 moderately severe case described
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| |}
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| {| class="wikitable"
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| |+
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| ! Classification
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| ! Mild
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| ! Moderate
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| ! Severe
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| |-
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| ! Hemoglobin (g/dl)
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| | 110-150
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| | 80-120
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| | 60-80
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| |-
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| ! Reticulocyte count (%)
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| | 3-6
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| | >6
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| | >10
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| |-
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| ! Bilirubin (ug/l)
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| | 17-34
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| | >34
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| | >51
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| |-
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| ! Splenectomy
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| | usually not required
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| | indicated during school age, usually before puberty
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| | necessary - delay until 6 years of age if possible
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| |}
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| == 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>
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| * 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).
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| * 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.
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| * The destabilization of membrane leads to both abnormal morphology and reduced red cell life span.
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| * The shorter the life span of red blood cells, the worse the clinical effects.
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| * 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.
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| == 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>
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| * There are 05 genes associated with hereditary spherocytosis including, alpha spectrin (SPTA1), beta spectrin (SPTB), ankyrin (ANK1), band3 (SLC4A1) and protein 4.2 (EPB42).
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| * Mutations in one or more of hereditary spherocytosis related genes can cause membrane protein deficiency leading to hereditary spherocytosis.
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| {| class="wikitable"
| |
| |+Molecular and Genetic Characteristics of 5 Erythrocyte Membrane Protein Genes
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| ! Gene
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| ! Chromosome Location
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| ! Membrane Protein
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| ! Prevalent Mutations
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| ! Heredity
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| ! Associated Disease
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| |-
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| | ANK1
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| |8p11.2
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| | Ankyrin-1
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| | frameshift, nonsense, splicing, novel mutations
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| | autosomal dominant, autosomal recessive
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| | hereditary spherocytosis
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| |-
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| | SLC4A1
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| | 17q21
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| | Band3
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| | missense,frameshift,polymorphism
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| | autosomal dominant
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| | hereditary spherocytosis,distal renal tubular acisosis
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| |-
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| | SPTA1
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| | 1q22-q23
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| | alpha spectrin
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| | SpaLEPRA allele, splicing, frameshift
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| | autosomal recessive
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| | hereditary spherocytosis, hereditary eliptocytosis, hereditary pyropoikilocytosis
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| |-
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| | SPTB
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| | 14q23-q24.1
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| | beta spectrin
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| | splicing, frameshift, nonsense, novel mutations
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| | autosomal dominant
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| | hereditary spherocytosis, hereditary eliptocytosis, hereditary pyropoikilocytosis
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| |-
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| | EBP42
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| | 15q15-q21
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| | protein 4.2
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| | missense, nonsense
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| | autosomal recessive
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| | hereditary spherocytosis
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| |}
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|
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| == 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
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| | author = [[Robert D. Christensen]], [[Hassan M. Yaish]] & [[Patrick G. Gallagher]]
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| | title = A pediatrician's practical guide to diagnosing and treating hereditary spherocytosis in neonates
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| | journal = [[Pediatrics]]
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| | volume = 135
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| | issue = 6
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| | pages = 1107–1114
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| | year = 2015
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| | month = June
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| | doi = 10.1542/peds.2014-3516
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| | pmid = 26009624
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| }}</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>
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| ** Autoimmune hemolysis
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| ** Thermal injury
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| ** Clostridial septicemia
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| ** Wilson disease
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| ** Hemoglobinopathies
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| ** Hereditary stomatocytosis
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| ** Congenital dyserythrpoietic anemia type II
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| == Epidemiology and Demographics == | | == [[hereditary spherocytosis risk factors|Risk Factors]] == |
| * Hereditary spherocytosis is reported worldwide in all racial and ethnic groups.<ref>{{Cite journal
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| | author = [[Silverio Perrotta]], [[Patrick G. Gallagher]] & [[Narla Mohandas]]
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| | title = Hereditary spherocytosis
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| | journal = [[Lancet (London, England)]]
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| | volume = 372
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| | issue = 9647
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| | pages = 1411–1426
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| | year = 2008
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| | month = October
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| | doi = 10.1016/S0140-6736(08)61588-3
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| | pmid = 18940465
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| }}</ref>
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| * It is the most common inherited anemia in the northern European ancestry and north america.<ref>{{Cite journal
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| | author = [[Sayeeda Huq]], [[Mark A. C. Pietroni]], [[Hafizur Rahman]] & [[Mohammad Tariqul Alam]]
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| | title = Hereditary spherocytosis
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| | journal = [[Journal of health, population, and nutrition]]
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| | volume = 28
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| | issue = 1
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| | pages = 107–109
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| | year = 2010
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| | month = February
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| | pmid = 20214092
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| }}</ref>
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| * The reported incidence of hereditary spherocytosis is 1 in 2000 births.<ref>{{Cite journal
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| | author = [[Sayeeda Huq]], [[Mark A. C. Pietroni]], [[Hafizur Rahman]] & [[Mohammad Tariqul Alam]]
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| | title = Hereditary spherocytosis
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| | journal = [[Journal of health, population, and nutrition]]
| |
| | volume = 28
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| | issue = 1
| |
| | pages = 107–109
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| | year = 2010
| |
| | month = February
| |
| | pmid = 20214092
| |
| }}</ref>
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| * 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>
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| == 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
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| | author = [[Sayeeda Huq]], [[Mark A. C. Pietroni]], [[Hafizur Rahman]] & [[Mohammad Tariqul Alam]]
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| | title = Hereditary spherocytosis
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| | journal = [[Journal of health, population, and nutrition]]
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| | volume = 28
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| | issue = 1
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| | pages = 107–109
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| | year = 2010
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| | month = February
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| | pmid = 20214092
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| }}</ref>
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| * There are no other risk factors have been clearly identified for this condition.
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| == 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
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| | author = [[L. A. Michaels]], [[A. R. Cohen]], [[H. Zhao]], [[R. I. Raphael]] & [[C. S. Manno]]
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| | title = Screening for hereditary spherocytosis by use of automated erythrocyte indexes
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| | journal = [[The Journal of pediatrics]]
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| | volume = 130
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| | issue = 6
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| | pages = 957–960
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| | year = 1997
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| | month = June
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| | pmid = 9202619
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| }}</ref>
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| * Erythrocyte distribution width when raised is also useful as a powerful screening test.<ref>{{Cite journal
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| | author = [[Silvia Eandi Eberle]], [[Gabriela Sciuccati]], [[Mariana Bonduel]], [[Lilian Diaz]], [[Raquel Staciuk]] & [[Aurora Feliu Torres]]
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| | title = [Erythrocyte indexes in hereditary spherocytosis]
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| | journal = [[Medicina]]
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| | volume = 67
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| | issue = 6 Pt 2
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| | pages = 698–700
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| | year = 2007
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| | month =
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| | pmid = 18422060
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| }}</ref>
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| * 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>
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| == Natural History, Complications, and Prognosis == | | == [[hereditary spherocytosis diagnostic study of choice|Diagnosis]] == |
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| === 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
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| | author = [[Olga Ciepiela]]
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| | title = Old and new insights into the diagnosis of hereditary spherocytosis
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| | journal = [[Annals of translational medicine]]
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| | volume = 6
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| | issue = 17
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| | pages = 339
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| | year = 2018
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| | month = September
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| | doi = 10.21037/atm.2018.07.35
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| | pmid = 30306078
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| }}</ref>
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| * 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
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| | author = [[F. Delhommeau]], [[T. Cynober]], [[P. O. Schischmanoff]], [[P. Rohrlich]], [[J. Delaunay]], [[N. Mohandas]] & [[G. Tchernia]]
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| | title = Natural history of hereditary spherocytosis during the first year of life
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| | journal = [[Blood]]
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| | volume = 95
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| | issue = 2
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| | pages = 393–397
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| | year = 2000
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| | month = January
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| | pmid = 10627440
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| }}</ref>
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| * About 20-30% of patients have mild disease with compensated hemolysis.
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| * About 60-70% of patients have moderate disease, presenting in childhood but can present at any age.
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| * 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.
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| * 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>
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| === Complications === | | == [[hereditary spherocytosis physical examination|Physical Examination]] == |
| * The complications of hereditary spherocytosis include:<ref>{{Cite journal
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| | author = [[Sayeeda Huq]], [[Mark A. C. Pietroni]], [[Hafizur Rahman]] & [[Mohammad Tariqul Alam]]
| |
| | title = Hereditary spherocytosis
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| | journal = [[Journal of health, population, and nutrition]]
| |
| | volume = 28
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| | 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>
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| ** hemolytic anemia
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| ** jaundice
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| ** kernicterus
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| ** cholelithiasis
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| ** hemolytic, aplastic and megaloblastic crises
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| ** growth failure
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| ** leg ulcers
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| ** skeletal abnormalities resulting from bone marrow expansion
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| ** multiple myeloma
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| ** leukemia
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|
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| === 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
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| | author = [[Yuki Tateno]], [[Ryoji Suzuki]] & [[Yukihiro Kitamura]]
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| | title = Previously undiagnosed hereditary spherocytosis in a patient with jaundice and pyelonephritis: a case report
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| | journal = [[Journal of medical case reports]]
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| | volume = 10
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| | issue = 1
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| | pages = 337
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| | year = 2016
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| | month = December
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| | doi = 10.1186/s13256-016-1144-8
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| | pmid = 27906107
| |
| }}</ref>
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| * Patients with hereditary spherocytosis may remain undiagnosed for years if their hemolysis is mild.
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|
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| == Diagnosis == | | == [[hereditary spherocytosis chest x ray|Chest X ray]] == |
|
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| === 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>
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| * The diagnosis can be made at any age, including the neonatal period from day of birth.
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| * 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.
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| * 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)
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| * 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
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| | author = [[Immacolata Andolfo]], [[Roberta Russo]], [[Antonella Gambale]] & [[Achille Iolascon]]
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| | title = New insights on hereditary erythrocyte membrane defects
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| | journal = [[Haematologica]]
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| | volume = 101
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| | issue = 11
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| | pages = 1284–1294
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| | year = 2016
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| | month = November
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| | doi = 10.3324/haematol.2016.142463
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| | pmid = 27756835
| |
| }}</ref>
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| * Ektacytometry is a highly sensitive test of membrane deformability.
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|
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|
| | == [[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
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| | pallor, splenomegaly, inconstant jaundice
| |
| |-
| |
| ! Biological paraneters & erythrocyte indices
| |
| | dec Hb, inc MCHC, inc %hyperdense cells, inc reticulocytes
| |
| |-
| |
| ! Blood smear
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| | Spherocytes (may be absent)
| |
| |-
| |
| ! Signs of hemolysis
| |
| | inc free bilirubin, dec haptoglobin, inc reticulocytes
| |
| |-
| |
| ! Erythrocyte coombs test
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| | negative
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| |}
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|
| |
|
| {| class="wikitable"
| | == [[hereditary spherocytosis other diagnostic studies|Other Diagnostic Studies]] == |
| |+
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| Specific Biological Examinations for the Diagnosis of Hereditary Spherocytosis
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| ! Tests
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| ! Principle/feasibility
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| ! Sensitivity/Specificity
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| |-
| |
| | Osmotic resistance
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| | hemolysis test/routime examination
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| | 66%/low
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| |-
| |
| | Pink test
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| | hemolysis test/simple test time-out test <3 hours
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| | 96%/79-94%
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| |-
| |
| | AGLT
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| | Hemolysis test time of test >3 hours
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| | 81%/95%
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| |-
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| | Ektacytometry in osmolar gradient
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| | study of deformity of RBCs single laboratory in France test execution time:24 hours
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| | reference exam
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| |-
| |
| | Flow cytometry
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| | labeling of RBCs with eosin 5 maleimide/not available on routine basis test run time >48 h
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| | Being evaluated
| |
| |}
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|
| |
|
| === History and Symptoms === | | == [[hereditary spherocytosis medical therapy|Treatment]] == |
| * 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:
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| ** Yellowing of the skin and eyes (jaundice)
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| ** [[Pallor|Pale coloring (pallor)]]
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| ** [[Fatigue]]
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| ** Irritability
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| ** [[Shortness of breath]]
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| ** [[Weakness]]
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|
| |
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| === Physical Examination === | | == [[hereditary spherocytosis medical therapy|Medical Therapy]] == |
| * [[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.
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|
| |
|
| * 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|gallbladder disease.]]
| | == [[hereditary spherocytosis surgery|Surgery]] == |
| * 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.
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|
| |
|
| === Laboratory Findings === | | ==[[hereditary spherocytosis primary prevention|Primary Prevention]] == |
| '''Initial testing'''
| |
| *<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]].
| |
| * '''[[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'''
| |
| * '''EMA binding''' ●'''Osmotic fragility''' '''●Glycerol lysis''' ●'''Cryohemolysis'''
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|
| |
|
| === Imaging Findings: === | | == [[hereditary spherocytosis secondary prevention|Secondary Prevention]]== |
| * There are no particular other imaging findings associated with HS.
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|
| |
|
| === Other Diagnostic Studies: === | | == [[hereditary spherocytosis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] == |
| ** In certain atypical cases in which further characterization of the RBC cytoskeletal/membrane proteins is needed, gel electrophoresis can be done using RBC ghosts, or DNA sequencing can be performed.
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|
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|
| == Treatment == | | == [[hereditary spherocytosis future or investigational therapies|Future or Investigational Therapies]] == |
|
| |
|
| === Medical Therapy === | | == [[Hereditary spherocytosis case study one|Case Studies]] == |
| * 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.
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| | |
| ==Case Studies==
| |
| [[Hereditary spherocytosis case study one|Case #1]] | | [[Hereditary spherocytosis case study one|Case #1]] |
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