Stomatocytes are erythrocytes with an elongated (mouth-like) area of central pallor.

An occasional cell of this type might be seen as a non-specific finding in a variety of situations, such as regenerative anemias, liver disease, and lead poisoning. Stomatocytes can also be an artifact in a blood smear that is too thick. Hereditary stomatocytosis occurs in some Alaskan alamute dogs in association with chondrodysplasia which manifests as dwarfism. !t is inherited as an autosomal recessive 7umerous stomatocytes in the blood of ain homo"ygous trait. !n addition to the morphologic abnormality, the red cell population chondrodysplastic Alaskan malamute affected dogs is macrocytic (up to #$ f%), and hypochromic (&'-&$().dog. )rythrocyte numbers are lower than normal, but, due to the larger cell si"e, hematocrits are within reference intervals. *ed blood cell lifespan is reduced, with e+travascular hemolysis and a mild reticulocytosis, and the cells are osmotically and mechanically fragile. ,he precise defect is unknown, but it is a membrane defect involving increased sodium and water influ+. Hereditary stomatocytosis has also been reported in -rentse patri.shond (in con.uction with hypertrophic gastritis) and iniature Schnau"ers (autosomal recessive). /e have seen one case of stomatocytosis in a 0eek-a-poo at 1ornell 2niversity. !n the -rentse patri.shond, dogs are anemic (Hct, 3$-4$() with reticulocytosis (&.5-3&(), macrocytic (6&-$3 f%) and hypochromic. Stomatocytes are seen in 35-4$( of red blood cells by light microscopy. ,he defect is due to abnormal phospholipid composition in the red blood cell membrane (increased sphingomyelin and decreased cholesterol and phosphatidylcholine, with the latter being the most consistent change). ,he dogs usually die of hemolytic anemia.
http://diaglab.vet.cornell.edu/clinpath/modules/rbcmorph/stomato.htm

Stomatocytes are red blood cells with an oval or rectangular area of central pallor, sometimes referred to as a "mouth". These cells have lost the indentation on one side and may be found in liver disease, electrolyte imbalance, and hereditary stomatocytosis.

http://emedicine.medscape.com/article/955921-overview

Introduction
Background
Abnormalities of red cell membrane cation permeability are seen in several hereditary disorders. These dominantly inherited conditions are collectively called the hereditary stomatocytoses and allied disorders. This class of hemolytic anemias is clinically diverse.1 Overhydrated hereditary stomatocytosis (OHS), also called hydrocytosis, was the first of these disorders to be described.2 An abnormally increased cation infl ! res lts in swollen erythrocytes, hemolysis, and stomatocytes. At the other end of the spectr m, net loss of cations and water res lts in dehydrated hereditary stomatocytosis ("HS), which is also called !erocytosis. #ntermediate syndromes that are asymptomatic or have mi!ed feat res, s ch as cryohydrocytosis ($H$) and familial pse dohyper%alemia (&'), have also been described.

$H$ has been lin%ed to m tations in the band ( chloride)bicarbonate e!chan*er A+1.( "HS and most cases of &' have been mapped to the 1,-2()2. *enetic loc s.. OHS has not yet been lin%ed to an nderlyin* *ene m tation, and the observed decrease in stomatin, or protein /.2b, is tho *ht to be a traffic%in* alteration.0

Pathophysiology
+rythrocytes have intracell lar hemo*lobin, 2)(,diphospho*lycerate (2,()"'1), and AT', which all e!ert osmotic press re across the semipermeable cell membrane. 2y transportin* 3a4 and 54 ions across the cell membrane, red cells can ad6 st the intracell lar concentration of these cations and re* late intracell lar hydration. Any dist rbances in membrane cation permeability alter cell lar hydration and can ca se n mero s effects, incl din* hemolysis. #n OHS, the ma6or defect is a mar%ed asymmetric increase in passive 3a 4 and 54 permeability. The infl ! of 3a4e!ceeds the loss of 54, ca sin* a net infl ! of water, overhydration, and swellin*. The res ltin* hydrocytosis leads to increased osmotic fra*ility and decreased deformability, with conse- ent hemolysis. The nderlyin* *ene m tation is n%nown, and the observed decrease in stomatin, or protein /.2b, is tho *ht to be a traffic%in* alteration.0 #n contrast, the primary abnormality in "HS is a chan*e in the relative membrane permeability to 54. +ffl ! of 54 is increased 2)fold to .)fold and res lts in cation depletion, with decreased intracell lar osmolality and water loss. The !erocytes formed are shear)sensitive and prone to membrane fra*mentation in response to metabolic stress, with s bse- ent hemolysis. &' is s ally asymptomatic or rarely shows mild macrocytosis. 7hen erythrocytes are cooled to room temperat re or lower (e*, after phlebotomy), the net 54 lea% is *reater than e!pected and res lts in factitio s hyper%alemia., "HS and most cases of &' have been mapped to the 1,-2()2. *enetic loc s.. $H$ clinically manifests with mild hemolytic anemia and is remar%able for an abnormality of the band ( chloride)bicarbonate e!chan*er A+1. ( At low temperat res, the defective anion channel appears to allow a si*nificant cation lea%, and a tohemolysis may be seen in vitro at .o $. The molec lar defects that transform A+1 into a cation channel are c rrently nder investi*ation./

Frequency
International

These hereditary syndromes are e!tremely rare, and acc rate data concernin* their prevalence are lac%in*. "HS occ rs in 1 per 08,888 live births. 9 "HS %indreds in #reland: and &rance18 have been reported.

Mortality/Morbidity
;orbidity in these disorders depends on the severity of the hemolytic anemia. The

ris%s for neonatal hyperbilir binemia with %ernicter s are similar to those of other hemolytic anemias. +!chan*e transf sion is occasionally re- ired. Aplastic crises associated with parvovir s infection occ r, altho *h they are infre- ent. 2oth OHS and "HS are associated with a si*nificant ris% of serio s thrombosis after splenectomy, altho *h the reason for this is n%nown. ;ost patients with OHS have chronic low)*rade anemia p nct ated by rec rrent episodes of more severe anemia and 6a ndice. Other patients have a m ch milder disease. #ron overload, re*ardless of transf sion stat s, is now well reco*ni<ed. ;ost patients with "HS are asymptomatic b t e!perience mild)to)moderate hemolytic anemia, which is *enerally well compensated. Hydrops fetalis and neonatal ascites have been reported in a few %indreds.11 +!chan*e transf sions are occasionally re- ired. +ven simple transf sions carry ris%s of infection, aller*ic reactions, and febrile or hemolytic transf sion reactions.

Race
;ost patients with hereditary disorders of red cell permeability are white people of + ropean descent.

Sex
These syndromes have no %nown se! predilection, and clinical manifestations are not affected by se!.

Clinical
History
The hereditary stomatocytosis syndromes and allied disorders are s ally transmitted in an a tosomal dominant pattern, altho *h apparently sporadic cases have been reported. 'enetrance varies, with si*nificant disparity in clinical symptomatolo*y between affected individ als in the same %indred. ;any patients present with hemolytic anemia in the neonatal period, b t others are asymptomatic thro *ho t their lifetime. Aplastic crises associated with parvovir s and other infections have been reported. An n s al characteristic of the stomatocytosis syndromes is a predisposition to severe life)threatenin* thrombosis after splenectomy. A n mber of ac- ired conditions are associated with stomatocytes in the blood, altho *h patients with these conditions rarely present with hematolo*ic manifestations. #n addition, stomatocytosis may be observed in the conte!t of inherited conditions s ch as ;editerranean stomatocytosis, which does not affect erythrocyte permeability and has an accompanyin* thrombocytopenia. Overhydrated hereditary stomatocytosis (OHS) o The de*ree of hemolysis and anemia varies.

o o

;oderate)to)severe lifelon* hemolytic anemia is most typical. A few reports described patients who e!perienced symptoms of vaso)occl sion, s ch as dyspnea, chest pain, and abdominal pain, partic larly after splenectomy. Anemia is *enerally not present at birth, b t neonatal 6a ndice is relatively common and is occasionally serio s eno *h to warrant e!chan*e transf sion. 'atients with severe disease are s ally yo n*er than , months at presentation.

"ehydrated hereditary stomatocytosis ("HS) o This is the most common form of the hereditary stomatocytosis syndromes. 'atients typically present with compensated mild)to)moderate hemolytic anemia. 'eriodic episodes of 6a ndice are common. ;ost patients are asymptomatic, altho *h easy fati*ability is a common symptom. A few case reports have doc mented "HS in association with rec rrent fetal loss or with hydrops fetalis. The presence of perinatal eff sions may re- ire ascitic taps b t is not a predictor of the severity of anemia later in life.12 The mechanism for this is ncertain b t may involve hepatic dysf nction.1( #ron overload is common, and ad lts may be dia*nosed with hemochromatosis. The mechanism for this is n%nown.1.

#ntermediate syndromes o 'atients with intermediate syndromes do not have consistent hemolytic anemia. $ryohydrocytosis ($H$) is an intermediate syndrome in which erythrocytes nder*o spontaneo s in vitro hemolysis after stora*e at .=$. &amilial pse dohyper%alemia (&') s ally manifests with factitio s hyper%alemia. >ed cell macrocytosis is rare.

Physical
&oc s the physical e!amination on or*an systems affected by hemolytic anemia. 'allor, 6a ndice, hepatosplenome*aly, and si*ns of *allstone disease are the most li%ely physical findin*s. +val ate si*ns of cardiovasc lar compromise in patients who are ill.

;onitor *rowth parameters yearly in children. ;onitor ferritin levels for iron overload.

Causes
As described above, the hereditary stomatocytosis disorders and allied syndromes are all inherited in an a tosomal dominant fashion. "HS and some cases of &' map to chromosome band 1,-2()2.. $H$ is associated with m tations of band ( (A+1). 3o nderlyin* m tation has been identified in OHS.