Haematologists have identified a number of variants. These can be classified as below.

- Overhydrated hereditary stomatocytosis

- Dehydrated HSt (hereditary xerocytosis; hereditary hyperphosphatidylcholine haemolytic anaemia)

- Dehydrated with perinatal ascites

- Cryohydrocytosis

- 'Blackburn' variant.

- Familial pseudohyperkalaemia

There are other families that do not fall neatly into any of these classifications.

Stomatocytosis is also found as a hereditary disease in Alaskan malamute and miniature schnauzer dogs.

Hereditary stomatocytosis describes a number of inherited autosomal dominant human conditions which affect the red blood cell, in which the membrane or outer coating of the cell 'leaks' sodium and potassium ions.

HPFH may alleviate the severity of certain hemoglobinopathies and thalassemias, and is selected for in populations with a high prevalence of these conditions (which in turn are often selected for in areas where malaria is endemic). Thus, it has been found to affect Americans of African and Greek descent.

Genetic testing for the presence of mutations in protein molecules is considered to be a confirmatory testing technique. It is important to know the risks regarding the transmission and dangers of HPP.

Those with hereditary elliptocytosis have a good prognosis, only those with very severe disease have a shortened life expectancy.

Hereditary spherocytosis is the most common disorder of the red cell membrane and affects 1 in 2,000 people of Northern European ancestry. According to Harrison's Principles of Internal Medicine, the frequency is at least 1 in 5,000.

This is usually caused by mutations in the "β or α" globin gene cluster, or the γ promoter gene region. . The percentage of incorrect expression might be as low as 10-15% or as high as 100% of the total hemoglobin, usually higher in homozygotes than in heterozygotes.

Congenital dyserythropoietic anemia type II (CDA II), or hereditary erythroblastic multinuclearity with positive acidified serum lysis test (HEMPAS) is a rare genetic anemia in humans characterized by hereditary erythroblastic multinuclearity with positive acidified serum lysis test.

Hereditary pyropoikilocytosis (HPP) is an autosomal recessive form of hemolytic anemia characterized by an abnormal sensitivity of red blood cells to heat and erythrocyte morphology similar to that seen in thermal burns. Patients with HPP tend to experience severe haemolysis and anaemia in infancy that gradually improves, evolving toward typical elliptocytosis later in life. However, the hemolysis can lead to rapid sequestration and destruction of red cells. Splenectomy is curative when this occurs.

HPP has been associated with a defect of the erythrocyte membrane protein spectrin and with spectrin deficiency.It was characterized in 1975.It is considered a severe form of hereditary elliptocytosis.

Experimental gene therapy exists to treat hereditary spherocytosis in lab mice; however, this treatment has not yet been tried on humans due to all of the risks involved in human gene therapy.

The anemia associated with CDA type II can range from mild to severe, and most affected individuals have jaundice, hepatosplenomegaly, and the formation of hard deposits in the gallbladder called bilirubin gallstones. This form of the disorder is usually diagnosed in adolescence or early adulthood. An abnormal buildup of iron typically occurs after age 20, leading to complications including heart disease, diabetes, and cirrhosis.

The incidence of hereditary elliptocytosis is hard to determine, as many sufferers of the milder forms of the disorder are asymptomatic and their condition never comes to medical attention. Around 90% of those with this disorder are thought to fall into the asymptomatic population. It is estimated that its incidence is between 3 and 5 per 10,000 in the United States, and that those of African and Mediterranean descent are of higher risk. Because it can confer resistance to malaria, some subtypes of hereditary elliptocytosis are significantly more prevalent in regions where malaria is endemic. For example, in equatorial Africa its incidence is estimated at 60-160 per 10,000, and in Malayan natives its incidence is 1500-2000 per 10,000. Almost all forms of hereditary elliptocytosis are autosomal dominant, and both sexes are therefore at equal risk of having the condition. The most important exception to this rule of autosomal dominance is for a subtype of hereditary elliptocytosis called hereditary pyropoikilocytosis (HPP), which is autosomal recessive.

There are three major forms of hereditary elliptocytosis: common hereditary elliptocytosis, spherocytic elliptocytosis and southeast Asian ovalocytosis.

Common hereditary elliptocytosis is the most common form of elliptocytosis, and the form most extensively researched. Even when looking only at this form of elliptocytosis, there is a high degree of variability in the clinical severity of its subtypes. A clinically significant haemolytic anaemia occurs only in 5-10% of sufferers, with a strong bias towards those with more severe subtypes of the disorder.

Southeast Asian ovalocytosis and spherocytic elliptocytosis are less common subtypes predominantly affecting those of south-east Asian and European ethnic groups, respectively.

The following categorisation of the disorder demonstrates its heterogeneity:

- Common hereditary elliptocytosis (in approximate order from least severe to most severe)

- With asymptomatic carrier status - "individuals have no symptoms of disease and diagnosis is only able to be made on blood film"

- With mild disease - "individuals have no symptoms, with a mild and compensated haemolytic anaemia"

- With sporadic haemolysis - "individuals are at risk of haemolysis in the presence of particular comorbidities, including infections, and vitamin B deficiency"

- With neonatal poikilocytosis - "individuals have a symptomatic haemolytic anaemia with poikilocytosis that resolves in the first year of life"

- With chronic haemolysis - " individual has a moderate to severe symptomatic haemolytic anaemia (this subtype has variable penetrance in some pedigrees)"

- With homozygosity or compound heterozygosity - "depending on the exact mutations involved, individuals may lie anywhere in the spectrum between having a mild haemolytic anaemia and having a life-threatening haemolytic anaemia with symptoms mimicking those of HPP (see below)"

- With pyropoikilocytosis (HPP) - "individuals are typically of African descent and have a life-threateningly severe haemolytic anaemia with micropoikilocytosis (small and misshapen erythrocytes) that is compounded by a marked instability of erythrocytes in even mildly elevated temperatures (pyropoikilocytosis is often found in burns victims and is the term is commonly used in reference to such people)

- South-east Asian ovalocytosis (SAO) (also called stomatocytic elliptocytosis) - "individuals are of South-East Asian descent (typically Malaysian, Indonesian, Melanesian, New Guinean or Filipino, have a mild haemolytic anaemia, and has increased resistance to malaria"

- Spherocytic elliptocytosis (also called hereditary haemolytic ovalocytosis) - "individuals are of European descent and elliptocytes and spherocytes are simultaneously present in their blood"

Harderoporphyria is a rare disorder of heme biosynthesis, inherited in an autosomal recessive manner caused by specific mutations in the "CPOX" gene. Mutations in "CPOX" usually cause hereditary coproporphyria, an acute hepatic porphyria, however the K404E mutation in a homozygous or compound heterozygous state with a null allele cause the more severe harderoporphyria. Harderoporphyria is the first known metabolic disorder where the disease phenotype depended on the type and location of the mutations in a gene associated with multiple disorders.

In contrast with other porphyrias, which typically present with either cutaneous lesions after exposure to sunlight or acute neurovisceral attack at any age (most commonly in adulthood), harderoporphyria is characterized by jaundice, anemia enlarged liver and spleen, often presenting in the neonatal period. Later in life, these individuals may present with photosensitivity similar to that found in cutaneous porphyrias.

Biochemically, harderoporphyria presents with a distinct pattern of increased harderoporphyrin (2-vinyl-4,6,7-tripropionic acid porphyrin) in urine and particularly in feces, a metabolite that is not seen in significant quantities in any other porphyria. Enzyme tests show markedly reduced activity of coproporphyrinogen oxidase, compared to both unaffected individuals and those affected with hereditary coproporphyria, consistent with recessive inheritance.

Harderoporphyria is a rare condition, with less than 10 cases reported worldwide. It may be underdiagnosed, as it does not have the typical presentation associated with a porphyria. It was identified as a variant type of coproporphyria in 1983, in a family with three children identified at birth with jaundice and hemolytic anemia. There is no standard treatment for harderoporphyria; care is mainly focused on the management of symptoms.

Southeast Asian ovalocytosis is a blood disorder that is similar to, but distinct from hereditary elliptocytosis. It is common in some communities in Malaysia and Papua New Guinea, as it confers some resistance to cerebral Falciparum Malaria.

Affected individuals over age 40 or who have high serum ferritin levels are at risk for developing cirrhosis. Iron overload increases the risk of hepatocellular carcinoma. This risk is greater in those with cirrhosis but is still present in those without cirrhosis. Significant problems occur in around one in ten.

It is most common in certain European populations (such as the Irish and Norwegians) and occurs in 0.6% of the population. Men with the disease are 24 times more likely to experience symptoms than affected women.

Studies indicate that persons with symptomatic haemochromatosis have somewhat reduced life expectancy compared to the general population. This is mainly due to excess mortality from cirrhosis and liver cancer. Patients who were treated with phlebotomy lived longer than those who weren't. Patients without liver disease or diabetes had similar survival rate to the general population.

Asplenia is the absence of normal spleen function. It predisposes to some septicemia infections. Therefore, vaccination and antibiotic measures are essential in such cases. There are multiple causes:

- Some people congenitally completely lack a spleen, although this is rare.

- Sickle-cell disease can cause a functional asplenia (or autosplenectomy) by causing infarctions of the spleen during repeated sickle-cell crises.

- It may be removed surgically (known as a splenectomy), but this is rarely performed, as it carries a high risk of infection and other adverse effects. Indications include following abdominal injuries with rupture and hemorrhage of the spleen, or in the treatment of certain blood diseases (Idiopathic thrombocytopenic purpura, hereditary spherocytosis, etc.), certain forms of lymphoma or for the removal of splenic tumors or cysts.

The condition is sometimes confused with juvenile hemochromatosis, which is a hereditary hemochromatosis caused by mutations of a gene called hemojuvelin. While the symptoms and outcomes for these two diseases are similar, the causes appear to be different.

The causes of neonatal hemochromatosis are still unknown, but recent research has led to the hypothesis that it is an alloimmune disease. Evidence supporting this hypothesis includes the high rate among siblings (>80%). This evidence along with other research indicates that neonatal hemochromatosis could be classified as a congenital alloimmune hepatitis.

The issue is thought of as representing any of the following:

- a decreased production of normal-sized red blood cells (e.g., anemia of chronic disease, aplastic anemia);

- an increased production of HbS as seen in sickle cell disease (not sickle cell trait);

- an increased destruction or loss of red blood cells (e.g., hemolysis, posthemorrhagic anemia);

- an uncompensated increase in plasma volume (e.g., pregnancy, fluid overload);

- a B2 (riboflavin) deficiency

- a B6 (pyridoxine) deficiency

- or a mixture of conditions producing microcytic and macrocytic anemia.

Blood loss, suppressed production of RBCs or hemolysis represent most cases of normocytic anemia. In blood loss, morphologic findings are generally unremarkable except after 12 to 24 hrs where polychromasia appears. For reduced production of RBCs, like with low erythropoietin, the RBC morphology is unremarkable. Patients with disordered RBC production, e.g. myelodysplastic syndrome, may have a dual population of elliptocytes, teardrop cells, or other poikilocytes as well as a nucleated RBCs. Hemolysis will often demonstrate poikilocytes specific to a cause or mechanism. E.g. Bite cells and/or blistor cells for oxidative hemolysis, Acanthocytes for pyruvate kinase deficiency or McLeod phenotype, Sickle cells for sickle cell anemia, Spherocytes for immune-mediated hemolysis or hereditary spherocytosis, Elliptocytosis for iron deficiency or hereditary elliptocytosis and schistocytes for intravascular hemolysis. Many hemolytic anemias show multiple poikilocytes such as G6PD deficiency which may show blister and bites cells as well as shistocytes. Neonatal hemolysis may not follow the classic patterns as in adults

It is hereditary haemolytic anaemia in which the red blood cell is oval-shaped. The primary defect in SAO differs significantly from other forms of elliptocytosis in that it is a defect in the gene coding for a protein that is not directly involved in the cytoskeleton scaffolding of the cell. Rather, the defect lies in a protein known as the band 3 protein, which lies in the cell membrane itself. The band 3 protein normally binds to another membrane-bound protein called ankyrin, but in SAO this bond is stronger than normal. Other abnormalities include tighter tethering of the band 3 protein to the cell membrane, increased tyrosine phosphorylation of the band 3 protein, reduced sulfate anion transport through the cell membrane, and more rapid ATP consumption. These (and probably other) consequences of the SAO mutations lead to the following erythrocyte abnormalities:

- A greater robustness of cells to a variety of external forces, including:

- Reduction in cellular sensitivity to osmotic pressures

- Reduction in fragility related to temperature change

- greater general rigidity of the cell membrane

- Loss of sensitivity to substances that cause of cells

- Reduced anion exchange

- Partial intracellular depletion of ATP

- A reduction in expression of multiple antigens

These changes are thought to give rise to the scientifically and clinically interesting phenomenon that those with SAO exhibit: a marked "in vivo" resistance to infection by the causative pathogen of malaria, "Plasmodium falciparum". Unlike those with the Leach phenotype of common hereditary elliptocytosis (see above), there is a clinically significant reduction in both disease severity and prevalence of malaria in those with SAO. Because of this, the 35% incidence rate of SAO along the north coast of Madang Province in Papua New Guinea, where malaria in endemic, is a good example of natural selection.

The reasons behind the resistance to malaria become clear when given an explanation the way in which "Plasmodium falciparum" invades its host. This parasite is an obligate intracellular parasite, which must enter the cells of the host it is invading. The band 3 proteins aggregate on the cell membrane at the site of entry, forming a circular that the parasite squeezes through. These band 3 proteins act as receptors for the parasite. Normally a process much like endocytosis occurs, and the parasite is able to isolate itself from the intracellular proteins that are toxic to it while still being inside an erythrocyte (see figure 2). The increased rigidity of the erythrocyte membrane in SAO is thought to reduce the capacity of the band 3 proteins to cluster together, thereby making it more difficult for the malaria parasite to properly attaching to and enter the cell. The reduced free ATP within the cell has been postulated as a further mechanism behind which SAO creates a hostile environment for "Plasmodium falciparum".

Certain mutations in the fibrinogen Aα-chain gene cause a form of familial renal amyloidosis termed hereditary fibrinogen Aα-Chain amyloidosis. The disorder is due to autosomal dominant inheritance of Aα chain mutations the most common of which is hemoglobin Indianopolis, a heterzyogus missense (c.1718G>T: Arg554Leu) mutation. Other missense mutations causing this disorder are unnamed; they include 1634A>T: Glu526Val; c.1670C>A: Thr538lys; c.1676A.T:Glu540Val; and c1712C>A:Pro552Hi. A deletion mutation causing a frameshift viz., c.1622delT: Thr525Leufs, is also a cause of the disorder. The fibrinogen bearing these mutant Aα-chains is secreted into the circulation and gradually accumulates in, and causes significant injury to, the kidney. The mutant fibrinogen does not appear to accumulate in, or injure, extra-renal tissues.

Spherocytosis is an auto-hemolytic anemia (a disease of the blood) characterized by the production of spherocytes (red blood cells (RBCs)) or erythrocytes that are sphere-shaped rather than bi-concave disk shaped. Spherocytes are found in all hemolytic anemias to some degree. Hereditary spherocytosis and autoimmune hemolytic anemia are characterized by having "only" spherocytes.

Spherocytosis most often refers to hereditary spherocytosis. This is caused by a molecular defect in one or more of the proteins of the red blood cell cytoskeleton, including spectrin, ankyrin, Band 3, or Protein 4.2. Because the cell skeleton has a defect, the blood cell contracts to a sphere, which is its most surface tension efficient and least flexible configuration. Though the spherocytes have a smaller surface area through which oxygen and carbon dioxide can be exchanged, they in themselves perform adequately to maintain healthy oxygen supplies. However, they have a high osmotic fragility—when placed into water, they are more likely to burst than normal red blood cells. These cells are more prone to physical degradation.

Spherocytes are most commonly found in immunologically-mediated hemolytic anemias and in hereditary spherocytosis, but the former would have a positive direct Coombs test and the latter would not. The misshapen but otherwise healthy red blood cells are mistaken by the spleen for old or damaged red blood cells and it thus constantly breaks them down, causing a cycle whereby the body destroys its own blood supply (auto-hemolysis). A complete blood count (CBC) may show increased reticulocytes, a sign of increased red blood cell production, and decreased hemoglobin and hematocrit.

The term "non-hereditary spherocytosis" is occasionally used, albeit rarely.

Individuals experiencing episodic bleeding as a result of congenital dysfibrinogenemia should be treated at a center specialized in treating hemophilia. They should avoid all medications that interfere with normal platelet function. During bleeding episodes, treatment with fibrinogen concentrates or in emergencies or when these concentrates are unavailable, infusions of fresh frozen plasma and/or cryoprecipitate (a fibrinogen-rich plasma fraction) to maintain fibrinogen activity levels >1 gram/liter. Tranexamic acid or fibrinogen concentrates are recommended for prophylactic treatment prior to minor surgery while fibrinogen concentrates are recommended prior to major surgery with fibrinogen concentrates usage seeking to maintain fibrinogen activity levels at >1 gram/liter. Women undergoing vaginal or Cesarean child birth should be treated at a hemophilia center with fibrinogen concentrates to maintain fibrinogen activity levels at 1.5 gram/liter. The latter individuals require careful observation for bleeding during their post-partum periods.

Individuals experiencing episodic thrombosis as a result of congenital dysfibrinogenemia should also be treated at a center specialized in treating hemophilia using antithrombotic agents. They should be instructed on antithrombotic behavioral methods fur use in high risk situations such as long car rides and air flights. Venous thrombosis should be treated with low molecular weight heparin for a period that depends on personal and family history of thrombosis events. Prophylactic treatment prior to minor surgery should avoid fibrinogen supplementation and use prophylactic anticoagulation measures; prior to major surgery, fibrinogen supplementation should be used only if serious bleeding occurs; otherwise, prophylactic anticoagulation measures are recommended.