Acute renal failure occurs in 55–70% of patients with STEC-HUS, although up to 70–85% recover renal function. Patients with aHUS generally have poor outcomes, with up to 50% progressing to ESRD or irreversible brain damage; as many as 25% die during the acute phase. However, with aggressive treatment, more than 90% of patients survive the acute phase of HUS, and only about 9% may develop ESRD. Roughly one-third of persons with HUS have abnormal kidney function many years later, and a few require long-term dialysis. Another 8% of persons with HUS have other lifelong complications, such as high blood pressure, seizures, blindness, paralysis, and the effects of having part of their colon removed. The overall mortality rate from HUS is 5–15%. Children and the elderly have a worse prognosis.

Atypical HUS (aHUS) represents 5–10% of HUS cases and is largely due to one or several genetic mutations that cause chronic, uncontrolled, and excessive activation of complement. This results in platelet activation endothelial cell damage, and white blood cell activation, leading to systemic TMA, which manifests as decreased platelet count, hemolysis (breakdown of red blood cells), damage to multiple organs, and ultimately death. Early signs of systemic complement-mediated TMA include thrombocytopenia (platelet count below 150,000 or a decrease from baseline of at least 25%) and evidence of microangiopathic hemolysis, which is characterized by elevated LDH levels, decreased haptoglobin, decreased hemoglobin (the oxygen-containing component of blood), and/or the presence of schistocytes. Despite the use of supportive care, an estimated 33–40% of patients will die or have end-stage renal disease (ESRD) with the first clinical manifestation of aHUS, and 65% of patients will die, require dialysis, or have permanent renal damage within the first year after diagnosis despite plasma exchange or plasma infusion (PE/PI) therapy. Patients who survive the presenting signs and symptoms of aHUS endure a chronic thrombotic and inflammatory state, which puts them at lifelong elevated risk of sudden blood clotting, kidney failure, other severe complications and premature death.

Historically, treatment options for aHUS were limited to plasma exchange or plasma infusion (PE/PI) therapy, which carries significant safety risks and has not been proven effective in any controlled clinical trials. Patients with aHUS and ESRD have also had to undergo lifelong dialysis, which has a 5-year survival rate of 34–38%. In recent years the monoclonal antibody eculizumab (INN and USAN, trade name Soliris), a first-in-class terminal complement inhibitor, has been shown in clinical studies to block terminal complement activity in children and adults with aHUS, and to eliminate the need for PE/PI and new dialysis. In these studies eculizumab was associated with reduced TMA activity, as shown by improvement in platelet counts and kidney function, as well as hematologic normalization, complete TMA response, and TMA event-free status in a majority of patients.

The mortality rate is around 95% for untreated cases, but the prognosis is reasonably favorable (80–90% survival) for patients with idiopathic TTP diagnosed and treated early with plasmapheresis.

In general, AIHA in children has a good prognosis and is self-limiting. However, if it presents within the first two years of life or in the teenage years, the disease often follows a more chronic course, requiring long-term immunosuppression, with serious developmental consequences. The aim of therapy may sometimes be to lower the use of steroids in the control of the disease. In this case, splenectomy may be considered, as well as other immunosuppressive drugs. Infection is a serious concern in patients on long-term immunosuppressant therapy, especially in very young children (less than two years).

Secondary TTP is diagnosed when the patient's history mentions one of the known features associated with TTP. It comprises about 40% of all cases of TTP. Predisposing factors are:

- Cancer

- Bone marrow transplantation

- Pregnancy

- Medication use:

- Antiviral drugs (acyclovir)

- Certain chemotherapy medications such as gemcitabine and mitomycin C

- Quinine

- Oxymorphone

- Quetiapine

- Bevacizumab

- Sunitinib

- Platelet aggregation inhibitors (ticlopidine, clopidogrel, and prasugrel)

- Immunosuppressants (ciclosporin, mitomycin, tacrolimus/FK506, interferon-α)

- Hormone altering drugs (estrogens, contraceptives, hormone replacement therapy)

- HIV-1 infection

The mechanism of secondary TTP is poorly understood, as ADAMTS13 activity is generally not as depressed as in idiopathic TTP, and inhibitors cannot be detected. Probable etiology may involve, at least in some cases, endothelial damage, although the formation of thrombi resulting in vessel occlusion may not be essential in the pathogenesis of secondary TTP. These factors may also be considered a form of secondary aHUS; patients presenting with these features are, therefore, potential candidates for anticomplement therapy.

Acute PCH tends to be transient and self-limited, particularly in children. Chronic PCH associated with syphilis resolves after the syphilis is treated with appropriate antibiotics. Chronic idiopathic PCH is usually mild.

People with PCH are sometimes advised to avoid exposure to cold temperatures. If anemia is severe, blood transfusion may be needed. Careful compatibility testing by the blood bank is necessary because autoantibodies may interfere with blood typing. Prednisone may be used in individuals with PCH and severe anemia.

Prognosis varies depending on the underlying disorder, and the extent of the intravascular thrombosis (clotting). The prognosis for those with DIC, regardless of cause, is often grim: Between 20% and 50% of patients will die. DIC with sepsis (infection) has a significantly higher rate of death than DIC associated with trauma.

The causes of AIHA are poorly understood. The disease may be primary, or secondary to another underlying illness. The primary illness is idiopathic (the two terms used synonymously). Idiopathic AIHA accounts for approximately 50% of cases. Secondary AIHA can result from many other illnesses. Warm and cold type AIHA each have their own more common secondary causes. The most common causes of secondary warm-type AIHA include lymphoproliferative disorders (e.g., chronic lymphocytic leukemia, lymphoma) and other autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis, scleroderma, crohn's disease, ulcerative colitis). Less common causes of warm-type AIHA include neoplasms other than lymphoid, and infection. Secondary cold type AIHA is also caused primarily by lymphoproliferative disorders, but is also commonly caused by infection, especially by mycoplasma, viral pneumonia, infectious mononucleosis, and other respiratory infections. Less commonly, it can be caused by concomitant autoimmune disorders.

Drug-induced AIHA, though rare, can be caused by a number of drugs, including α-methyldopa and penicillin. This is a type II immune response in which the drug binds to macromolecules on the surface of the RBCs and acts as an antigen. Antibodies are produced against the RBCs, which leads to complement activation. Complement fragments, such as C3a, C4a and C5a, activate granular leukocytes (e.g., neutrophils), while other components of the system (C6, C7, C8, C9) either can form the membrane attack complex (MAC) or can bind the antibody, aiding phagocytosis by macrophages (C3b). This is one type of "penicillin allergy".

Hemolytic anemia affects nonhuman species as well as humans. It has been found, in a number of animal species, to result from specific triggers.

Some notable cases include hemolytic anemia found in black rhinos kept in captivity, with the disease, in one instance, affecting 20% of captive rhinos at a specific facility. The disease is also found in wild rhinos.

Dogs and cats differ slightly from humans in some details of their RBC composition and have altered susceptibility to damage, notably, increased susceptibility to oxidative damage from consumption of onion. Garlic is less toxic to dogs than onion.

DIC is observed in approximately 1% of academic hospital admissions. DIC occurs at higher rates in people with bacterial sepsis (83%), severe trauma (31%), and cancer (6.8%).

Overall prognosis is good in most patients, with one study showing recovery occurring in 94% and 89% of children and adults, respectively (some having needed treatment). In children under ten, the condition recurs in about a third of all cases and usually within the first four months after the initial attack. Recurrence is more common in older children and adults.

Acquired hemolytic anemia may be caused by immune-mediated causes, drugs and other miscellaneous causes.

- Immune-mediated causes could include transient factors as in "Mycoplasma pneumoniae" infection (cold agglutinin disease) or permanent factors as in autoimmune diseases like autoimmune hemolytic anemia (itself more common in diseases such as systemic lupus erythematosus, rheumatoid arthritis, Hodgkin's lymphoma, and chronic lymphocytic leukemia).

- Spur cell hemolytic anemia

- Any of the causes of hypersplenism (increased activity of the spleen), such as portal hypertension.

- Acquired hemolytic anemia is also encountered in burns and as a result of certain infections (e.g. malaria).

- Lead poisoning resulting from the environment causes non-immune hemolytic anemia.

- Runners can suffer hemolytic anemia due to "footstrike hemolysis", owing to the destruction of red blood cells in feet at foot impact.

- Low-grade hemolytic anemia occurs in 70% of prosthetic heart valve recipients, and severe hemolytic anemia occurs in 3%.

HSP occurs more often in children than in adults, and usually follows an upper respiratory tract infection. Half of affected patients are below the age of six, and 90% are under ten. It occurs about twice as often in boys as in girls. The incidence of HSP in children is about 20 per 100,000 children per year, making it the most common vasculitis in children.

Cases of HSP may occur anytime throughout the year, but some studies have found that fewer cases occur during the summer months.

Sickle-cell anaemia can lead to various complications, including:

- Increased risk of severe bacterial infections due to loss of functioning spleen tissue (and comparable to the risk of infections after having the spleen removed surgically). These infections are typically caused by encapsulated organisms such as "Streptococcus pneumoniae" and "Haemophilus influenzae". Daily penicillin prophylaxis is the most commonly used treatment during childhood, with some haematologists continuing treatment indefinitely. Patients benefit today from routine vaccination for "S. pneumoniae".

- Stroke, which can result from a progressive narrowing of blood vessels, prevents oxygen from reaching the brain. Cerebral infarction occurs in children and cerebral haemorrhage in adults.

- Silent stroke causes no immediate symptoms, but is associated with damage to the brain. Silent stroke is probably five times as common as symptomatic stroke. About 10–15% of children with SCD suffer strokes, with silent strokes predominating in the younger patients.

- Cholelithiasis (gallstones) and cholecystitis may result from excessive bilirubin production and precipitation due to prolonged haemolysis.

- Avascular necrosis (aseptic bone necrosis) of the hip and other major joints may occur as a result of ischaemia.

- Decreased immune reactions due to hyposplenism (malfunctioning of the spleen)

- Priapism and infarction of the penis

- Osteomyelitis (bacterial bone infection), the most common cause of osteomyelitis in SCD is "Salmonella" (especially the atypical serotypes "Salmonella typhimurium, Salmonella enteritidis, Salmonella choleraesuis" and "Salmonella paratyphi" B), followed by "Staphylococcus aureus" and Gram-negative enteric bacilli perhaps because intravascular sickling of the bowel leads to patchy ischaemic infarction.

- Acute papillary necrosis in the kidneys

- Leg ulcers

- In eyes, background retinopathy, proliferative retinopathy, vitreous haemorrhages, and retinal detachments can result in blindness. Regular annual eye checks are recommended.

- During pregnancy, intrauterine growth retardation, spontaneous abortion, and pre-eclampsia

- Chronic pain: Even in the absence of acute vaso-occlusive pain, many patients have unreported chronic pain.

- Pulmonary hypertension (increased pressure on the pulmonary artery) can lead to strain on the right ventricle and a risk of heart failure; typical symptoms are shortness of breath, decreased exercise tolerance, and episodes of syncope. 21% of children and 30% of adults have evidence of pulmonary hypertension when tested; this is associated with reduced walking distance and increased mortality.

- Chronic kidney failure due to sickle-cell nephropathy manifests itself with hypertension, protein loss in the urine, loss of red blood cells in urine and worsened anaemia. If it progresses to end-stage renal failure, it carries a poor prognosis.

The highest frequency of sickle cell disease is found in tropical regions, particularly sub-Saharan Africa, tribal regions of India and the Middle-East. Migration of substantial populations from these high prevalence areas to low prevalence countries in Europe has dramatically increased in recent decades and in some European countries sickle-cell disease has now overtaken more familiar genetic conditions such as haemophilia and cystic fibrosis. In 2015, it resulted in about 114,800 deaths.

Sickle-cell disease occurs more commonly among people whose ancestors lived in tropical and sub-tropical sub-Saharan regions where malaria is or was common. Where malaria is common, carrying a single sickle-cell allele (trait) confers a selective advantage—in other words, being a heterozygote is advantageous. Specifically, humans with one of the two alleles of sickle-cell disease show less severe symptoms when infected with malaria.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

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

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"

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.

At present there is no specific treatment. Many patients with haemolytic anaemia take folic acid (vitamin B) since the greater turnover of cells consumes this vitamin. During crises transfusion may be required. Clotting problems can occur for which anticoagulation may be needed. Unlike hereditary spherocytosis, splenectomy is contraindicated.

Theiler's disease, also known as idiopathic acute hepatitis disease (IAHD), serum-associated hepatitis, serum sickness, and postvaccinal hepatitis, is a viral hepatitis that affects horses. It is one of the most common cause of acute hepatitis and liver failure in the horse.

This is quite extensive and includes

- acute infectious hepatitis

- acute mycotoxicosis

- acute pyrrolizidine toxicosis

- acute infectious hepatitis

- acute mycotoxicosis

- haemolytic disease

- hepatotoxins

By definition, primary immune deficiencies are due to genetic causes. They may result from a single genetic defect, but most are multifactorial. They may be caused by recessive or dominant inheritance. Some are latent, and require a certain environmental trigger to become manifest, like the presence in the environment of a reactive allergen. Other problems become apparent due to aging of bodily and cellular maintenance processes.

The complement system is part of the innate as well as the adaptive immune system; it is a group of circulating proteins that can bind pathogens and form a membrane attack complex. Complement deficiencies are the result of a lack of any of these proteins. They may predispose to infections but also to autoimmune conditions.

1. C1q deficiency (lupus-like syndrome, rheumatoid disease, infections)

2. C1r deficiency (idem)

3. C1s deficiency

4. C4 deficiency (lupus-like syndrome)

5. C2 deficiency (lupus-like syndrome, vasculitis, polymyositis, pyogenic infections)

6. C3 deficiency (recurrent pyogenic infections)

7. C5 deficiency (Neisserial infections, SLE)

8. C6 deficiency (idem)

9. C7 deficiency (idem, vasculitis)

10. C8a deficiency

11. C8b deficiency

12. C9 deficiency (Neisserial infections)

13. C1-inhibitor deficiency (hereditary angioedema)

14. Factor I deficiency (pyogenic infections)

15. Factor H deficiency (haemolytic-uraemic syndrome, membranoproliferative glomerulonephritis)

16. Factor D deficiency (Neisserial infections)

17. Properdin deficiency (Neisserial infections)

18. MBP deficiency (pyogenic infections)

19. MASP2 deficiency

20. Complement receptor 3 (CR3) deficiency

21. Membrane cofactor protein (CD46) deficiency

22. Membrane attack complex inhibitor (CD59) deficiency

23. Paroxysmal nocturnal hemoglobinuria

24. Immunodeficiency associated with ficolin 3 deficiency

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".