Bone marrow failure in both children and adults can be either inherited or acquired. Inherited bone marrow failure is often the cause in young children, while older children and adults may acquire the disease later in life. A maturation defect in genes is a common cause of inherited bone marrow failure. The most common cause of acquired bone marrow failure is aplastic anemia. Working with chemicals such as benzene could be a factor in causing the illness. Other factors include radiation or chemotherapy treatments, and immune system problems.

Untreated, severe aplastic anemia has a high risk of death. Modern treatment, by drugs or stem cell transplant, has a five-year survival rate that exceeds 85%, with younger age associated with higher survival.

Survival rates for stem cell transplant vary depending on age and availability of a well-matched donor. Five-year survival rates for patients who receive transplants have been shown to be 82% for patients under age 20, 72% for those 20–40 years old, and closer to 50% for patients over age 40. Success rates are better for patients who have donors that are matched siblings and worse for patients who receive their marrow from unrelated donors.

Older people (who are generally too frail to undergo bone marrow transplants), and people who are unable to find a good bone marrow match, undergoing immune suppression have five-year survival rates of up to 75%.

Relapses are common. Relapse following ATG/ciclosporin use can sometimes be treated with a repeated course of therapy. In addition, 10-15% of severe aplastic anemia cases evolve into MDS and leukemia. According to a study, for children who underwent immunosuppressive therapy, about 15.9% of children who responded to immunosuppressive therapy encountered relapse.

Milder disease can resolve on its own.

The two most common signs and symptoms of bone marrow failure are bleeding and bruising. Blood may be seen throughout the gums, nose or the skin, and tend to last longer than normal. Children have a bigger chance of seeing blood in their urine or stools, which results in digestive problems with an unpleasant scent. Individuals with this condition may also encounter tooth loss or tooth decay. Chronic fatigue, shortness of breath, and recurrent colds can also be symptoms of bone marrow failure.

Myelophthisis can occur in the setting of chronic myeloproliferative disease (e.g. myelofibrosis), leukemia, lymphoma, and metastatic carcinoma or myeloma. It is common in people who have chronic idiopathic myelofibrosis. It has been linked to small-cell lung cancer, breast cancer or prostate cancer that metastasizes to the bone marrow.

Historically, the most common cause of displacement of healthy bone marrow was tuberculosis.

Currently, the most common cause is displacement of bone marrow by metastatic cancer (extramedullary hematopoiesis tends to be modest). Other causes include myeloproliferative disorders (especially late-stage or spent polycythemia vera), granulomatous diseases, and (lipid) storage diseases. Myelofibrosis can occur in all of these.

Factors that may contribute to decreased RBC production include a decreased quantity of functioning hematopoietic tissue, disordered metabolism related to the underlying disorder, and, in some cases, erythrophagocytosis.

Aplastic anemia can be caused by exposure to certain chemicals, drugs, radiation, infection, immune disease; in about half the cases, yet a defintive cause is unknown. It is not a familial line hereditary condition, nor is it contagious. It can be acquired due to exposure to other conditions but if a person develops the condition, their offspring would not develop it by virtue of their gene connection.

Aplastic anemia is also sometimes associated with exposure to toxins such as benzene, or with the use of certain drugs, including chloramphenicol, carbamazepine, felbamate, phenytoin, quinine, and phenylbutazone. Many drugs are associated with aplasia mainly according to case reports, but at a very low probability. As an example, chloramphenicol treatment is followed by aplasia in less than one in 40,000 treatment courses, and carbamazepine aplasia is even rarer.

Exposure to ionizing radiation from radioactive materials or radiation-producing devices is also associated with the development of aplastic anemia. Marie Curie, famous for her pioneering work in the field of radioactivity, died of aplastic anemia after working unprotected with radioactive materials for a long period of time; the damaging effects of ionizing radiation were not then known.

Aplastic anemia is present in up to 2% of patients with acute viral hepatitis.

One known cause is an autoimmune disorder in which white blood cells attack the bone marrow.

Short-lived aplastic anemia can also be a result of parvovirus infection. In humans, the P antigen (also known as globoside), one of the many cellular receptors that contribute to a person's blood type, is the cellular receptor for parvovirus B19 virus that causes erythema infectiosum (fifth disease) in children. Because it infects red blood cells as a result of the affinity for the P antigen, Parvovirus causes complete cessation of red blood cell production. In most cases, this goes unnoticed, as red blood cells live on average 120 days, and the drop in production does not significantly affect the total number of circulating red blood cells. In people with conditions where the cells die early (such as sickle cell disease), however, parvovirus infection can lead to severe anemia.

More frequently parvovirus B19 is associated with aplastic crisis which involves only the red blood cells ( despite the name). Aplastic anemia involves all different cell lines.

In some animals, aplastic anemia may have other causes. For example, in the ferret ("Mustela putorius furo"), it is caused by estrogen toxicity, because female ferrets are induced ovulators, so mating is required to bring the female out of heat. Intact females, if not mated, will remain in heat, and after some time the high levels of estrogen will cause the bone marrow to stop producing red blood cells.

Bone marrow suppression due to azathioprine can be treated by changing to another medication such as mycophenolate mofetil (for organ transplants) or other disease-modifying drugs in rheumatoid arthritis or Crohn's disease.

Some cases of myelophthisis are thought to be related to the release of cytokines that simulate fibroblastic proliferation and fibrosis in the marrow.

Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (thrombocytes). Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine. The risk is especially high in cytotoxic chemotherapy for leukemia.

Nonsteroidal anti-inflammatory drugs (NSAIDs), in some rare instances, may also cause bone marrow suppression. The decrease in blood cell counts does not occur right at the start of chemotherapy because the drugs do not destroy the cells already in the bloodstream (these are not dividing rapidly). Instead, the drugs affect new blood cells that are being made by the bone marrow. When myelosuppression is severe, it is called myeloablation.

Because the bone marrow is the manufacturing center of blood cells, the suppression of bone marrow activity causes a deficiency of blood cells. This condition can rapidly lead to life-threatening infection, as the body cannot produce leukocytes in response to invading bacteria and viruses, as well as leading to anaemia due to a lack of red blood cells and spontaneous severe bleeding due to deficiency of platelets.

Parvovirus B19 inhibits erythropoiesis by lytically infecting RBC precursors in the bone marrow and is associated with a number of different diseases ranging from benign to severe. In immunocompromised patients, B19 infection may persist for months, leading to chronic anemia with B19 viremia due to chronic marrow suppression.

PNH is rare, with an annual rate of 1-2 cases per million. The prognosis without disease-modifying treatment is 10–20 years. Many cases develop in people who have previously been diagnosed with aplastic anemia or myelodysplastic syndrome. The fact that PNH develops in MDS also explains why there appears to be a higher rate of leukemia in PNH, as MDS can sometimes transform into leukemia.

25% of female cases of PNH are discovered during pregnancy. This group has a high rate of thrombosis, and the risk of death of both mother and child are significantly increased (20% and 8% respectively).

Controversy remains today whether this disorder is a subtype of acute myeloid leukemia or myelodysplastic syndromes; however, it is currently classified as a form of AML.

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.

Some people have a history of exposure to chemotherapy (especially alkylating agents such as melphalan, cyclophosphamide, busulfan, and chlorambucil) or radiation (therapeutic or accidental), or both (e.g., at the time of stem cell transplantation for another disease). Workers in some industries with heavy exposure to hydrocarbons such as the petroleum industry have a slightly higher risk of contracting the disease than the general population. Xylene and benzene exposure has been associated with myelodysplasia. Vietnam veterans exposed to Agent Orange are at risk of developing MDS. A link may exist between the development of MDS "in atomic-bomb survivors 40 to 60 years after radiation exposure" (in this case, referring to people who were in close proximity to the dropping of the atomic bomb in Hiroshima and Nagasaki during World War II).

Children with Down syndrome are susceptible to MDS, and a family history may indicate a hereditary form of sideroblastic anemia or Fanconi anemia.

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%.

Although not yet formally incorporated in the generally accepted classification systems, molecular profiling of myelodysplastic syndrome genomes has increased the understanding of prognostic molecular factors for this disease. For example, in low-risk MDS, "IDH1" and "IDH2" mutations are associated with significantly worsened survival.

Sideroblastic anemias are often described as responsive or non-responsive in terms of increased hemoglobin levels to pharmacological doses of vitamin B.

1- Congenital: 80% are responsive, though the anemia does not completely resolve.

2- Acquired clonal: 40% are responsive, but the response may be minimal.

3- Acquired reversible: 60% are responsive, but course depends on treatment of the underlying cause.

Severe refractory sideroblastic anemias requiring regular transfusions and/or that undergo leukemic transformation (5-10%) significantly reduce life expectancy.

Many patients eventually develop acute myelogenous leukemia (AML). Older patients are extremely likely to develop head and neck, esophageal, gastrointestinal, vulvar and anal cancers. Patients who have had a successful bone marrow transplant and, thus, are cured of the blood problem associated with FA still must have regular examinations to watch for signs of cancer. Many patients do not reach adulthood.

The overarching medical challenge that Fanconi patients face is a failure of their bone marrow to produce blood cells. In addition, Fanconi patients normally are born with a variety of birth defects. A good number of Fanconi patients have kidney problems, trouble with their eyes, developmental retardation and other serious defects, such as microcephaly (small head).

Causes of sideroblastic anemia can be categorized into three groups: congenital sideroblastic anemia, acquired clonal sideroblastic anemia, and acquired reversible sideroblastic anemia. All cases involve dysfunctional heme synthesis or processing. This leads to granular deposition of iron in the mitochondria that form a ring around the nucleus of the developing red blood cell. Congenital forms often present with normocytic or microcytic anemia while acquired forms of sideroblastic anemia are often normocytic or macrocytic.

- Congenital sideroblastic anemia

- X-linked sideroblastic anemia: This is the most common congenital cause of sideroblastic anemia and involves a defect in ALAS2, which is involved in the first step of heme synthesis. Although X-linked, approximately one third of patients are women due to skewed X-inactivation (lyonizations).

- Autosomal recessive sideroblastic anemia involves mutations in the SLC25A38 gene. The function of this protein is not fully understood, but it is involved in mitochondrial transport of glycine. Glycine is a substrate for ALAS2 and necessary for heme synthesis. The autosomal recessive form is typically severe in presentation.

- Genetic syndromes: Rarely, sideroblastic anemia may be part of a congenital syndrome and present with associated findings, such as ataxia, myopathy, and pancreatic insufficiency.

- Acquired clonal sideroblastic anemia

- Clonal sideroblastic anemias fall under the broader category of myelodysplastic syndromes (MDS). Three forms exist and include refractory anemia with ringed sideroblasts (RARS), refractory anemia with ringed sideroblasts and thrombocytosis (RARS-T), and refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS). These anemias are associated with increased risk for leukemic evolution.

- Acquired reversible sideroblastic anemia

- Causes include excessive alcohol use (the most common cause of sideroblastic anemia), pyridoxine deficiency, lead poisoning, and copper deficiency. Excess zinc can indirectly cause sideroblastic anemia by decreasing absorption and increasing excretion of copper. Antimicrobials that may lead to sideroblastic anemia include isoniazid, chloramphenicol, cycloserine, and linezolid.

CDA type I is characterized by moderate to severe anemia. It is usually diagnosed in childhood or adolescence, although in some cases, the condition can be detected before birth.

Thrombocytopenia affects a few percent of newborns, and its prevalence in neonatal intensive care units (NICU) is high. Normally, it is mild and resolves without consequences. Most cases affect preterm birth infants and result from placental insufficiency and/or fetal hypoxia. Other causes, such as alloimmunity, genetics, autoimmunity, and infection, are less frequent.

Thrombocytopenia that starts after the first 72 hours since birth is often the result of underlying sepsis or necrotizing enterocolitis (NEC). In the case of infection, PCR tests may be useful for rapid pathogen identification and detection of antibiotic resistance genes. Possible pathogens include viruses (e.g. Cytomegalovirus (CMV), rubella virus, HIV), bacteria (e.g. "Staphylococcus sp.", "Enterococcus sp.", "Streptococcus agalactiae" (GBS), "Listeria monocytogenes", "Escherichia coli", "Haemophilus influenzae", "Klebsiella pneumoniae", "Pseudomonas aeruginosa", "Yersinia enterocolitica"), fungi (e.g. "Candida sp."), and "Toxoplasma gondii". The severity of thrombocytopenia may be correlated with pathogen type; some research indicates that the most severe cases are related to fungal or gram-negative bacterial infection. The pathogen may be transmitted during or before birth, by breast feeding, or during transfusion. Interleukin-11 is being investigated as a drug for managing thrombocytopenia, especially in cases of sepsis or necrotizing enterocolitis (NEC).

The primary treatment for CAMT is bone marrow transplantation.

Bone Marrow/Stem Cell Transplant is the only thing that ultimately cures this genetic disease. Frequent platelet transfusions are required to ensure that platelet levels do not fall to dangerous levels, although this is not always the case. It is known for patients to continue to create very small numbers of platelets over time.

The last major haematological complication associated with FA is bone marrow failure, defined as inadequate blood cell production. Several types of failure are observed in FA patients, and generally precede MDS and AML. Detection of decreasing blood count is generally the first sign used to assess necessity of treatment and possible transplant. While most FA patients are initially responsive to androgen therapy and haemopoietic growth factors, these have been shown to promote leukemia, especially in patients with clonal cytogenetic abnormalities, and have severe side effects, including hepatic adenomas and adenocarcinomas. The only treatment left would be bone marrow transplant; however, such an operation has a relatively low success rate in FA patients when the donor is unrelated (30% 5-year survival). It is, therefore, imperative to transplant from an HLA-identical sibling. Furthermore, due to the increased susceptibility of FA patients to chromosomal damage, pretransplant conditioning cannot include high doses of radiation or immunosuppressants, thus increased chances of patients developing graft-versus-host disease. If all precautions are taken, and the marrow transplant is performed within the first decade of life, two-year probability of survival can be as high as 89%. However, if the transplant is performed at ages older than 10, two-year survival rates drop to 54%.

A recent report by Zhang et al. investigates the mechanism of bone marrow failure in FANCC-/- cells. They hypothesize and successfully demonstrate that continuous cycles of hypoxia-reoxygenation, such as those seen by haemopoietic and progenitor cells as they migrate between hyperoxic blood and hypoxic marrow tissues, leads to premature cellular senescence and therefore inhibition of haemopoietic function. Senescence, together with apoptosis, may constitute a major mechanism of haemopoietic cell depletion occurred in bone marrow failure.

A large number of drugs

have been associated with agranulocytosis, including antiepileptics (such as carbamazepine and valproate), antithyroid drugs (carbimazole, methimazole, and propylthiouracil), antibiotics (penicillin, chloramphenicol and co-trimoxazole), ACE inhibitors (benazepril), cytotoxic drugs, gold, NSAIDs (indomethacin, naproxen, phenylbutazone, metamizole), mebendazole, allopurinol the antidepressants mianserin and mirtazapine, and some antipsychotics (the atypical antipsychotic clozapine in particular). Clozapine users in the United States, Australia, Canada, and the UK must be nationally registered for monitoring of low WBC and absolute neutrophil counts (ANC).

Although the reaction is generally idiosyncratic rather than proportional, experts recommend that patients using these drugs be told about the symptoms of agranulocytosis-related infection, such as a sore throat and a fever.

The Centers for Disease Control traced outbreaks of agranulocytosis among cocaine users, in the US and Canada between March 2008 and November 2009, to the presence of levamisole in the drug supply. The Drug Enforcement Administration reported that, as of February 2010, 71% of seized cocaine lots coming into the US contained levamisole as a cutting agent. Levamisole is an antihelminthic (i.e. deworming) drug used in animals. The reason for adding levamisole to cocaine is unknown, although it can be due to their similar melting points and solubilities.

Refractory cytopenia of childhood (RCC) is a subgroup of myelodysplastic syndrome (MDS), having been added to the World Health Organization classification in 2008. Before then, RCC cases were classified as childhood aplastic anemia. RCC is the most common form of MDS in children and adolescents, accounting for approximately half of all MDS cases.

The following medications can induce thrombocytopenia through direct myelosuppression.

- Valproic acid

- Methotrexate

- Carboplatin

- Interferon

- Isotretinoin

- Panobinostat

- H blockers and proton-pump inhibitors

This is a rare disease, with less than 100 cases reported. Of these cases, an equal male:female ratio was observed,

with cases typically seen in older adults.