Medullary Aplasia: Definition, Causes, Symptoms, Evolution, Diagnosis, Treatment and Consequences

It is a disease that affects the place of production of blood cells.

There are different types of blood cells: red blood cells, white blood cells or leukocytes, and platelets or thrombocytes.

These when produced in a normal way gradually replace the circulating cells destined to die naturally.

In this rare disease, the origin is a dysfunction of the bone marrow that makes it unable to produce red blood cells, white blood cells and platelets.

Like all cells, these are naturally renewed. New blood cells are continuously synthesized by the bone marrow from stem cells.

In the bone marrow, cells called “strains” present in small numbers are responsible for the production of blood cells.

In bone marrow aplasia, these stem cells disappear, so they can no longer guarantee their role in the renewal of blood cells, the number of which will therefore gradually and considerably decrease.

They ensure the daily renewal of these cells in about 100 billion per day in an adult.

Medullary aplasia causes a decrease in the number of blood cells and can be related to the rate of red blood cells, white blood cells and / or platelets.

General fatigue, weakness, recurrent infections, and abnormal bleeding can occur.

Idiopathic spinal cord aplasia is often referred to because its origin is unknown in the vast majority of cases.

Causes of spinal aplasia

In the vast majority of cases, the origin of this bone marrow pathology is unknown.

We speak of idiopathic medullary aplasia. However, research suggests that medullary aplasia is the consequence of an autoimmune phenomenon.

While the immune system generally destroys pathogens, it attacks healthy cells that are essential for the proper functioning of the body.

In the case of medullary aplasia, the immune defenses destroy the stem cells necessary for the production of new blood cells.

It is a disease acquired during life, it is not contagious.

Medullary aplasia is therefore not an inherited disease. However, if certain genes can predispose to its development, but carrying these genes does not necessarily mean that we will develop the disease.

These genes are thus qualified as susceptibility factors, the HLADR2 gene has been identified as such.

Because its origin is often unknown, it is called idiopathic aplastic anemia.

Several hypotheses are put forward to explain its causes:

Autoimmune origin

In some patients, immune factors produced in large quantities suggest that the cells of our immune system attack the stem cells of the bone marrow and destroy them

Hematopoietic stem cell deficiency

The stem cells responsible for blood cells can gradually disappear in aplasia, in this case we speak of the death of these stem cells.

Stem cell environment

In a minority of cases, the bone marrow stem cell environment is defective, which is what prevents their development.

The origin of medullary aplasia is therefore very difficult to determine, which also complicates the choice of treatment.

Risk factor’s

A rare disease with a hundred new cases per year, bone marrow suppression affects both men and women.

The average age is 30 years, however, it seems to be more present in the extreme ages of life, children or young adults and the elderly.

Among young adults, it appears that men are more affected, while the population over 50 has more women.

Aplasia is more common in Asia than in Europe or America.

Signs and Symptoms of Medullary Aplasia

Medullary aplasia can appear suddenly or gradually and set in without the patient noticing. Depending on the type of blood cells affected, the signs are different.

Red blood cells

Anemia refers to the lack of red blood cells in the blood, which causes an inadequate supply of oxygen in the body. The signs of this anemia are:

  • Pale skin, mucous membranes, tongue, gums, and possible conjunctiva (membrane that covers the white of the eye).
  • Greater non-reversible fatigue with rest.
  • Shortness of breath, dizziness, heart palpitations on exertion.
  • Possible muscle aches (sensation of tetanized muscles).
  • Dull and dry skin, hair loss and diminished shine and silky character.
  • Brittle nails

White blood cells

Unexplained fever or repeated infections are signs of a decrease in white blood cells, which, therefore, can no longer guarantee the defense of our body.

The infections are often angina or furunculosis (skin infections characterized by the appearance of purulent pimples or boils).


When the number of platelets decreases, abnormal bleeding can occur mainly in the nose or gums, as well as frequent and unexplained bruising.

Bleeds may also appear on the skin, called purpura (small purplish-red spots that range in size from a pinhead to a lens).

Diagnosis of medullary aplasia

A blood test is done to evaluate the levels of different types of cells (red blood cells, white blood cells, platelets).

The severity of the disease is evaluated by the Camitta criteria:

  • Polynuclear <500 / mm3, under which the risk of infection becomes severe.
  • Platelets <20,000 / mm3, under which the risk of bleeding is high.
  • Hemoglobin <8 g / dl, under which anemia becomes painful for the organs.

The diagnosis is based on a series of tests, looking for an insufficient number of cells in the blood and bone marrow such as:

A blood count

Performed through blood tests that allow evaluating the amount of white, red blood cells and platelets present in the blood.

A spinal tap

Performed under local anesthesia and involves the introduction of a large needle at the level of the iliac bone (hip) or sternum to take a bone marrow sample.

The objective of this sampling is to estimate the regenerative capacities of the bone marrow and to evaluate the degree of damage.

A bone marrow biopsy

This consists of taking a piece of bone in the upper part of the pelvis.

These tests are essential because they allow to rule out other important pathologies such as myelodysplasias, leukemias or lymphomas.

Other tests, such as looking for bacterial or viral agents, may be done due to the high risk of infection.

To prepare for the introduction of treatments such as blood transfusion or bone marrow transplantation, blood tests are performed routinely.

It is not possible to detect this disease until the first symptoms appear.

Evolution of medullary aplasia

Without treatment, bone marrow aplasia is unpredictable, but symptoms and severity differ from patient to patient.

Sometimes the symptoms are mild and simple monitoring is sufficient.

Most of the time, the evolution is towards a chronic state in which recurrent infections and hemorrhages of variable severity occur.

Therefore, bone marrow suppression is responsible for infections or bleeding that can be life threatening.

However, recent advances in treatment can significantly improve longevity for patients.

Other concomitant diseases with aplasia may also occur.

This is the case with paroxysmal nocturnal hemoglobinuria, which occurs in 30–40% of patients treated with immunosuppressive agents, but remains mostly asymptomatic.

Aplasia can also transform into myelodysplasia or acute leukemia, but they are not common.

In some cases, however, spontaneous healing (remission) can occur after a few years of evolution.


The management of aplastic anemia depends on its evolution. The choice of treatment is made according to the benefits and risks of each technique for the patient.

If simple medical supervision can sometimes be enough, treatment is necessary in most cases.

There are currently two types of standard treatments that can be considered to treat bone marrow failure:

Immunosuppressive therapy

It is based on drugs that can suppress the immune system to limit or even stop the destruction of stem cells.

These are medications commonly used in the care of autoimmune diseases.

Immunosuppressive therapy is usually prescribed first, and it can be effective, but the results are not immediate, usually a 3-month delay is seen before improvement is seen.

Anti-lymphocyte serum is the gold standard treatment, it is very often associated with cyclosporine and / or corticosteroids.

On average, there is an improvement in 2-year survival in 70-80% of treated patients.

Patients who have not responded sufficiently can be treated again with immunosuppressants.

The main risk of this treatment is infection, since immunosuppressants and corticosteroids further reduce the body’s defenses.

The deficit of white blood cells already present must be closely monitored, the use of transfusion may be necessary.

It can also weaken the bone marrow and later create complications.

Other side effects related to the use of corticosteroids may also appear, such as:

  • Waterfalls.
  • Hypertension.
  • Hormonal and sleep disorders.
  • Loss of muscle mass.
  • Hematomas.
  • Osteoporosis.
  • Digestive disorders and weight gain.

Bone marrow transplant

This is an intense treatment that is not without the risk of postoperative complications.

Transplantation is the only truly curative treatment. It involves replacing the patient’s bone marrow with that of a compatible donor, which will produce normal blood cells (red cells, white cells, and platelets).

Although bone marrow transplantation is currently the most effective treatment for bone marrow aplasia, this operation is only considered under certain conditions.

It is generally offered as a first choice in young patients (under 40-50 years) with a very severe form of the disease, as well as a related donor.

This is most often a brother or sister because the match rate is the highest, 1 in 4.

In the absence of a related donor, the graft is indicated only as a second option, then a search is carried out in the national or international donor archive.

This intense treatment can lead to serious complications, but healing occurs in 70-80% of cases after 5 years.

Another technique, umbilical cord blood transplantation can also be offered especially in children.

In general, bone marrow transplantation is reserved for patients under 40 years of age with a severe form of bone marrow suppression.

Supportive treatments may be offered to control symptoms of bone marrow suppression, such as:

  • Antibiotics to prevent or treat certain infections.
  • Red blood cell transfusions in case of anemia.
  • Platelet transfusions during thrombocytopenia.
After transplant

When a transplant has been performed, the patient has not yet recovered an effective immune system and must remain in a sterile room for several weeks to limit the risk of infection.

He is under surveillance and especially due to hemorrhagic, infectious and anemic risks.

The main complication is the possibility of transplant rejection (10% of cases), the patient’s immune system does not accept the transplant cells and destroys them. This can happen quickly or in the next 2 to 3 years.

In an attempt to overcome this problem, immunosuppressive therapy (antithymocyte globulin, cyclosporine, and cyclophosphamide) is prescribed.

In some cases, the grafted cells can turn against the patient’s body because they are immune cells that do not recognize the patient’s cells and want to destroy them.

It’s called a graft-versus-host reaction, which occurs only when there is an incompatibility between the donor and the patient, or when the patient has a severely weakened immune system.

Supportive treatments

These treatments help prevent or treat the risks of aplasia:

  • Risks related to anemia: transfusion of red blood cell granules to maintain hemoglobin above 8 g / l.
  • Bleeding risk: platelet transfusion to maintain a rate greater than 10-20000.
  • Risks of infection: any episode of fever, when neutrophils are greater than 500, is a therapeutic emergency that requires antibiotic coverage.

Growth factors in some cases stimulate the renewal and development of blood cells.

For red blood cells, different types of erythropoietin can be prescribed. For white blood cells, these are granulocyte-active proteins: G-CSF, GM-CSF.

Spinal aplasia is monitored in the hospital in consultation with specialized hematology and immunohematology.

Marrow transplant units monitor transplant recipients.

Consequences of spinal aplasia

The consequences can vary from person to person. The decrease in blood cells can be progressive or sudden.

Also, different cell types are not necessarily impacted in the same way.

The consequences of aplasia are different depending on the type of deficient cells:

Red blood cells

They are responsible for the transport and distribution of oxygen in the body. During a deficiency in red blood cells, anemia appears.

White blood cells

They are the body’s defense system against foreign organisms (viruses, bacteria, fungi, among others).

Leukopenia is a decrease in white blood cells that participate in the body’s immune defense;

When their numbers are not enough, our body cannot defend itself and infections can appear.


They allow blood to clot and play a vital role in stopping bleeding.

Thrombocytopenia is a decrease in the levels of platelets in the blood.

The deficiency causes bleeding disorders in the event of injury and consequently leads to bleeding.

Depending on the type of cell line affected, the consequences can be multiple.