Aplastic anemia

Definitions & Key takeaways

Aplastic anemia is a rare blood disorder caused by bone marrow failure to produce new blood cells. Even though it's referred to as aplastic anemia, it typically presents with pancytopenia, meaning that all three major blood cell lines - the red blood cells, white blood cells, and platelets are affected.

People with aplastic anemia may experience fatigue, shortness of breath, ecchymoses and mucosal bleeding, and frequent infections pallor Aplastic anemia can be caused by a variety of factors, including exposure to radiation or chemotherapy, viral infections, and autoimmune disorders.

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Introduction0:00–0:32

Aplastic anemia is a pancytopenia, meaning all blood cell lines are decreased - so the term aplastic anemia, which just refers to low red blood cell count, is actually a misnomer.
So with aplastic anemia, there’s actually anemia, as well as leukocytopenia, or low white blood cells, as well as thrombocytopenia, or low platelet levels.
This condition takes many forms, ranging from mild to severe depending on the cause. Now, blood cells are produced in the bones of the body, mainly in the bones of the pelvis, ribs and sternum, through a process called hematopoiesis.

Physiology0:32–1:31

This process starts in the bone marrow, the innermost portion of bone, where the hematopoietic stem cells reside. These serve as progenitor cells for all the different cell types found in the blood.
First, hematopoietic stem cells, also called hemocytoblasts, can become lymphoid progenitors or myeloid progenitors. The lymphoid progenitors can develop into lymphoblasts, which can then differentiate into some white blood cells like T-lymphocytes, B-lymphocytes, or natural killer cells.
The myeloid progenitors can differentiate into erythrocytes, or red blood cells, megakaryocytes, which eventually give rise to platelets, or myeloblasts, which can then become other white blood cells like monocytes, neutrophils, basophils, and eosinophils.

Causes1:31–3:49

The most common cause of aplastic anemia is autoimmune destruction of hematopoietic stem cells. The details of this mechanism are not fully understood, but research shows that there are alterations in the immunologic appearance of hematopoietic stem cells because of genetic disorders, or after exposure to environmental agents, like radiation or toxins.
This means that the hematopoietic stem cells start expressing non-self antigens and the immune system subsequently targets them for destruction.As the immune system destroys hematopoietic stem cells a whole host of complications arise.
Due to the low red blood cell count tissues cannot properly oxygenate so the heart pumps harder to circulate the red blood cells leading to chest pain and shortness of breath.
Low platelet counts lead to an increased risk of bleeding from the most minor injuries and in mucosal areas. Low white blood cells counts lead to the body’s inability to fight off common infections that can lead to sepsis.
Now, there are many causes of aplastic anemia, but the disease is most often idiopathic, or without an identifiable cause.
Definable causes of aplastic anemia include radiation and toxins like insecticides or industrial agents that contain benzene.
Drugs that may cause aplastic anemia include chemotherapeutic agents, anti-seizure medications, antiinflammatory medications like indomethacin, antithyroid medications like propylthiouracil and methimazole, and antibiotics like chloramphenicol and sulfonamides.
Infectious agents like the epstein-barr virus, or HIV, and clonal or genetic disorders can also cause aplastic anemia.Finally, the most common genetic disorders associated with aplastic anemia is Fanconi’s anemia.
Fanconi's anemia is the most common inherited cause of aplastic anemia, which is a condition characterized by pancytopenia, predisposition to malignancy, and physical abnormalities like short stature, microcephaly, or a small head, developmental delay, café-au-lait skin lesions, and absent or hypoplastic thumbs.

Symptoms3:49–4:03

Symptoms of aplastic anemia include fatigue, pallor on account on low red blood cell levels, mucosal bleeding or petechiae due to low platelet counts, and recurrent infections due to low white blood cell counts.

Diagnosis4:03–5:09

Aplastic anemia may be suspected based on a complete blood cell count, which shows low red blood cell counts,, leukocytopenia and thrombocytopenia.
Erythropoietin, or EPO, levels are also increased. EPO is a hormone released by the kidney that tells hematopoietic stem cells to grow and divide into new red blood cells.
With aplastic anemia, there aren’t enough hematopoietic stem cells to generate appropriate amounts of red blood cells, so more and more EPO gets produced in an attempt to compensate.
There may also be a decreased reticulocyte count. Reticulocytes are young red blood cells, so this demonstrates decreased red blood cell production.
Bleeding time may also be increased due to low platelet counts. Definitive diagnosis requires a bone marrow biopsy which demonstrates profoundly low counts of hematopoietic stem cells with a normal cellular morphology in the absence of any infiltrative disorder like malignancy or fibrosis.
This is also referred to as an empty marrow, or dry tap.Treatment of aplastic anemia is largely dependent on the age of the person affected, as well as the clinical history.

Treatment5:09–5:48

If the condition is thought to be due to a medication or toxin, these substances or exposures should be removed from the affected person immediately.
For people under the age of fifty, first line therapy is a stem cell transplant. For those greater than age fifty, first line therapy is immunosuppressive therapy, with medications like cyclosporine or glucocorticoids, as well as medications that help to stimulate increased hematopoiesis like granulocyte colony-stimulating factor.
Blood transfusions may be necessary for severe cases.##SummaryAll right, as a quick recap, Aplastic anemia is actually a form of pancytopenia that results from autoimmune destruction of hematopoietic stem cells.

Review5:48–6:20

Low red blood cell numbers cause poor tissue oxygenation, low white blood cells cause an increased susceptibility to infections, while low platelets lead to an increased risk of bleeding from the most minor injuries and in mucosal areas.
Most often, aplastic anemia is caused by medications, toxins, viruses, and genetic disorders. Treatment involves either stem cell