Reticulocytopenia is the medical term for an abnormal decrease in circulating red blood cell precursors (
reticulocytes) that can lead to
anemia
Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
due to resulting low red blood cell (
erythrocyte
Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood ce ...
) production.
Reticulocytopenia may be an isolated finding or it may not be associated with abnormalities in other hematopoietic cell lineages such as those that produce white blood cells (
leukocytes
White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
) or
platelet
Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...
s (thrombocytes), a decrease in all three of these lineages is referred to as
pancytopenia
Pancytopenia is a medical condition in which there is significant reduction in the number of almost all blood cells (red blood cells, white blood cells, platelets, monocytes, lymphocytes, etc.).
If only two parameters from the complete blood cou ...
.
With isolated reticulocytopenia, the main cause is
Parvovirus B19 infection of reticulocytes leading to transient anemia.
In patients who rely on frequent red cell regeneration e.g.
sickle cell disease
Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited Hemoglobinopathy, haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the ...
, a reticulocytopenia can lead to a severe anemia due to the cessation in red cell production (
erythropoiesis
Erythropoiesis (from Greek ''erythro'', meaning ''red'' and ''poiesis'', meaning ''to make'') is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.
It is s ...
), referred to as aplastic crisis.
If pancytopenia is present,
bone marrow
Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...
failure
must be considered and evaluation for bone marrow failure syndromes or
aplastic anemia must be pursued. Treatment is dependent on the etiology and may include replacement of
blood products as patients can develop severe anemia.
Differential Diagnosis
Reticulocytopenia may be associated with abnormalities in other
hematopoietic cell lineages. The following is a differential diagnosis for patients in which reticulocytopenia is the most marked cytopenia. For conditions that lead to significant reduction in all three cell lineages, see
pancytopenia
Pancytopenia is a medical condition in which there is significant reduction in the number of almost all blood cells (red blood cells, white blood cells, platelets, monocytes, lymphocytes, etc.).
If only two parameters from the complete blood cou ...
or
aplastic anemia.
*
Parvovirus B19 infection
*
Transient Erythroblastopenia of Childhood
*
Pure red cell aplasia
* Hereditary bone marrow failure syndromes
**
Diamond-Blackfan anemia (congenital pure red cell aplasia)
**
Pearson marrow-pancreas syndrome
**
Congenital dyserythropoietic anemia
*
Malnutrition
Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is a deficiency, excess, or imbalance of energy, protein and other nutrients which adversely affects the body's tissues a ...
- (e.g. deficiencies in
B12,
folate
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
,
iron
Iron is a chemical element; it has symbol Fe () and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, forming much of Earth's o ...
)
* Sequelae of malignancy, connective tissue disease, autoimmune disease
* Adverse effect of medication
Pathophysiology
The specific pathophysiology differs with each etiology. For conditions that lead to pancytopenia, see
aplastic anemia.
Parvovirus B-19 Infection
Parvovirus is able to infiltrate the bone marrow and enter and replicate in red blood cell precursors such as reticulocytes.
Viral replication in reticulocytes causes
apoptosis
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
(cell death) of affected cells.
The reduction in living reticulocytes leads to a decrease in red blood cell production. This transient cessation in red cell production results in a decrease in hemoglobin that is often asymptomatic in people without underlying hematologic disorders. Reticulocyte production often recovers within one week. Parvovirus infection in people reliant on frequent red cell production due to low baseline production or high turnover rates are at risk of developing a life-threatening condition called aplastic crisis (see below).
Bone Marrow Failure Syndromes
Bone marrow failure syndromes may be acquired or inherited. These conditions lead to a decrease in one or more cell lineages. Diamond-Blackfan Anemia is an example of a congenital bone marrow failure syndrome that primarily affects red blood cell production. In DBA, the erythroid cell lineage is more susceptible to cell death due to abnormal ribosome function.
This leads to a reduced population of red blood cell precursors and a resulting reticulocytopenia and anemia.
Evaluation
For the patient with isolated reticulocytopenia and anemia without significant disturbances in other cell lineages, the initial evaluation may include some of the following studies:
*
Complete blood count
A complete blood count (CBC), also known as a full blood count (FBC) or full haemogram (FHG), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blo ...
with differential
*
Peripheral blood smear
A blood smear, peripheral blood smear or blood film is a thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allow the various blood cells to be examined microscopically. Blood smears are examined in the i ...
*
Type and Cross (in case transfusion is needed)
*
Reticulocyte Production Index
Further Evaluation
Depending on findings on initial evaluation, may consider investigating the cause of low reticulocyte count with some of the following studies depending on patient presentation and differential diagnoses:
*
Bone marrow aspiration and evaluation
* Parvovirus B19 IgG/IgM
*
Erythropoietin
Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production ( erythropoiesis) in th ...
level
* Rheumatalogic studies
* Viral studies in addition to Parvovirus B19
* B12, Folate levels, iron studies
* Specialized tests if there is concern for hereditary bone marrow failure syndrome
Management
The goal is to treat the underlying condition if it can be identified and provide supportive care. If symptomatic anemia develops, blood products may be replaced. Disease specific management may include glucocorticoids, IVIG, immunosuppressive agents, stem cell transplant, or other treatments depending on the etiology of reticulocytopenia.
Complications
Anemia
Severe anemia can lead to complications such as
heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood.
Although symptoms vary based on which side of the heart is affected, HF ...
due to volume overload, bone marrow necrosis, etc. See
anemia
Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...
for further details.
Aplastic Crisis
Transient decrease in
erythropoiesis
Erythropoiesis (from Greek ''erythro'', meaning ''red'' and ''poiesis'', meaning ''to make'') is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.
It is s ...
resulting in low reticulocyte count with decrease in
hemoglobin
Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. Hemoglobin ...
>/= 3 g/dL is considered to be aplastic crisis.
For the decrease in all cell lineages (
pancytopenia
Pancytopenia is a medical condition in which there is significant reduction in the number of almost all blood cells (red blood cells, white blood cells, platelets, monocytes, lymphocytes, etc.).
If only two parameters from the complete blood cou ...
), see
aplastic anemia. The majority of cases of aplastic crisis are seen in people with hematologic disorders and superimposed infection with
Parvovirus B19.
Predisposing Conditions
Patients who rely on frequent regeneration of RBCs due to shorter RBC lifespan or decreased production are at risk of developing aplastic crisis when erythropoiesis is affected as they cannot compensate for the lapse in red cell production. A typical erythrocyte has a lifespan of about 120 days while an erythrocyte in a sickle cell patient has an average lifespan of 12–15 days. Listed below are some of the conditions that may put a patient at risk of developing aplastic crisis if there is a disruption in erythropoiesis.
*
Hemolytic disorders -
hereditary spherocytosis
Hereditary spherocytosis (HS) is a congenital hemolytic disorder wherein a genetic genetic mutation, mutation coding for a structural membrane protein phenotype causes the red blood cells to be sphere-shaped (spherocytosis), rather than the norma ...
*
Hemoglobinopathies. -
sickle cell disease
Sickle cell disease (SCD), also simply called sickle cell, is a group of inherited Hemoglobinopathy, haemoglobin-related blood disorders. The most common type is known as sickle cell anemia. Sickle cell anemia results in an abnormality in the ...
,
thalassemia
Thalassemias are a group of Genetic disorder, inherited blood disorders that manifest as the production of reduced hemoglobin. Symptoms depend on the type of thalassemia and can vary from none to severe, including death. Often there is mild to ...
s
* Red cell enzymopathies -
G6PD Deficiency,
PK Deficiency
*
Autoimmune hemolytic anemias
* Chronic anemias, blood loss- low baseline production e.g.
iron deficiency anemia
Iron-deficiency anemia is anemia caused by a lack of iron. Anemia is defined as a decrease in the number of red blood cells or the amount of hemoglobin in the blood. When onset is slow, symptoms are often vague such as feeling tired, weak, sh ...
Parvovirus B19 Infection and Transient Aplastic Crisis
The majority of TAC are triggered by Parvovirus B19 in patients with hematologic disorders. These patients often present with high viral titers during profound anemia and are found to have reticulocytopenia upon further evaluation. Children are more affected than adults, and immunity appears to last several years after infection.
Patients with TAC due to Parvovirus B19 are less likely to have the typical slapped-cheek rash (
erythema infectiosum) characteristic of this infection. Infections with
Salmonella
''Salmonella'' is a genus of bacillus (shape), rod-shaped, (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two known species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' ...
,
S. pneumoniae, and other pathogens may also lead to TAC. With Parvovirus infection, bone marrow recovery typically occurs within 10 days and erythropoiesis resumes.
Parvovirus IgG/IgM may be obtained to assess for active infection. Patients may require IVIG or replacement of blood products during this transient bone marrow failure to reduce the chance of serious complications from the severe anemia.
See also
*
Erythropoiesis
Erythropoiesis (from Greek ''erythro'', meaning ''red'' and ''poiesis'', meaning ''to make'') is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.
It is s ...
– process of creating red blood cells
*
Hemolytic anemia
Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonl ...
– reduced number of red blood cells due to destruction of the cells after they were made
*
Nutritional anemia – reduced number of red blood cells due to vitamin deficiency or other dietary factors
*
Spherocytosis- the shape of red blood cell becomes spherical than bi-concave.
References
External links
{{Diseases of RBCs
Red blood cell disorders