Pancytopenia

What is Pancytopenia?

Pancytopenia is a blood-related condition where all three types of blood cells (red blood cells, white blood cells, and platelets) are fewer than usual. In specific terms, if a woman has a hemoglobin value (the molecule in red blood cells that carries oxygen) less than 12 g/dL, or a man has less than 13 g/dL, they could have Pancytopenia. Additionally, it’s diagnosed when there are fewer than 150,000 platelets (which are necessary for blood clotting) per mcL, or less than 4000 white blood cells (which fight infection) per mL (or less than 1800 neutrophils, a type of white blood cells, per mL). It’s important to note that these numbers can vary depending on age, gender, race, and different health situations.

Leukopenia, a decrease in white blood cells, involves mainly neutropenia, or a decrease in neutrophils, since neutrophils make up the majority of white blood cells. Pancytopenia is not a disease itself, but a sign of other underlying health problems. Furthermore, it can be linked to various harmless and harmful health conditions. Pancytopenia could occur because the body isn’t producing enough cells, or because it’s destroying too many. If a person shows signs of Pancytopenia, it’s crucial to thoroughly check to discover the underlying cause.

What Causes Pancytopenia?

Pancytopenia, a condition where you have low counts of all three types of blood cells (red blood cells, white blood cells, and platelets), can generally stem from two main issues. The first type, called a central type, relates to problems with the creation, or production, of these cells. The other type is called a peripheral type, which is linked to increased destruction of these cells.

The central type of pancytopenia often happens because of nutritional deficiencies. For example, it might happen because of aplastic anemia, which is a condition where your bone marrow fails to produce enough new blood cells. This could happen with no known cause, due to an immune-related issue, because of infections (like those caused by certain viruses), as a result of exposure to certain drugs or chemotherapy agents, or if you are not eating enough or not absorbing nutrients properly due to disorders like anorexia or alcoholism.

Pancytopenia might also occur from diseases which invade and replace the bone marrow, such as certain types of blood cancers (like lymphoma or leukemia) and other disorders. In serious cases, cancers that have spread to the bone marrow can also cause this condition.

The peripheral type of pancytopenia is associated with autoimmune diseases (where your immune system mistakenly attacks your own body), such as systemic lupus erythematosus and rheumatoid arthritis, and conditions that cause an enlarged spleen, a condition called hypersplenism which can be seen in alcoholic liver cirrhosis, HIV, tuberculosis and malaria.

In the context of the ongoing Covid-19 pandemic, pancytopenia has been observed in some cases of severe SARS-CoV-2 infection. The virus has been found in the bone marrow, suggesting it may directly cause the condition.

Even after extensive testing, sometimes no cause is found for the low blood cell counts, in which case it is called idiopathic cytopenias of unknown significance.

All in all, pancytopenia can occur from a host of causes from conditions that decrease production of blood cells, like autoimmune disorders, certain medications, aplastic anemia and vitamin deficiencies; diseases that replace or infiltrate bone marrow, like acute leukemias, chronic leukemias, myeloproliferative neoplasms, myelodysplastic syndromes, multiple myeloma, metastatic cancer, and other non-malignant conditions; and conditions that increase destruction of blood cells such as those linked with excessive clotting, an enlarged spleen, infections or certain autoimmune disorders. Consumption of certain drugs such as nonsteroidal anti-inflammatory drugs, certain heart medications, antimicrobials, anti-epileptics, and others can also lead to pancytopenia.

Risk Factors and Frequency for Pancytopenia

Pancytopenia, or a shortage of all types of blood cells, can often appear in both children and adults in their 30s and 40s. More men appear to have it than women. Conditions like multiple myeloma and myelodysplastic syndrome more commonly affect older patients, while younger patients are more likely to have conditions like acute leukemia and parvovirus B19 infection.

In North America, the most often seen causes are other kinds of blood disorders, followed by aplastic anemia, megaloblastic anemia, and HIV infections.

The main causes of pancytopenia can often depend on where you live and cultural factors, especially for conditions like megaloblastic anemia. Gender doesn’t really play a role in who gets megaloblastic anemia, but it seems like it happens more often in the East, likely due to the higher infection rates and use of certain medications linked to pancytopenia in developing countries.

• In India, a 2013 study found the most common causes of pancytopenia were hypersplenism, infections, suppression of the bone marrow due to cancer, chemotherapy, drug toxicity or radiotherapy, and megaloblastic anemia.
• A different study in India found megaloblastic anemia to be the top cause, followed by aplastic anemia.
• In Mexico, myelodysplastic syndromes and megaloblastic anemia are the most common causes, followed by acute myeloblastic leukemia, acute lymphoblastic leukemia, hypersplenism, and aplastic anemia.
• In Turkey, megaloblastic anemia is the main cause, followed by acute myeloid leukemia and aplastic anemia.

Signs and Symptoms of Pancytopenia

: Pancytopenia, a condition where the body has fewer blood cells than normal, can show varying symptoms. These can range from no symptoms in mild cases to serious complications in severe cases. Patients may also show signs due to a decrease in certain types of blood cells. Symptoms can include:

• Shortness of breath, fatigue, and chest pain from anemia
• Frequent infections from leukopenia
• Bruising, small red dots on the skin (petechiae), and increased bleeding from thrombocytopenia
• Severe infections from severe neutropenia
• Loss of appetite, nausea, or lethargy among patients with underlying liver disease
• Pain in the upper left side of the abdomen among patients with splenic sequestration
• General symptoms linked to autoimmune disorders or malignancies

When assessing pancytopenia, a patient’s medical history is critical. The doctor will likely ask about symptoms of autoimmune conditions, cancer, recent infections, medications, chemotherapy, or radiation therapy. A patient’s nutritional status is also important. Sometimes, pancytopenia may be the only symptom of malabsorption. If family members have had aplastic anemia, this may also be relevant.

During a physical examination, the doctor may notice paleness, petechiae, ulcers, and rashes. Signs of underlying liver disease may be present in patients with cirrhosis. Patients with splenic sequestration may have an enlarged spleen. Swollen lymph nodes may be present in patients with infections and lymphoma. Doctors will carefully check for signs of nutritional deficiencies in patients with eating disorders and alcoholism. A neurological examination is important to identify coordination problems, such as a positive Romberg test and ataxia. These can suggest damage to the spinal cord due to vitamin B12 deficiency and macrocytic anemia.

Testing for Pancytopenia

To start figuring out why you might have pancytopenia (a condition where you have low counts of all three types of blood cells), your doctor will conduct a complete blood count as well as a reticulocyte count, which is a count of a certain type of red blood cell. These counts can help the doctor understand if the pancytopenia is the result of your body not producing enough blood cells. Based on the size of your red blood cells, this test can also suggest if you have a type of anemia called megaloblastic anemia.

Another part of this initial examination is a peripheral blood smear, a test that checks for abnormalities in your blood cells. Abnormalities can include blasts (immature white blood cells), leukocytes with unusual characteristics, and additional immature cells. The presence of these abnormal cells could hint towards certain conditions. To further explore the causes, your doctor could recommend:

• Getting a sample from your bone marrow for testing (aspirate and biopsy)
• Genetic testing of your bone marrow or blood cells
• A technique called flow cytometry to further scrutinize the blood cells
• Molecular studies such as mutation analysis or gene expression profiling
• Checking your vitamin B12 and folate levels, liver function, and lactate dehydrogenase (an enzyme found in many body tissues)

Your doctor might look into the possibility of infections such as HIV, malaria, and tuberculosis since these infections can be associated with low blood cell count. If pancytopenia is related to a recent viral infection, usually the condition improves rapidly on its own without further check-ups.

Pancytopenia can also result from severe infections and result in a severe condition called sepsis. In these cases, further testing usually isn’t performed as the condition is most likely due to the sepsis itself. Once the infection or sepsis ends, the number of blood cells should increase back to normal levels.

Your doctor may suspect that certain diseases like hepatitis, autoimmune diseases or cancer might be the cause, so further tests might be needed. Sometimes, high levels of calcium and parathyroid hormone can cause pancytopenia, so these levels will be checked as well. In addition, your doctor might test your thyroid since an overactive thyroid can be linked with pancytopenia.

If no clear cause is found, a procedure to get a bone marrow sample (aspiration and biopsy) might be recommended. This can largely help in deciding if it is pancytopenia. Common revelations from this test are an underproduction of new blood cells within the marrow, megaloblastic anemia and cancers related to blood cells. From the bone marrow sample, a pathological examination could help spot cancerous etiologies. It can reveal cancerous cells, primary or secondary cancer cells or cells relating to fibroblasts, granulomas from tuberculosis, sarcoidosis, or fungal infections.

The doctor will also be looking for specific evidence of the diseases causing your pancytopenia, such as types of abnormal cells associated with conditions like acute leukemias, hairy cell leukemia, myelodysplastic syndromes, myeloproliferative neoplasm, or deficiencies of folate and/or vitamin B12, which could indicate myelofibrosis or other tumors. Other signs can include red blood cell deformation or damage indicating coagulation disorders and potential cancerous invasion.

Treatment Options for Pancytopenia

The treatment for pancytopenia, a condition where a person has low counts of red and white blood cells and platelets, depends on the underlying cause. This can often be linked to nutritional deficiencies, certain medications, infections or autoimmune conditions, and even cancer.

For example, if a lack of certain nutrients has led to the condition, these will be reintroduced into the patient’s diet. Alternatively, if a specific drug appears to be at fault, this will be stopped. Medical treatment is also necessary if a patient is diagnosed with infections, such as HIV or tuberculosis, or an autoimmune condition or malignancy (cancer).

Sometimes, viral infections might lead to a temporary form of pancytopenia known as aplastic anemia. In such cases, treatment mainly involves managing the symptoms until the body recovers on its own.

For severe cases of aplastic anemia, treatment could include a hematopoietic stem cell transplant or procedures that suppress the immune system’s abnormal response. These patients would usually be referred to a hematologist, a doctor specializing in blood disorders.

Supportive care includes giving patients a blood transfusion to replace the missing red blood cells and relieve symptoms, ensuring sufficient oxygen is supplied to the body’s vital organs. Platelets, cells that help blood clot, could also be transfused when their levels drop to less than 10,000 per mcL. This is done to prevent spontaneous bleeding in the brain.

Patients with extremely low white blood cell counts (less than 500 per ml), specifically a type known as neutrophils, are at increased risk of life-threatening infections. These patients are often prescribed broad-spectrum antibiotics to protect them against a variety of bacteria and other harmful microorganisms. In most cases, the antibiotics would be started at the first sign of a fever.

What else can Pancytopenia be?

When someone exhibits pancytopenia, which is a condition where the body has lower levels of red and white blood cells and platelets, a thorough assessment is typically conducted to determine its cause. Various illnesses could manifest pancytopenia, and these include disorders that affect the bone marrow and some that do not.

Conditions related to the bone marrow that could cause pancytopenia include:

• Aplastic anemia: a rare condition where the body stops producting enough new blood cells
• Myelodysplastic syndrome: a group of disorders caused by poorly formed blood cells or cells that don’t work correctly
• Acute leukemia: a form of blood and bone marrow cancer that produces excessive immature blood cells
• Myelofibrosis: a serious bone marrow disorder that disrupts the body’s normal production of blood cells
• Megaloblastic anemia: a condition caused by a deficiency of either vitamin B12 or folate
• Paroxysmal nocturnal hemoglobinuria: a rare acquired, life-threatening disease of the blood
• Fanconi anemia: a rare genetic disease that affects the bone marrow and results in decreased production of all types of blood cells

The most common inherited cause of bone marrow failure leading to pancytopenia is Fanconi anemia. In cases of myelofibrosis, the bone marrow cells are replaced by fibrous tissue.

Certain malignancies such as lymphoma, multiple myeloma, and hairy cell leukemia may also lead to pancytopenia. In addition, several non-bone marrow related conditions can cause pancytopenia and these include systemic lupus erythematosus (a long-term autoimmune disease) and a range of infections such as parvovirus B19, Epstein Barr virus, HIV, hepatitis, leishmaniasis, tuberculosis, malaria, and histoplasmosis.

What to expect with Pancytopenia

The outlook for pancytopenia, a condition where the body has low levels of certain blood cells, largely depends on the cause behind it. For instances where it’s caused by viral infections, the outlook is great because your body usually gets better on its own without requiring treatment.

In people with a blood disorder called myelodysplastic syndrome, the outlook depends on the severity of pancytopenia and how much of an immature type of blood cell, called blasts, are found in the bone marrow.

Patients undergoing certain treatments like chemotherapy or consuming specific drugs that can cause pancytopenia (such as methotrexate, linezolid, or anticonvulsants) may need to stop taking the medication if there are suitable alternatives.

Most of the time, pancytopenia can be reversed when the treatment causing it is stopped.

Possible Complications When Diagnosed with Pancytopenia

People with pancytopenia, a condition characterized by low counts of red and white blood cells and platelets, are more susceptible to getting infections, severe anemia which can be life-threatening, and uncontrolled bleeding. If these patients show symptoms of fever, doctors typically prescribe a wide range of antibiotics and antifungal medications to fight against infection. Immediate transfusions of red blood cells and platelets may be required if the patient is experiencing severe anemia or bleeding due to low platelet count.

In addition, severe conditions like tumor lysis syndrome can occur in patients who are undergoing chemotherapy for large tumors, for instance, in cases of high-grade lymphoma and acute leukemia.

Common complications include:

• Infections
• Life-threatening anemia
• Bleeding
• Tumor lysis syndrome in patients receiving chemotherapy

Preventing Pancytopenia

Patients need to be informed about the possible side effects and harmful impacts from both prescribed medications and supplements bought over the counter. If a patient is prescribed certain drugs like methotrexate or linezolid, it’s important that they understand the need for regular check-ups and blood tests. In addition, patients who have blood-related cancers (such as multiple myeloma, a bone marrow cancer; myelodysplastic syndrome, a group of disorders that cause a drop in blood cells; lymphoma, or acute leukemias, a fast-growing blood and bone marrow cancer) should be warned about the potential for pancytopenia.

Pancytopenia is a medical condition where a person has low levels of red and white blood cells and platelets. If a patient is diagnosed with pancytopenia, they should be aware of the complications this condition can cause such as an increased risk for infections, bleeding, and signs of anemia like fatigue or weakness. Patients should also be warned against taking other medications that might worsen pancytopenia.