What Causes A Low Platelet Count (Thrombocytopenia)?

What Is Platelet Count?  

Platelets, also called thrombocytes, are small blood cells that cause blood to clot and stop bleeding when a blood vessel is damaged. The bone marrow makes platelets from stem cells. A platelet has a lifespan of only 7-10 days, after which it is removed by the spleen, resulting in the body needing to constantly replenish its platelet supply. Platelet count is measured as part of a routine blood test called the complete blood count (CBC), which also evaluates other types of blood cells (red and white blood cells). 

Platelet count is the number of platelets per microliter of blood (platelets/µL). A normal platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. A platelet count below 150,000 is referred to as thrombocytopenia (low platelets), while a count exceeding 450,000 is classified as thrombocytosis (high platelets).

Having too many platelets or too little platelets in your blood can cause problems. Maintaining the proper level of platelets is essential to prevent significant blood loss during injuries while minimizing the risk of dangerous blood clots that can occur with an excess of platelets.

Function of Platelets

The main function of platelets is to form blood clots and stop bleeding. When a blood vessel is damaged, platelets cluster at the injury site to form a plug —a process called hemostasis. Below is an overview of the platelet function to stop bleeding. 

• When a blood vessel is damaged, and bleeding occurs, platelets stick to the site of injury in a process called “adhesion.” The platelets then release chemical signals that attract more platelets to form a blood clot.

• Once primary hemostasis is complete, the body moves on to secondary hemostasis, which includes activating other clotting factors and leading to the creation of a stable fibrin clot.

In addition to their essential function in hemostasis, platelets also aid in tissue repair and healing through the release of growth factors. Additionally, platelets interact with immune cells to help fight infections. 

What Does A Low Platelet Count (Thrombocytopenia) Mean?  

A platelet count below 150,000 cells per microliter (µL) is referred to as thrombocytopenia. A reduced platelet count can affect your ability to clot blood. Thrombocytopenia can vary in severity, ranging from mild to severe. Individuals with mild cases may not experience any bleeding complications, while severe thrombocytopenia can result in life-threatening bleeding.  

What Are The Most Common Causes of a Low Platelet Count?

The easiest way to understand the causes of thrombocytopenia is to divide it into three main mechanisms. A low platelet count can be due to: 

1. Decreased production of platelets due to bone marrow disorders or viral infections. 

2. Increased destruction of platelets in blood circulation as a result of an autoimmune disorder, infection, or certain drugs. 

3. Increased platelet breakdown in the liver or spleen. This can be due to spleen malfunction, portal hypertension, cirrhosis, or other conditions causing spleen enlargement and congestion. 

Decreased Production of Platelets

Thrombocytopenia can develop if the bone marrow doesn’t make enough blood cells, including enough platelets. This can occur due to several health conditions, including: 

• Aplastic anemia: a disorder of the bone marrow resulting in the body’s inability to produce the necessary amount of cells. 

• Myelodysplastic syndrome: a dysfunctional production of platelets often caused by aging or chemo-radiation.

• HIV (human immunodeficiency virus), hepatitis B and C virus, Dengue, Parvovirus B19, and Epstein-Barr virus.

• Cancers, such as leukemias and lymphomas. 

• Certain medications, such as antibiotics, anticonvulsants, and NSAIDs, along with chemotherapy and radiation therapy.

• Nutritional deficiencies, such as iron, vitamin B12. and folate.

• Inherited thrombocytopenias, such as Fanconi anemia and dyskeratosis congenita.

Autoimmune Diseases

Autoimmune diseases are conditions in which the body’s immune system mistakenly attacks healthy body tissues. For example, in people with an autoimmune condition called immune thrombocytopenia purpura (ITP), also called idiopathic thrombocytopenic purpura, the immune system destroys platelets, resulting in a low platelet count. 

Other autoimmune disorders, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), and scleroderma, can also lead to thrombocytopenia. 

Post-Transfusion Purpura occurs after blood transfusions when the immune system forms antibodies against transfused platelets, leading to rapid destruction of both transfused and native platelets. 

Non-Immune Platelet Destruction

Platelets may also be destroyed due to excessive clot formation, mechanical damage, or endothelial cell injury.

Disseminated Intravascular Coagulation (DIC) is a widespread activation of clotting factors that will consume platelets (leading to significant clotting), resulting in a depletion of platelets, causing bleeding. DIC is caused by bacterial and viral infections, severe trauma, and burns, amongst other reasons.

Thrombotic thrombocytopenic purpura (TTP) is a rare, but life-threatening disorder in which blood clots form in small blood vessels, blocking blood flow to the organs and using up platelets. This can lead to an increased risk of bleeding. TTP can occur due to a faulty gene inherited from one’s parents. It can also be acquired as a result of another medical condition. TTP can be fatal without immediate treatment in the hospital.

Hemolytic uremic syndrome (HUS) is similar to TTP. It is caused by a gastrointestinal bacterial infection from E. coli, which leads to endothelial damage and platelet consumption.

HELLP Syndrome can occur in pregnancy, causing endothelial dysfunction and platelet destruction. The acronym HELLP correlates with symptom presentation: Hemolysis, Elevated Liver enzymes, and Low Platelets. 

Increased Platelet Sequestration

The spleen is responsible for the removal of platelets that are at the end of their lifecycle. Normally, about one-third of platelet mass stays in the spleen. However, there are conditions that can cause spleen enlargement and congestion, leading to increased platelet mass and reduced circulating platelets. 

These health conditions can include bleeding, chronic liver diseases, and pulmonary hypertension (high blood pressure in the lungs). 

Other Low Platelet Count Causes

Other potential causes of low platelets include:

• Metabolic disorders, including Gaucher disease

• COVID-19

• Metastatic cancer

Medications Side Effects

Drug-induced thrombocytopenia develops when certain medications prevent the body from making enough platelets or destroy platelets in the blood.

In people with drug-induced immune thrombocytopenia, the immune system makes antibodies that destroy platelets. Heparin-induced thrombocytopenia is one of the most common causes. 

In people with drug-induced non-immune thrombocytopenia, a medication prevents the bone marrow from making enough platelets. For example, chemotherapy drugs and an anti-seizure medicine called valproic acid.

Medicines that cause drug-induced thrombocytopenia include:

• Blood thinners such as heparin (Find a list of other common blood thinners)

• Antiepileptic drugs such as valproic acid

• Diuretics or water pills such as furosemide

• Arthritis treatments such as gold salts

• Nonsteroidal anti-inflammatory drugs (NSAIDs)

• H2 blockers such as cimetidine and ranitidine

• Antibiotics such as penicillin, ampicillin, sulfonamides, linezolid, and others

• Antiarrhythmic drugs such as quinidine

• Malaria medications such as quinine

• Cholesterol-lowering drugs called statins

• Immunosuppressants such as cyclosporine

• Chemotherapy and radiation therapy for cancer

• Certain vaccines such as measles, mumps, rubella (MMR) and COVID-19 vaccines

Lifestyle and Environmental Factors  

Excessive Alcohol Consumption  

Heavy drinking can cause a person to develop thrombocytopenia. In addition to a decrease in platelet count, excessive alcohol use can also alter the shape and function of platelets. In people with alcohol use disorder (alcoholism), the presence of a low platelet count increases the risk of serious alcohol withdrawal complications such as withdrawal seizures and delirium tremens (DTs).

Pregnancy

Pregnant women can develop mild thrombocytopenia due to increased blood volume. This typically resolves after delivery.

Symptoms of Thrombocytopenia  

Symptoms of low platelets (thrombocytopenia) may include:

• Purpura (large red-purple patches caused by bleeding under the skin)

• Petechiae (small pinpoint red-purple spots in the skin due to superficial bleeding, most commonly seen in the lower legs)

• Prolonged or excessive bleeding from cuts or post-surgical/dental procedures

• Easy bruising (ecchymosis)

• Bleeding gums, nose, and blood in the urine or stools

• Heavy menstrual flow

• Enlarged spleen

• Fatigue, dizziness, or lightheadedness

• Abnormal paleness of the skin or mucous membranes (the lining of the eyes or mouth)

Potential Complications 

Severe thrombocytopenia (platelet count below 10,000 per microliter) can lead to life-threatening internal bleeding, including bleeding in the gastrointestinal tract and urinary tract. Severe cases can lead to potentially fatal brain bleeds. 

How is Low Platelet Count (Thrombocytopenia) Diagnosed?

Medical Examinations and Tests  

Your doctor may suspect low platelets based on your symptoms, medical history, and physical exam. They can order a blood test to diagnose thrombocytopenia. Additional testing may be necessary to find out the underlying cause of thrombocytopenia and prevent or treat abnormal bleeding. This may include:

• Blood tests, such as D-dimer (blood clot test), blood smear, blood chemistries, and immune system markers.

• Imaging tests such as CAT scan (also called CT or computed tomography scan) and MRI (magnetic resonance imaging) scan to look for an enlarged spleen, liver disease, or signs of internal bleeding.

• Bone marrow tests (aspiration or biopsy) to obtain a sample of bone marrow for examination in the laboratory.

Blood Tests  

Your healthcare provider will be able to determine your platelet count by conducting a blood test. There are three levels of clinical severity of thrombocytopenia:

How Do You Fix Low Platelets?  

Treatment for thrombocytopenia is dependent on its underlying cause, severity, and risk of bleeding. For example, thrombocytopenia caused by another health condition usually improves when that condition is treated. Drug-induced thrombocytopenia improves when the medication is stopped and/or switched to a different medication. Note that medications that can further cause thrombocytopenia include NSAIDs, sulfonamides, and heparin. Patients should also be cautious about any activities that may result in bleeding. 

Medications

Medication treatment options for immune thrombocytopenic purpura (ITP) include:

• Corticosteroids

• Intravenous immunoglobulin therapy (IVIG) for a quick increase of platelet counts in severe cases.

• Thrombopoetin receptor agonists (TPO-RAs) to stimulate platelet production.  Examples include avatrombopag, eltrombopag, and lusutrombopag. 

• Rituximab, an immune system suppressor

• Splenectomy (surgical removal of the spleen, the organ that stores about one-third of the platelets in the body), which is done when other treatments fail.

For TTP, a plasma exchange, alongside steroids and rituximab, is necessary to remove autoantibodies and toxins. Hemolytic uremic syndrome may also require dialysis and increased fluid intake (via IV hydration).

For patients with DIC, platelet transfusion is necessary to stop severe bleeding.  It is important to provide supportive care as the underlying cause is being treated.

For any bone marrow failure leading to thrombocytopenia, bone marrow stimulation is the first-line treatment. 

For autoimmune conditions, healthcare providers may recommend immunosuppressive treatment and/or a bone marrow transplant in severe instances.

A splenectomy (the surgical procedure to remove the spleen) may be considered in the case of thrombocytopenia resulting from hypersplenism (overactive spleen).

It is important to avoid any NSAIDs and aspirin if there is mild thrombocytopenia. Drugs that promote blood clotting, such as tranexamic acid and aminocaproic acid, can be used to stop bleeding. 

Lifestyle Adjustments and Preventive Measures

In the case of inherited platelet disorders, prevention is not an option. However,  precautions and lifestyle adjustments can help decrease the risk of thrombocytopenia.  For example:

• Avoid contact sports and activities that can increase the chance of injuries.

• Use soft-bristle toothbrushes to prevent gum bleeding.

• Avoid heavy alcohol use.

• Avoid exposure to toxic chemicals. 

• Be aware of medications that can cause low platelets, including over-the-counter medications, including nonsteroidal anti-inflammatory medications such as ibuprofen.

• Regular follow-ups if at risk due to autoimmune or hematologic conditions.

• Get vaccinated to protect against viral infections that can cause thrombocytopenia.

When to Seek Medical Attention? 

If you are experiencing any of the following symptoms, it might be best to seek medical attention:

• Frequent and excessive nosebleeds or bleeding from the gums. 

• Heavy and prolonged menstrual bleeding not previously experienced.

• Blood in urine, stools, or bloody vomits. 

• Unexplained or excessive bruising and petechiae (tiny purple, red, or brown spots in the skin).

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