What is Secondary Thrombocytosis?
Platelets, also known as “blood dust,” are part of our blood that is made in the bone marrow and play an essential role in forming blood clots. A typical platelet count in adults and children usually falls between 150,000 and 450,000 per microliter (μL) of blood, but this can vary depending on the clinical laboratory. The condition called thrombocytosis, or thrombocythemia, happens when the platelet count rises above 450,000/μL of blood.
Thrombocytosis can be split into two types called primary and secondary (or reactive) thrombocytosis, and knowing the difference between these two types is important because it influences how the condition is evaluated, its outlook, and how it’s treated. Primary thrombocytosis is when the bone marrow cells that make platelets produce too many, and it is usually linked to diseases where the bone marrow produces too many blood cells, known as myeloproliferative neoplasms. This type of thrombocytosis, particularly when it comes with conditions like essential thrombocythemia and polycythemia vera, carries a higher risk of clotting and bleeding compared to secondary thrombocytosis.
Secondary thrombocytosis, also known as reactive thrombocytosis, features an unusually high platelet count due to other events, illnesses, or medications. This type of thrombocytosis, which is more common than primary thrombocytosis, is typically spotted through standard lab tests. Usually, symptoms are because of an underlying issue rather than the high platelet count itself. However, in rare cases, extremely high platelet counts can lead to clotting events like heart attacks, blockages in the intestine’s veins, and blood clots in the lungs.
While secondary thrombocytosis is generally harmless, the root causes, which can include cancer, connective tissue diseases, and persistent infections, might be linked to a higher likelihood of negative health outcomes. Typically, 80% to 90% of people with high platelet counts have secondary thrombocytosis. This condition can be caused by temporary issues like acute blood loss or infection, as well as long-term factors like iron deficiency, having no spleen, cancer, chronic inflammation, or infectious diseases. Reactive thrombocytosis usually goes away once the underlying cause is taken care of.
What Causes Secondary Thrombocytosis?
Secondary thrombocytosis –a condition where there are too many platelets in the blood– is often caused by inflammation in the body. It can occur due to a variety of reasons such as inflammation, decreased oxygen supply, infection, heart attack, and lack of iron.
For example, if you have an infection, whether it’s a regular bacterial or viral one or a chronic condition like tuberculosis, you can experience secondary thrombocytosis. This happens because infections can increase the production of IL6, a substance that encourages the generation of thrombopoietin, which then leads to increased platelet production. Signs of infection, like fever, rapid heart rate, weight loss, anemia, white blood cell increase and low albumin may indicate this condition. An interesting fact is that COVID-19 usually doesn’t lead to an increase in platelets; often, it’s the opposite. Inflammation caused by COVID-19 generates large amounts of inflammatory substances, including IL6, and causes an increase in platelet production.
Having your spleen removed – due to a range of reasons, including certain diseases or injuries – can also cause thrombocytosis. This happens because the spleen normally helps modulate platelet count; without it, platelets can increase. A significant increase in platelet count can also occur when the spleen isn’t working effectively. The risk of blood clotting can increase after a spleen removal. Doctors may recommend specific treatments to reduce platelets or vaccination to bolster the immune system and prevent infections.
Iron deficiency can cause an increase in platelet count. This condition will often get better on its own once the body’s iron levels are back to normal. If not, there may be another cause behind the high platelet count. Iron deficiency can also lead to a type of von Willebrand disease, a bleeding disorder when platelet counts are very high.
Some medications can increase platelets by causing the release of IL6. Many different types of drugs can cause this, including beta-lactam antibiotics, gemcitabine, and clozapine. Once the medication is stopped, the platelet count usually goes back to normal.
Just as with infections, inflammatory conditions – such as rheumatoid arthritis, celiac disease, polyarteritis nodosa, and giant cell arteritis – can cause an increase in platelets. Similarly, allergies and chronic inflammation can lead to a rise in platelet count.
Interestingly, diseases that break down or destroy red blood cells, such as cold agglutinin disease (CAD), can also raise platelet count. In these cases, blood thinning medications are often recommended to prevent clots.
Cancer, particularly cancers that have spread or lymphoma, can cause elevated platelets. Sometimes, the treatment for cancer can also increase platelets.
Lastly, even exercise routines can impact the platelet count. Whilst single episodes of intense exercise can transiently increase the platelet count, regular exercise reduces platelet stickiness and clumping, thereby reducing the risk of blood clots.
Risk Factors and Frequency for Secondary Thrombocytosis
Secondary thrombocytosis, which is a condition characterized by too many platelets in the blood, is more common than primary thrombocytosis. In fact, about 75% of people who don’t have other blood disorders will develop this condition after having their spleen removed. Also, in those dealing with iron deficiency anemia, about 30% may develop what’s known as reactive thrombocytosis.
Some interesting data has emerged from different studies. One from China showed that about a quarter of kids with respiratory infections had an unusually high platelet count. Another in Italy found that half of the hospitalized children aged 1 to 24 months who had caught infections from their community ended up developing thrombocytosis.
Usually, preterm babies are born with fewer platelets, while full-term and late preterm babies often see a spike in platelets right after birth, which then decreases in the first month. It’s also common for kids with high platelet counts to have respiratory infections, and sometimes, autoimmune diseases.
It’s important to note that no specific race, sex or age group has been found to have a higher likelihood of getting secondary thrombocytosis.
Signs and Symptoms of Secondary Thrombocytosis
Secondary thrombocytosis, or a high number of platelets in the blood, usually doesn’t cause symptoms on its own. However, if you do have symptoms, it’s likely because of the underlying issue that’s causing the platelet increase. Doctors will want to check if you have recently had trauma or surgery, are showing signs of infection or inflammation, have a history of bleeding, have vascular diseases, or are using certain medications. Other lifestyle factors like smoking and alcohol consumption may also be investigated.
- Recent trauma or surgery
- Removal of the spleen or high rate of red blood cell destruction
- Signs of infection or cancer (fever, sweats, weight loss, and fatigue)
- History of excessive bleeding (heavy menstrual bleeding or gastrointestinal bleeding), lack of iron, or long-term blood disorder
- History of blood clot in an artery or vein
- Use of certain medications
- Smoking and alcohol drinking patterns
During the physical examination, the doctor will look out for signs like bleeding or bruising on the skin or mucous membranes, enlarged lymph nodes, enlarged liver or spleen, and signs of arterial or venous thrombosis, which is the formation of a blood clot inside a blood vessel.
- Bruising or bleeding on the skin or inside the mouth
- Enlarged lymph nodes
- Enlarged liver or spleen
- Signs of blood clot in an artery or vein
Testing for Secondary Thrombocytosis
Thrombocytosis, or thrombocythemia, is a condition that can be identified by a blood test that shows a platelet count greater than 450,000 per microliter. Platelets are small blood cells that help your body form clots to stop bleeding. If you have thrombocytosis, it means that you have too many platelets in your blood.
Your doctor may order additional tests to determine whether this condition is primary or secondary in nature. ‘Primary’ suggests that the issue has to do with your bone marrow producing too many platelets without a clear reason. On the other hand, ‘secondary’ implies that the excess of platelets is a reaction to another illness or condition.
In order to identify the cause behind the excessive platelets, your doctor may recommend the following tests:
- Peripheral blood smear – This test gives a closer look at the different types of cells in your blood.
- Erythrocyte sedimentation rate and C-reactive protein – These tests measure inflammation in your body.
- Antinuclear antibody and rheumatoid factor – These tests can help determine if an autoimmune disorder is responsible.
- Iron studies (eg, serum iron, total iron-binding capacity, and serum ferritin) – These tests can detect whether you have too much or too little iron in your body.
If these tests still do not provide a clear diagnosis, additional investigations like genetic testing and even a bone marrow biopsy may be considered to clearly pinpoint whether the high platelet count is primary or secondary.
Treatment Options for Secondary Thrombocytosis
Secondary thrombocytosis is when the body produces too many platelets, a type of blood cell that helps with clotting. It often resolves once the underlying medical issue causing the high platelet levels is treated. For instance, if secondary thrombocytosis is due to iron deficiency in patients with inflammatory bowel disease, supplementing iron can restore platelet counts to normal levels.
Treatments intended to lower platelet count, like aspirin, are generally not required for secondary thrombocytosis because there’s a very low risk of developing blood clots. However, patients with very high platelet counts, or those who have had, or are at risk of, complications from high platelet counts, may be considered for antithrombotic therapy. This is a treatment that helps prevent blood clots.
Plateletpheresis, a procedure that physically removes platelets from the blood, might be an option for patients with signs of clotting or active bleeding. This treatment offers a quick, but temporary, reduction in platelet counts.
What else can Secondary Thrombocytosis be?
When considering secondary thrombocytosis, a condition that prompts your body to produce too many platelets, several other potential diagnoses must also be considered:
- Essential thrombocythemia (a kind of genetic disorder that might run in families). The presence of certain markers like JAK2, CALB, and MPL are suggestive of this condition.
- Myelodysplastic syndrome, though this is rare.
- Polycythemia vera (a slow-growing blood cancer)
- Chronic myeloid leukemia (another type of blood cancer)
- Myelofibrosis (a serious bone marrow disorder)
- Spurious thrombocytosis, where non-platelet particles are mistakenly counted as platelets.
- Pseudothrombocytosis, which is similar to spurious thrombocytosis, where the platelet count appears falsely high due to certain diseases or substances.
Knowing about these other conditions can help in coming up with an accurate diagnosis.
What to expect with Secondary Thrombocytosis
Secondary thrombocytosis means that the number of platelets in your blood is higher than normal, but this condition is usually temporary and gets better when the root cause is treated. The long-term outlook depends on what’s causing the higher platelet count in the first place.
In some cases, like chronic obstructive pulmonary disease (which is a type of lung disease) or certain types of gastrointestinal cancers (like esophageal and colorectal cancer which affect your food pipe or large intestine respectively), having thrombocytosis could mean the overall condition is more serious.
Possible Complications When Diagnosed with Secondary Thrombocytosis
Complications from secondary thrombocytosis, a condition where the body makes too many blood platelets, are rarely seen. However, it’s important for doctors to know about the general complications of this condition, which include:
- Arterial and venous thrombosis, leading to stroke, heart attack, or a reduction in blood flow to the digestive organs. This risk increases when platelet counts go above 1,000,000/μL.
- Bleeding
- Spontaneous miscarriage
- Stillbirth or slowed growth of a baby in the womb
- Development of acute myeloid leukemia or primary myelofibrosis, which are blood and bone marrow diseases
Preventing Secondary Thrombocytosis
Patients should be told that even though a condition called secondary thrombocytosis is often discovered by chance, it’s crucial to treat the root cause. Thrombocytosis, which is an abnormally high number of platelets in the blood, can cause serious issues like blood clots if not managed properly. Additionally, patients should know that a variant of this condition, called reactive thrombocytosis, is a lab finding that gets better when the main cause is treated.
Because of this, following the doctor’s treatment plan and making sure to attend all follow-up appointments is extremely important for successful management of the condition.
