Rheumatoid Arthritis and Platelet Disorders

People with rheumatoid arthritis (RA) have a higher risk of the blood platelet disorders thrombocytosis and thrombocytopenia. Platelets, also known as thrombocytes, are blood cells that bind together whenever a blood vessel is damaged to form a clot and prevent bleeding.

Thrombocytosis, an increased platelet count, is caused by persistent inflammation in RA. It does not usually cause symptoms or require treatment. Thrombocytopenia, a low platelet count, can be caused by an immune response in RA or drugs used to treat it. It can cause significant, sometimes serious bleeding disorders.

This article discusses platelet disorders and rheumatoid arthritis. It explains the differences between thrombocytosis and thrombocytopenia, how they both relate to RA, and methods for diagnosis and treatment.

What Are Platelet Disorders?

Platelet disorders are conditions where the blood platelet count is either too high or too low, or the platelets aren't working properly.

Platelets are tiny blood cells that are made in the bone marrow that stick together to form a blood clot. Blood clots help seal a wound and stop or slow down bleeding.

Having too many platelets, known as thrombocytosis, can cause blood clots to form inside blood vessels, which can block blood flow. Too few platelets, known as thrombocytopenia, can make it difficult for blood to clot and lead to bleeding problems.

RA and Platelet Disorders

Rheumatoid arthritis can affect blood platelets and lead to platelet disorders in a few different ways. Both thrombocytosis and thrombocytopenia can be traced back to a malfunctioning of the immune system, though the latter condition may also be a complication of RA treatment.

Thrombocytosis

Rheumatoid arthritis is characterized by an immune system gone awry. For reasons still being researched, in this condition, the immune system will suddenly attack its own cells and tissues.

With RA, the joints are the primary targets of the assault, causing cellular damage while spurring chronic and often unrelenting inflammation. This triggers the bone marrow to produce more white blood cells and platelets, causing thrombocytosis.

Left unchecked, the inflammation can actually impair the bone marrow's ability to make red blood cells, causing anemia (iron deficiency).

Thrombocytopenia

Sometimes, RA can trigger the opposite effect—thrombocytopenia. In this rare condition, known as immune thrombocytopenia, platelets are destroyed by the immune system.

Immune thrombocytopenia affects 9.5 of every 100,000 people, according to the National Organization of Rare Diseases.

More commonly, thrombocytopenia is induced by the drugs used to treat RA, including methotrexate and other disease-modifying antirheumatic drugs (DMARDs). The drugs are myelosuppressive, meaning they suppress the bone marrow's ability to produce blood cells, including red blood cells, white blood cells, and platelets.

Some DMARDs can cause thrombocytopenia in anywhere from 3% to 10% of users, according to the U.S. FDA.

Symptoms

Any abnormal rise or fall in the platelet cell count can cause noticeable symptoms in some people. In other cases, the person may not experience any symptoms at all and will only learn of the abnormal levels if blood tests are performed for other reasons.

Thrombocytosis

Mild to moderate thrombocytosis is common with rheumatoid arthritis. Symptoms are usually mild to nonexistent. The condition tends to worsen in tandem with an increased severity of autoimmune inflammation.

It is rare for RA-associated thrombocytosis to cause severe complications. The one exception may be in older adults with cardiovascular disease in whom chronic thrombocytopenia may increase the risk of a stroke or heart attack. Note, however, that long-term RA in and of itself increases cardiovascular risk.

Thrombocytopenia

In people with RA, thrombocytopenia may be mild and cause few signs or symptoms. If the platelet count drops beneath a certain threshold, the inability to clot will manifest with increasingly obvious symptoms. In rare cases, the platelets may be so low that internal bleeding occurs.

Common signs and symptoms associated with thrombocytopenia include:

• Persistent fatigue
• Easy or excessive bruising
• Tiny reddish spots (petechiae), usually on the lower legs
• Prolonged bleeding from cuts
• Bleeding gums or nose
• Excessive bleeding after an injury, such as a fall
• Blood in urine or stools
• Heavy menstrual flows
• Pain or fullness in the left upper abdomen, associated with an enlarged spleen

Diagnosis

Platelet disorders are primarily diagnosed with a complete blood count (CBC). This is a blood test that assesses the overall composition of your blood as well as its individual components, including your platelets.

While the CBC can provide definitive evidence of a platelet abnormality, your healthcare provider may also perform blood tests known as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to measure the level of generalized inflammation in your body.

Differential Diagnoses

Your healthcare provider may explore other possible causes if your symptoms are unusual or severe. Depending on the suspected cause, the investigation may include a bone marrow biopsy, imaging tests, blood tests, or a blood culture.

The differential diagnoses for thrombocytosis may include:

• Polycythemia vera
• Iron deficiency
• Infections, such as tuberculosis
• Hemolytic anemia
• Pancreatitis
• Celiac disease
• Inflammatory bowel disease
• Internal bleeding

The differential diagnoses for thrombocytopenia may include:

• Other medications that suppress bone marrow
• Other autoimmune diseases, such as lupus
• Liver disease or alcoholism
• Malignant hypertension
• Myelodysplastic syndromes
• Sepsis

Treatment

The treatment of platelet disorders in people with RA can vary depending on the underlying cause.

Thrombocytosis

Thrombocytosis in people with RA typically requires no treatment and will usually improve once the underlying inflammation is controlled.

The medication options include those that directly reduce inflammation and others that temper the autoimmune response. These include:

• Anti-inflammatory drugs, including corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs)
• Disease-modifying antirheumatic drugs (DMARDs) like methotrexate, which temper the immune system as a whole
• Biologic response modifiers like Enbrel (etanercept) or Humira (adalimumab), which temper specific parts of the immune response
• JAK inhibitors like Xeljanz (tofacitinib) that block inflammation from within cells

Other ways to reduce inflammation and keep your RA symptoms under control without medication include quitting smoking, exercising regularly, and losing excess weight.

Immune Thrombocytopenia

Immune thrombocytopenia also tends to improve once the autoimmune response is brought under control. This may involve one or more DMARD, biologic, or JAK inhibitor drugs.

Corticosteroids like prednisone may be used to support therapy by directly reducing inflammation.

If your platelet count doesn't recover with treatment or is especially severe, your healthcare provider may recommend intravenous immunoglobulin (IVIG).

Immunoglobulin is another type of antibody that your body normally makes to fight off infections. With IVIG, immunoglobulin purified from the blood of healthy donors is delivered through an IV drip, usually for several hours a day for one to five days.

The advantage of IVIG is that it can raise your platelet count quickly, albeit temporarily. 

Drug-induced Thrombocytopenia

If your RA medications are causing a drop in your platelet count, your healthcare provider may recommend a reduction in your dose. The drugs most commonly associated with this are:

• Methotrexate
• Azulfidine (sulfasalazine)
• Simponi (golimumab)
• Actemra (tocilizumab)

If the symptoms are especially severe or platelet levels fail to recover with a dose reduction, your healthcare provider may stop treatment and switch you to another drug.

One of the more effective alternatives is the biologic drug Rituxan (rituximab), which tempers the immune response by targeting B-cells, the very cells that destroy platelets in the autoimmune assault.

Summary

Rheumatoid arthritis can increase your risk of blood platelet disorders. Having too many blood platelets (thrombocytosis) may be related to chronic inflammation in RA. Too few platelets (thrombocytopenia) can be due to the immune system attacking the blood platelets or medications used to treat RA. 

Thrombocytosis does not usually cause any symptoms or severe complications. However, it can increase blood clotting, putting older adults with thrombocytosis at an increased risk of heart attack or stroke. Thrombocytopenia, on the other hand, decreases your blood’s ability to clot. This can increase your risk for internal bleeding and cause persistent fatigue, excessive bruising, and heavy menstrual periods. 

Blood platelet disorders associated with rheumatoid arthritis often resolve once the underlying autoimmune disease is managed. Thrombocytopenia caused by RA drugs may require changing your medication. Blood platelet disorders are not associated with a shortened lifespan. However, RA reduces life expectancy by an average of seven years for men and three years for women.