Rheumatoid Arthritis and Platelet Disorders

Causes of Thrombocytosis and Thrombocytopenia

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Platelets, also known as thrombocytes, are blood cells that bind together whenever a blood vessel is damaged to form a clot and prevent bleeding. If you have rheumatoid arthritis (RA), it's possible that, at some point, you may experience an increase in your platelet count because of the persistent inflammation the disease triggers. Increased platelet count is called thrombocytosis. This condition isn't inherently problematic and serves more as a marker of disease activity than as something that requires active treatment.

On occasion, because it's an autoimmune disease, RA can turn its immune defenses on itself and destroy the blood-clotting cells, leading a low platelet count known as thrombocytopenia. This is also commonly caused by the drugs used to treat RA. Since platelets are vital to the integrity of the circulatory system, the development of thrombocytopenia can cause significant, sometimes serious bleeding disorders.

Causes

Thrombocytosis and thrombocytopenia can both 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, 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).

Thrombocytosis is a common condition in people with RA, affecting as many as half at some stage of their disease. It's even more common in lupus, another autoimmune disease.

Thrombocytopenia

Sometimes, rheumatoid arthritis 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. Food and Drug Administration (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 non-existent. 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 of 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 doctor 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.

Diagnosis Platelet Counts
Normal 150,000-400,000/mm3
Thrombocytosis Above 400,000/mm3
Thrombocytopenia Below 150,000/mm3
Symptomatic thrombocytopenia Below 50,000/mm3

Differential Diagnoses

Your doctor 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:

The differential diagnoses for thrombocytopenia may include:

Treatment

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

For 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) that temper specific parts of the immune response
  • JAK inhibitors like Xeljanz (tofacitinib) that block inflammation from within cells

Effort should also be made to quit smoking, exercise regularly, and lose excess weight, all of which can reduce inflammation and keep your RA symptoms under control.

For 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.

NSAIDs may also be prescribed but are generally avoided in people with low platelet counts due to increased risk of bleeding.

If your platelet count doesn't recover with treatment or is especially severe, your doctor 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. 

For Drug-Induced Thrombocytopenia

If your RA medications are causing a drop in your platelet count, your doctor 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 doctor 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.

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