Rheumatoid Arthritis and Platelet Disorders

Causes of Thrombocytosis and Thrombocytopenia

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Activated platelets, artwork
Artist representation of a platelet among red blood cells.

Science Photo Library/Getty Images

Platelets, also known as thrombocytes, are blood cells that bind together whenever a blood vessel is damaged and, by doing so, form a clot to prevent bleeding. If you have rheumatoid arthritis (RA), it is not uncommon to experience an increase in your platelet count due to the persistent inflammation triggered by the disease. The condition, referred to as thrombocytosis, is usually not inherently problematic and serves more as a marker of disease activity.

On occasion, as 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. Thrombocytopenia 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 and 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 poorly understood, 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.

Thrombocytosis is a common condition in people with RA, affecting as many as half at some stage of their 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 occurs less commonly with RA than with lupus, another autoimmune disease, and affects only around three 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, like methotrexate, can cause thrombocytopenia is anywhere from 3 percent to 10 percent of users, according to data from the U.S. Food and Drug Administration.

Symptoms

Any abnormal rise or fall in the platelet cell count can trigger symptoms ranging from overt (visible) or subclinical (non-visible).

Thrombocytosis

Mild to moderate thrombocytosis is common with rheumatoid arthritis. Symptoms are usually mild to non-existence and often only revealed in blood tests. Thrombocytosis tends to worsen in tandem with the severity of the 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. Long-term RA in and of itself increases the 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 platelet count.

Most healthy people will have a platelet count of between 150,000 and 400,000/mm3. Thrombocytosis is diagnosed when the count exceeds 400,000/mm3. Thrombocytopenia tends to cause symptoms when the count is below 50,000/m3.

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.

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 by 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, that 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.

Immune Thrombocytopenia

Immune thrombocytopenia will also tend 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 term used to describe the antibodies that your body normally makes to fight off infections. IVIG is immunoglobulin purified from the blood of healthy donors. The treatment 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 doctor may recommend a reduction in your dose. The drugs most commonly associated with this are methotrexate, Azulfidine (sulfasalazine), Simponi (golimumab), and Actemra (tocilizumab).

If the symptoms are especially severe or the platelet levels fail to recover with a dose reduction, the doctor may need to stop treatment and switch 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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