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Thrombocytopenia

  • Lower than normal number of platelets, the blood cells responsible for clotting
  • Symptoms include bleeding gums, nosebleeds, bruising easily, heavy menstrual blood flow
  • Treatment includes medication, surgery, platelet transfusion, plasma exchange
  • Involves Hematology, Pediatric Hematology & Oncology

Thrombocytopenia

Overview

Thrombocytopenia is a condition in which a person has a low number of platelets, the blood cells responsible for clotting. Platelets help form clots or plugs to stop wounds from bleeding. People with severe thrombocytopenia may bleed easily and have difficulty stopping the bleeding. However, those with mild thrombocytopenia may have no issues with excessive bleeding.

There are mild and severe forms of thrombocytopenia. The mild forms are not urgent and rarely cause abnormal bleeding. In contrast, severe forms are life-threatening, causing gastrointestinal bleeding, heavy menstruation or brain hemorrhages (bleeding within the brain).

Thrombocytopenia has different causes. Sometimes, the bone marrow isn’t producing enough platelets, or the platelets are being removed from the bloodstream by the immune system, spleen, or liver. Determining the cause of thrombocytopenia helps doctors determine how to treat the condition.

A commonly diagnosed cause of thrombocytopenia, called immune thrombocytopenic purpura (ITP), is an autoimmune condition that can be temporary (called acute ITP), or last a long time (called chronic ITP). In children, acute ITP is more common than chronic ITP, and it often follows a viral infection, medication, or vaccination. In adults, chronic ITP is more common and often requires medical treatment.

“Different treatments are available to manage the different causes of thrombocytopenia,” says Mary Jane Hogan, MD, MPH, a Yale Medicine pediatric hematologist and oncologist. “It is important to determine the cause of thrombocytopenia in order to receive the best treatment to prevent excessive bleeding.”

What is thrombocytopenia?

Thrombocytopenia is a condition that lowers the body’s platelet count, sometimes making it more difficult for the blood to clot after an injury.

Another name for platelets is thrombocytes. Cytopenia is the term used to refer to a lower-than-normal percentage of blood cells. Thus, thrombocytopenia, describes a lower than normal platelet count.

In healthy people, the blood contains between 150,000 and 450,000 platelets per microliter of blood. Excessive bleeding due to thrombocytopenia becomes more noticeable as platelet counts drop.

There are three levels of thrombocytopenia resulting in different degrees of clinical severity:

  • Mild thrombocytopenia. When platelet levels are between 100,000 and 150,000 platelets per microliter, there is typically no increased risk of bleeding.
  • Moderate thrombocytopenia. When platelet levels are between 50,000 and 99,999 platelets per microliter, there also is typically no increased risk of bleeding.
  • Severe thrombocytopenia. When platelet levels drop below 50,000 platelets per microliter, there is an increased risk of bleeding. When platelet counts are below 10,000 platelets per microliter, there is a high risk of life-threatening bleeding.

What causes thrombocytopenia?

Thrombocytopenia can occur because the bone marrow doesn’t produce enough platelets, and there are different reasons for this. Certain medications, chemotherapy (medication to treat cancer), radiation therapy, infections, poor nutrition, or inherited genetic conditions can cause the bone marrow to stop making platelets. Certain cancers can also arise in the marrow, such as leukemia (a cancer of the white blood cells), or cancers can infiltrate into the marrow, such as solid tumors (metastases), which cause the marrow to stop making platelets. Certain metabolic disorders can also cause abnormal proteins or fats to infiltrate into the marrow causing it to stop making platelets.

Thrombocytopenia can also occur because platelets are being removed from the bloodstream by the immune system, spleen, or liver. Common causes include infections, medications, an autoimmune disease, inherited or acquired bleeding disorders, an enlarged spleen for any reason, liver disease, or an inherited immune deficiency or disorder.

Thrombocytopenia is often caused by medical conditions or certain medications. A family history of the condition may also be a factor.

Some of the medical conditions that are associated with thrombocytopenia include:

  • Bone marrow disorders, such as aplastic anemia or myelodysplastic syndrome
  • Leukemia or other bone marrow cancer
  • An infection of the bone marrow
  • A viral infection
  • Liver cirrhosis
  • Hepatitis C
  • HIV
  • Bacterial sepsis
  • Lupus, scleroderma, or other autoimmune diseases
  • Pregnancy
  • Folate deficiency
  • Vitamin B12 or other nutrient deficiencies
  • Alcohol use disorder
  • An enlarged spleen
  • Gaucher disease and other metabolic disorders
  • Disseminated intravascular coagulation (DIC), a blood clotting disorder
  • Metastatic cancer
  • COVID-19

Some medications or chemicals that can cause thrombocytopenia include:

  • Chemotherapy for cancer
  • Radiation therapy for cancer
  • Drugs, such as cyclosporine, that suppress the immune system after organ transplantation
  • Some diuretics, like furosemide
  • Blood thinners, including heparin
  • H2 blockers (which work by reducing the amount of acid produced and secreted by cells in the lining of the stomach) for acid reflux, including ranitidine and cimetidine
  • Some antibiotics, including penicillin and ampicillin
  • Sulfonamides
  • Certain anti-seizure medications, including valproic acid
  • Certain vaccines, including measles-mumps-rubella (MMR) and COVID-19
  • Some statins, which lower cholesterol
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Gold salts for arthritis
  • Quinine for malaria
  • Smoking tobacco

What are the symptoms of thrombocytopenia?

Some people with mild and moderate thrombocytopenia do not have any symptoms. Some people with severe thrombocytopenia may experience:

  • Bleeding gums or other areas in the mouth
  • Nosebleeds
  • Bruising easily
  • Heavy menstrual blood flow
  • Blood in the urine, stool, mucus, and/or vomit
  • Petechiae, a rash with flat, pin-sized red spots caused by bleeding beneath the skin
  • Purpura, a solid purple-red rash caused by bleeding under the skin
  • Bleeding in the brain due to injury

How is thrombocytopenia diagnosed?

A medical history, physical exam, and diagnostic blood testing help to discover thrombocytopenia. Additional testing is needed to diagnose the cause of thrombocytopenia to prevent and treat bleeding complications.

During the medical history part of the doctor visit, tell your doctor about new and old symptoms and how long you have had them. Mention any new drugs you’ve taken, the foods you eat, or new health conditions you’ve been diagnosed with. Tell your doctor if you have a family history of thrombocytopenia or bleeding disorders.

During a physical exam, a doctor should closely examine your skin, nose, and mouth for signs of bleeding, including reddish pin-sized spots on the skin (petechiae) or splotches of reddish-purple (purpura). They may also feel for enlarged lymph nodes in your neck, armpits, and groin as well as your abdomen to check for an enlarged spleen, liver, or mass.

You may need one or more of the following diagnostic tests:

  • Blood tests, including a complete blood count (CBC), which check to see if red blood cells, white blood cells, and platelets are normal in number, and a blood smear, during which the blood (including the platelets) is examined under a microscope for abnormal shapes. Other blood tests look for clotting proteins, chemistries, types of infections, and immune function markers.
  • Bone marrow tests, including aspiration (in which a small sample of bone marrow liquid is removed via a thin needle for analysis) and a biopsy (in which a small sample of bone marrow tissue is removed, using a thicker needle, for analysis). These marrow samples are used to determine if the bone marrow is healthy and producing the correct amount of blood cells, including platelets, using a variety of specialized techniques.
  • Imaging tests, like a computed tomography (CT) scan or a magnetic resonance imaging (MRI) scan of the body, to check for an enlarged spleen or liver abnormalities, tumors, or signs of bleeding.

How is thrombocytopenia treated?

Because different conditions can cause thrombocytopenia, treatment depends on the cause of the condition. When another health condition causes thrombocytopenia, for example, treating the underlying issue should help platelet levels to rise. Or, if the condition arises as a side effect of a particular medication, switching to another one should improve the situation. When a different health or genetic condition is not the cause of thrombocytopenia, then the thrombocytopenia is often labelled “immune thrombocytopenia purpura” or ITP.

In general, immune thrombocytopenia purpura treatments include:

  • Corticosteroids, such as prednisone or dexamethasone, may be an effective first-line treatment
  • Immunoglobulin therapy (IVIG), an intravenous therapy
  • Thrombopoietin receptor agonists, which help to stimulate platelet production
  • Rituximab, an immune suppressor, may help to improve platelet levels in patients who don’t respond to the above therapies.
  • Splenectomy, or surgical removal of the spleen, if immune modulation therapies in addition to the above therapies fail

In general, supportive care to stop bleeding from any cause of thrombocytopenia includes:

  • Aminocaproic acid or transexamic acid, which promotes clotting in the mucosa (a mucus membrane that lines certain cavities in the body), such as in the nose, mouth, gastrointestinal, or genitourinary tracts, may be given to patients experiencing life-threatening bleeding
  • Platelet transfusion is given when a patient with reduced platelet production is experiencing bleeding. Patients undergoing surgery may need platelet transfusions before and after the procedure to lower the risk of bleeding.
  • Plasma exchange is often used for patients with bleeding caused by thrombotic thrombocytic purpura (TTP), a rare, life-threatening type of thrombocytopenia.

What is the outlook for people with thrombocytopenia?

The prognosis for people with thrombocytopenia varies, depending on its severity and cause. People with mild thrombocytopenia may never experience bleeding or other complications. However, those with severe thrombocytopenia may be at risk of life-threatening complications, such as bleeding in the gastrointestinal system or the brain or spontaneous hemorrhage. Pregnant women with immune thrombocytopenic purpura may have an increased risk of bleeding complications during pregnancy.

Most Children who experience acute immune thrombocytopenia purpura typically recover fully. Most adults with immune thrombocytopenia purpura improve with treatment.

What makes Yale's approach to treating thrombocytopenia unique?

The Yale Pediatric and Adult Hematology Oncology programs offer sub-specialized physicians, nurse practitioners, nurses, and social workers who provide state-of-the-art care in the diagnosis of the different causes of thrombocytopenia and the necessary treatments for neonates, children, adolescents, and adults,” says Dr. Hogan. “In addition, some of our patients with thrombocytopenia have defective platelet function and are cared for by staff in our specialized Pediatric and Adult Hemostasis clinics.”