Thrombocytopenia and cancer

ALSO KNOWN AS: Bleeding disorders

RELATED CONDITIONS: Anemia, pancytopenia, neutropenia, immune thrombocytopenia (ITP)

DEFINITION: Thrombocytopenia is any disorder in which the number of platelets (thrombocytes, or blood cells that facilitate clotting) is below average.

Risk factors: Patients receiving large doses of chemotherapy, sometimes referred to as dose-dense therapy or radiation therapy, are at risk of developing thrombocytopenia, as are patients with leukemias, myeloma, and lymphomas. Serious infections, sepsis, and autoimmune diseases can also cause thrombocytopenia. Some patients who received the COVID-19 vaccine have been shown to develop a rare condition called vaccine-induced immune thrombotic thrombocytopenia.

Etiology and the disease process: Platelets, small cells without a nucleus, are formed from hematopoietic stem cells that develop into megakaryocytes. Megakaryocyte formation is stimulated by the endogenous hormone thrombopoietin. Other hematopoietic growth factors, including interleukin-11 and interleukin-6, are involved in the production of megakaryocytes. Platelets are formed when the megakaryocyte shatters into small pieces. It takes approximately five days for a new platelet to differentiate and mature from a hematopoietic stem cell, which means that a patient receiving chemotherapy or radiation therapy can have a low number of platelets for days; platelets have a life span of only seven to ten days.

The role of platelets is to allow blood to clot normally. Clotting occurs when a platelet encounters and adheres to a rough or jagged edge of damaged tissue. Other platelets adhere to this platelet in the platelet aggregation process and plug formation. Finally, fibrin is released, forming a mesh that traps other platelets and completes the clot.

Chemotherapy and radiation therapy target rapidly dividing cancer cells and other rapidly dividing cells, including hematopoietic stem cells, and reduce the number of platelets available for clotting and maintaining normal blood consistency. Patients with thrombocytopenia can have severe bleeding because of routine blood draws, stiff toothbrushes, vigorous nose blowing, shaving, and ingestion of sharp foods, such as popcorn and peanuts. Under healthy circumstances, tiny ruptures in blood vessels are immediately repaired; when severe thrombocytopenia is present, this bleeding can go unchecked.

Incidence: The incidence of patients who are receiving chemotherapy or radiation therapy that develop thrombocytopenia varies with type of cancer and chemotherapy or radiation given. It can be as low as 9 percent in breast cancer patients but as high as 37 percent in patients with multiple myeloma. Thrombocytopenia makes a patient more susceptible to internal bleeding and stroke and may lead to anemia.

Symptoms: Symptoms of thrombocytopenia include unexplained bruises, nosebleeds, bleeding gums, prolonged bleeding from minor cuts and blood draws, pink or reddish urine, and black or bloody stools.

Screening and diagnosis: Thrombocytopenia is usually confirmed by a blood test. A normal platelet count is 150,000 to 450,000 per microliter of blood. Sometimes, a bone marrow biopsy is needed to determine the cause of the thrombocytopenia. At below 10,000 platelets per microliter, the patient is at severe risk for internal bleeding; at this level, thrombocytopenia is a life-threatening condition.

Besides measuring the number of platelets in circulation, platelet function tests also may be done. In the past, the primary test for platelet dysfunction was bleeding time, but this test has fallen out of favor as it is not very sensitive or precise. Normal bleeding time, which requires small, thin cuts on a patient’s forearm to assess, is generally three to nine-and-a-half minutes but can be affected by aspirin and by the skill of the laboratory technician. Other tests that may be done on a blood sample include prothrombin time, a measure of how long it takes blood to clot with the glycoprotein prothrombin, which normally is eleven to thirteen seconds. A partial prothrombin time test is usually done in conjunction with the prothrombin time to measure the function of several clotting factors. Other tests include platelet aggregation studies that measure the response of blood or platelet-rich blood to specific agents known to induce aggregation (clumping) of platelets.

Treatment and therapy: Mild thrombocytopenia may be left untreated or left to resolve with treatment of the underlying cause. Transfusions of platelets can be used to treat life-threatening thrombocytopenia. Most oncologists, however, prefer not to use transfusions excessively because of the small but inherent risks of infections and immune system complications. Transfusions often involve platelets from several volunteer donors. Patients who receive platelets pooled from several donors risk developing antibodies to the various proteins on the platelet membranes. If antibodies develop, the patient may no longer respond to transfusions. The risk of immune system reactions can be reduced if a patient who requires platelet transfusions can arrange to receive platelets from one specific donor, preferably a sibling. If antibodies develop from transfusions of pooled platelets, it may be critical for a patient to receive platelets only from a sibling. A recombinant version of the naturally occurring protein responsible for platelet growth and development was approved by the Food and Drug Administration. This product, a recombinant human interleukin-11 (oprelvekin, or Neumega), is administered as a subcutaneous injection and stimulates the bone marrow to produce more platelets. In the 2010s and 2020s, new treatments, including thrombopoietin receptor agonists such as eltrombopag, romiplostim, avatrombopag, and lusutrombopag have shown promise in increasing long-term blood platelet counts. These new therapies joined rituximab and fostamatinib as medications to treat patients with thrombocytopenia and indicated a move towards more patient-specific therapeutic agents. Several other therapies are undoing clinical trials.

Prognosis, prevention, and outcomes: Recombinant growth factors and platelet transfusions are standard care for treating severe thrombocytopenia at many cancer centers. Transfusion, in particular, can rapidly, that is, within hours in some cases, increase platelet counts. Left untreated, the patient is at risk for serious and possibly life-threatening internal bleeding and stroke. Because chemotherapy and radiation therapy carry a risk of thrombocytopenia, the only way to prevent thrombocytopenia is to delay or reduce the amount of chemotherapy or radiation therapy, which is not advised as it lessens the success of the treatments.

Bibliography

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