At the 2007 annual meeting of the Oncology Nursing Society (ONS), several aspects of managing thrombocytopenia were addressed, with a focus on chemotherapy-induced thrombocytopenia. In addition, novel treatment strategies for thrombocytopenia with differing underlying etiologies and external causative factors were discussed.  

Thrombocytopenia is defined as a platelet count of less than 150,000 microL.[1] Platelets, or thrombocytes, are large fragments from megakaryocytes and are vital for hemostatic activity as well as for maintaining capillary integrity.[2] Thrombocytopenia may occur through decreased production of platelets, abnormal distribution of platelets, and increased destruction of platelets (see Table 1). It is a common complication in patients with cancer, particularly those undergoing treatment with chemotherapy; however, there are several diseases and/or drugs that may result in thrombocytopenia. 

Table 1: Causes of Thrombocytopenia

The normal platelet range is 150,000–400,000 microL, and although thrombocytopenia is technically considered to be a platelet count of less than 150,000 microL, it is often not diagnosed until it is below 100,000 microL.¹ Presentation of thrombocytopenia, particularly among patients with more severe grades, may include bleeding, ecchymoses, petechiae, purpura, and hypersplenism.

Table 2: Grades of Thrombocytopenia

Healthcare providers with patients who present with any clinical presentations of thrombocytopenia should assess for bleeding, particularly in dependent areas of the body.  The ecchymotic areas can be marked with a pen to assess for an increase in bleeding.  If thrombocytopenia occurs without a clinical explanation, a peripheral smear can be obtained from the hematology laboratory to confirm the presence of thrombocytopenia.  A peripheral will confirm the diagnosis of thrombocytopenia and assess the size and distribution of platelets.  

In addition, a history and physical exam should include specific information such as:  

• Date of chemotherapy or prior chemotherapy treatment
• Transfusion history
• Recent viral or rickettsial infection
• Sepsis
• Recent travel
• Malignancy
• Nonhematologic diseases
• Family history
• Nutritional history
• Medication
• Pregnancy history
• Organ recipient

Chemotherapy-induced Thrombocytopenia 

The most common cause of thrombocytopenia is treatment with chemotherapy. Factors that place patients at a higher risk for developing chemotherapy-induced thrombocytopenia are the following:            

• Certain chemotherapy or targeted agents associated with higher rates of thrombocytopenia (See Tables 3)
• Bone marrow involvement of disease
• Specific types of cancers
• Treatment with radiation therapy
• Prior therapy for treatment of malignancy 

Table 3: Chemotherapy and Targeted Agents Associated with Increased Risk of Thrombocytopenia

At present, treatment for chemotherapy-induced thrombocytopenia may include oprelvekin, a megakaryocyte growth factor that stimulates proliferation of hematopoietic stem cells and megakaryocyte progenitors and induced megakaryocytic maturation. Oprelvekin was approved in 1998 for nonmyeloid malignancies. However, patients with a history of cardiac complications are not suitable candidates for oprelvekin, as it increases renal sodium retention, expands plasma volume, and increases intravascular fluid.  

Platelet transfusions are another option for the treatment of chemotherapy-induced thrombocytopenia. Platelet transfusions come with their own risks and patients may not respond to platelet transfusions.  

Decrease Response to Platelets  

• Refractory to platelet transfusion (platelet count response to two or more consecutive platelet transfusions that is significantly less than expected, the presence of alloimmunization, or transfusion responses that are <5000/microL)
• Alloimmunication
• Infection
• Splenomegaly
• Bleeding
• ABO mismatch
• DIC

Although patients with chemotherapy-induced thrombocytopenia have effective options for this side effect (oprelvekin and transfusions), the treatments both come with risks and potential diminished responses. Effective treatment of chemotherapy-induced thrombocytopenia among cancer patients is important as it may disrupt optimal schedule dosing. The future direction of treatment for chemotherapy-induced thrombocytopenia includes the use of thrombopoietins, such as recombinant thrombopoietins, TPO peptide mimetic and thrombopoietic fusion proteins, and platelet growth factors.  

Other Types of Thrombocytopenia  

Although chemotherapy is the most common cause of thrombocytopenia, it may also be the result of several other factors. Several types of thrombocytopenia, such as immune thrombocytopenia purpura (ITP) were also discussed at this year’s ONS meeting.  

Approximately 16,000 patients per year are diagnosed with ITP in the United States.[3] ITP is an immune-mediated disorder in which platelets are damaged by autoreactive antibodies and destroyed prematurely by the reticuloendothelial system. Patients with ITP usually present with a platelet count of less than 50,000 and may present with bleeding, however they may be asymptomatic.  

Treatment of ITP is often indicated when the platelet count decreases to less than 30,000 microL or if significant bleeding occurs.[4] Treatment options can include a regimen of corticosteroids (effective 50–80% of the time), splenectomy for those who don’t respond to corticosteroids, and for those cases where surgery is not indicated, treatment with rituximab, a monoclonal antibody with a 25–50% response rate. Other third-line approaches include Rh₀(D) immune globulin, azathioprine, ophosphamide, danazol, vinca alkaloids, dapsone, cyclosporine, and mycophenolate mofetil. All have modest response rates, and, in the case of immunosuppressive agents, an increased risk of infection, which can complicate treatment.  

Many current treatments attack the problem of ITP by attempting to interfere with platelet destruction. Increasingly, thrombopoietic agents are being studied as a potential treatment course for ITP. An approach currently studied in clinical trials is AMG 531.  This novel approach stimulates platelet production. Bussel et al. conducted a clinical trial published in the New England Journal of Medicine evaluating AMG 531 in the treatment of ITP among patients who had received prior treatment.³ AMG 531 demonstrated platelet responses in 68% of these patients with no major adverse events reported.

Conclusion  

Thrombocytopenia remains a common side effect among patients with cancer undergoing chemotherapy. However, several different types of thrombocytopenia also affect the lives of a significant portion of patients in the United States. 

There appear to be multiple mechanisms involved in thrombocytopenia. Though the exact mechanism in which the ITP or thrombocytopenia process is initiated is unclear, it seems only prudent to pursue emerging avenues of treatment, such as thrombopoietic agents. Follow-up results and future clinical trials involving thrombopoietic agents will provide further data on the clinical effectiveness and safety of these agents, and may provide a novel therapeutic approach to the treatment of thrombocytopenia. 

To successfully complete this CME activity, please read the additional articles from the 2007 ONS Conference Coverage before you take the post test:

Strategies for Preventing Infection in Cancer Patients with Neutropenia 
Lillian Nail, PhD, RN, FAAN, Rawlinson Professor & Senior Scientist, Oregon Health & Science University School of Nursing, Portland, Oregon

Myelosuppression: Oncology Nursing Society Congress 2007 
Lillian Nail, PhD, RN, FAAN, Rawlinson Professor & Senior Scientist, Oregon Health & Science University School of Nursing, Portland, Oregon

2007 ONS Congress: Issues and Prospects in Colorectal Cancer 
Lillian Nail, PhD, RN, FAAN, Rawlinson Professor & Senior Scientist, Oregon Health & Science University School of Nursing, Portland, Oregon 

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