Care of the Cancer Patient with Neutropenia or Thrombocytopenia

Chapter 24


Care of the Cancer Patient with Neutropenia or Thrombocytopenia



Cancer patients may become critically ill as a result of disease- or therapy-related complications. This is particularly true of patients with hematologic malignancies or those undergoing hematopoietic cell (i.e., bone marrow) transplantation (HCT). One common problem among oncology patients is the development of cytopenias, which, among other issues, can result in life-threatening infection or bleeding. This chapter focuses on the management of neutropenia and thrombocytopenia in the cancer patient requiring admission to the intensive care unit (ICU).



Clinical Disorders



Neutropenia


The absolute neutrophil count (ANC) is defined as follows:


image (Equation 24.1)


Mild neutropenia is defined as an ANC of 1000 to 1500 cells/μL, although patients are not commonly referred to as neutropenic until their ANC declines to < 1000 cells/μL. Moderate neutropenia is defined as an ANC of 500 to 1000 cells/μL, and severe neutropenia as an ANC < 500 cells/μL. In cancer patients, neutropenia can develop as a manifestation of cancer itself (particularly in patients with hematologic malignancies) or as an expected consequence of cytotoxic chemotherapy. In either case, neutropenic patients are prone to developing infections (which can also be a cause of or further exacerbate neutropenia) and frequently demonstrate inadequate activation of their immune and inflammatory systems when challenged with an infection. Accordingly, the development of fever in a neutropenic patient is considered a medical emergency that requires immediate action (refer to “Febrile Neutropenia” later in this chapter).


Identifying the etiology of neutropenia can be useful in predicting its expected duration and depth. The duration of chemotherapy-induced neutropenia varies based on the particular drug regimen but is almost always brief and largely predictable. In general, the white blood cell (WBC) count will begin to decline within 5 to 7 days from the initiation of chemotherapy, which is followed by a period of moderate to severe neutropenia of 3 to 10 days in duration. The lowest point (i.e., lowest WBC count) is referred to as the nadir. In most instances, the bone marrow is expected to recover fully and neutropenia will resolve accordingly. However, timing of the nadir and recovery may vary in patients with underlying bone marrow dysfunction resulting from the malignancy itself, effects of repeated cycles of cytotoxic chemotherapy, or marrow suppression sometimes associated with infection, and also depends on the chemotherapeutic agents administered.


Neutropenia can also occur prior to the initiation of chemotherapy in patients with hematologic malignancies, particularly acute myelogenous leukemia (AML) and the closely related myelodysplastic syndromes (MDS), as well as acute lymphoblastic leukemia (ALL). Neutropenia is infrequently seen in patients with chronic lymphocytic leukemia (CLL) and may be attributed to bone marrow replacement with CLL or, in rare cases, to autoimmunity. Additionally, the nonmalignant condition of severe aplastic anemia is manifested by neutropenia as well as other cytopenias. The degree and duration of neutropenia associated with these diseases can vary greatly, and the actual duration may be unknown in a patient who is newly diagnosed. Unfortunately, patients with hematologic malignancies frequently remain neutropenic until their underlying disease responds to therapy, which can take weeks or even months in some cases.


Finally, neutropenia almost always develops during allogeneic (donor) and autologous (self) hematopoietic cell transplantation as a result of conditioning with high doses of chemotherapy, radiation therapy, or both. Cancer patients receiving these therapies typically remain neutropenic until the time of engraftment (i.e., the production of new blood cells). This period of neutropenia typically lasts for 2 to 3 weeks, although it is not uncommon for the duration to be shorter in patients receiving reduced-intensity or nonmyeloablative conditioning regimens for allogeneic transplants. Nevertheless, these patients are highly immunocompromised because of the presence of a donor-derived immune system as well as the need for immunosuppressive medical therapy such as calcineurin inhibitors. The details of hematopoietic cell transplantation are beyond the scope of this chapter. However, the ICU provider should always seek consultation from the hematology-oncology service when managing patients undergoing this treatment modality because of the profound immunosuppression and other unique features associated with this form of therapy.


Box 24.1 gives the differential diagnosis for neutropenia in the ICU cancer patient.



BOX 24.1   Differential Diagnosis of Neutropenia in the ICU Cancer Patient





Thrombocytopenia


Thrombocytopenia is defined as a platelet count of < 150,000 cells/μL, although clinically significant bleeding rarely occurs at a platelet count of > 50,000 cells/μL unless disseminated intravascular coagulation (DIC) coexists. The risk of spontaneous bleeding is highest when the platelet count is < 10,000 cells/μL. The etiology of thrombocytopenia in cancer patients is often related to the disease or its therapy (Box 24.2), but causes may also be similar to those seen in the general population (which are addressed in more detail in Chapters 45 and 63).



BOX 24.2   Differential Diagnosis of Thrombocytopenia in the ICU Cancer Patient




∗See Chapters 45 and 63 for more details regarding these diagnoses.


As with neutropenia, thrombocytopenia in cancer patients can be associated with chemotherapeutic agents in both standard and high doses as well as hematologic malignancy. Infection with or without evidence of sepsis is common in oncology patients and can be associated with thrombocytopenia as well. Isolated thrombocytopenia in the oncology patient may be the result of etiologies seen in the general population such as (nonchemotherapy) drug-induced thrombocytopenia including heparin-induced thrombocytopenia (HIT) as well as DIC, thrombotic thrombocytopenic purpura (TTP), or idiopathic thrombocytopenic purpura (ITP) (see Chapters 45 and 63).


In particular, thrombocytopenia associated with a coagulopathy (whether apparent clinically or by laboratory testing) with or without microangiopathic hemolytic anemia (MAHA) should raise suspicion for DIC, which is manifested by consumption of elements in the coagulation cascade resulting in hemorrhage or thromboses. Acute DIC is a well-recognized complication of acute promyelocytic leukemia (APL) as well as sepsis, whereas chronic DIC is more commonly associated with solid tumor malignancies.


Finally, another cause of thrombocytopenia associated with MAHA but not usually a prolonged PT/PTT is thrombotic thrombocytopenic purpura (TTP), an abnormality of hemostasis characterized by the formation of platelet thrombi often leading to end-organ damage. Analogous to this diagnosis is that of transplantation-associated thrombotic microangiopathy, which is a phenomenon seen in the setting of allogeneic hematopoietic cell transplantation and may be attributed to conditioning chemotherapy or radiation therapy or to the calcineurin inhibitors used for posttransplantation immunosuppression.


Box 24.2 gives the differential diagnosis for thrombocytopenia in the ICU cancer patient.



Diagnostic Evaluation


A thorough history and physical examination are the first steps in properly evaluating a cancer patient with neutropenia or thrombocytopenia admitted to the ICU. If possible, patients or families should be questioned regarding any recent or current signs or symptoms of infections of the upper and lower respiratory system, gastrointestinal system including the rectum, urinary tract, and skin (particularly in those with indwelling vascular or urinary catheters). Patients with thrombocytopenia should be asked about signs or symptoms indicative of major bleeding events such as intracranial, pulmonary, and gastrointestinal hemorrhage as well as more minor events including epistaxis, gingival bleeding, hematuria, or the development of ecchymoses or petechiae.


Certain physical exam maneuvers are crucial to the evaluation of neutropenic and thrombocytopenic cancer patients. The skin should be carefully inspected for any areas of infection, particularly at or around sites of indwelling catheters (discussed later), as well as for petechiae and ecchymoses. Visualization of the oropharynx can reveal thrush, dental infections, gingival bleeding or mucositis, which is common in patients receiving chemotherapy. The abdomen should be examined for evidence of tenderness, which could indicate abscess or hemoperitoneum, as well as splenomegaly, which may contribute to thrombocytopenia. A digital rectal exam should not be performed on neutropenic patients because there is a high risk of provoking bacterial translocation into the bloodstream with manipulation of the rectum, but a visual examination is appropriate. It is important to note that neutropenic patients often lack the ability to produce a normal inflammatory response and may not demonstrate typical signs of infection.


Relevant laboratory testing in these patients includes a complete blood count (CBC) with differential along with a review of a peripheral blood smear. These tests will confirm neutropenia (which can occur even when a leukocytosis is present) and allow for evaluation for immature white blood cell forms or blasts indicative of acute leukemia and for the presence of toxic granulations or Döhle bodies in peripheral neutrophils (indicating severe acute inflammation). Additional blood testing should include serum chemistry panel, liver function tests, uric acid level, and lactic dehydrogenase (LDH) to evaluate for metabolic abnormalities resulting from rapid cell destruction termed tumor lysis syndrome, and finally prothrombin/partial thromboplastin times (PT/PTT), fibrinogen, fibrin split products, and D-dimer to assess for the presence of DIC. Additionally, cultures of the blood (two sets with at least one drawn directly from peripheral blood [Chapter 14]) and urine should be collected in febrile patients (particularly at the onset of a neutropenic fever as discussed later). Radiographic evaluation should be tailored appropriately based on the history and physical exam but almost always includes a chest radiograph. Computerized tomography (CT) scans can be useful in identifying complications of thrombocytopenia and neutropenia such as intracranial hemorrhage, fungal sinusitis, pneumonia, or neutropenic enterocolitis (also termed typhlitis) (Chapter 60). Additional diagnostic testing unique to these patients may include a bone marrow aspiration and biopsy, which the hematology-oncology consulting service should perform.

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Jul 7, 2016 | Posted by in CRITICAL CARE | Comments Off on Care of the Cancer Patient with Neutropenia or Thrombocytopenia

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