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42 Part I: Clinical Evaluation of the Patient Chapter 4: Consultative Hematology 43

symptoms of photosensitivity, arthralgia, and recurrent pregnancy mor- surrounding the development of anemia may also provide clues, as well
bidity should trigger rheumatologic consultation. as indicate if additional abnormalities in the other cell lines are present.
Hematolymphoid neoplasias may present with either acute or The physical should be a comprehensive exam with particular
chronic cytopenias. When considering the presence of malignancy, attention to lymphadenopathy, liver/spleen size, and assessment of
one should attempt to identify other concerning findings, such as other cardiovascular status. Laboratory analysis requires a current complete
cytopenias, adenopathy, fever, organomegaly, or unintentional weight blood count (CBC) and a blood film. Critically, one cannot rely on
loss, in addition to isolated neutropenia. an isolated hemoglobin value without the remainder of the CBC. An
absolute reticulocyte count, corrected for the degree of anemia, is also
LYMPHOPENIA required. A comprehensive metabolic panel as well, including renal and
liver function tests, is useful in narrowing the differential.
Lymphopenia, defined as an absolute lymphocyte count (ALC) less than If the anemia is of recent origin with a normal MCV and a low
1500 cells/μL, may be seen in a variety of settings. One should begin by corrected absolute reticulocyte count (meaning there is a production
assessing the chronicity and severity of lymphopenia, along with a thor- defect), then anemia of chronic disease (ACD) (Chap. 37) is likely.
ough physical examination. The latter should focus on any evidence of Additional labs evaluating inflammatory activity, such as ferritin, ery-
splenomegaly, adenopathy, or evidence of fungal infection, such as oral throcyte sedimentation rate (ESR), and C-reactive protein (CRP),
candidiasis. The numerous inherited and acquired causes of lymphope- may be helpful. If there is a RBC production defect, but no evidence
nia are noted in Chap. 79. of inflammatory disease, it is important to exclude renal dysfunc-
Notably HIV infection should be excluded in the lymphopenic tion. In this setting, we evaluate serum creatinine and erythropoietin
patient. Similarly, a concomitant infection with a number of viral or levels.
bacterial pathogens may result in lymphopenia. One of the most com- One must maintain a high suspicion for iron deficiency, even in
mon iatrogenic causes of lymphopenia is the use of glucocorticoids. the setting of a normal MCV and blood film (Chap. 43). Useful items
Alcoholism may also result in lymphopenia. include a ferritin, transferrin saturation, and clinical evaluation for
blood loss. Conversely, consider a patient in which the hemoglobin is
10.5 g/dL, MCV 64 fL, MCH 19 pg, and absolute reticulocyte count is
MONOCYTOPENIA elevated to 180,000. The blood film shows microcytic, hypochromic
Although monocytopenia is described in a number of settings RBCs with occasional target cells. Although iron levels should be deter-
(Chap. 70), the most notable entity to exclude is hairy cell leukemia. mined, thalassemia will be much more likely (Chap. 48).
Although rare, this B-cell lymphoproliferative disorder presents with If the MCV is greater than 100 fL and the reticulocyte count suggests
constitutional symptoms, splenomegaly, and the majority of patients a production defect, examine both the WBC and platelet number and
are monocytopenic as well as neutropenic (Chap. 93). Thus, in a patient morphology. If either is abnormal, then primary marrow disorders such
with compatible symptoms and monocytopenia, even without classic as MDS become more likely than nutritional deficiencies such as vitamin
hairy cells on the blood film, it is worthwhile performing flow cytom- B or folate. A marrow biopsy should be performed in this setting.
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etry with attention to hairy cell markers, including clonal designator If the rate of hemoglobin fall is greater than 1 percent/day, and
(CD) 11c and CD103. the corrected reticulocyte count is elevated, bleeding or hemolysis is
Severe monocytopenia may rarely be seen in the MonoMAC occurring. One should search for specific RBC morphologic anoma-
(monocytopenia and mycobacterial infection) syndrome. Described in lies on the blood film. If spherocytes, fragmented cells, or Heinz bodies
2010, it is associated with extreme monocytopenia or amonocytosis, may (Chaps. 2 and 31) are present, then hemolysis is likely. We obtain a hap-
be associated with mycobacterial and viral infections and results from a toglobin, indirect bilirubin, lactate dehydrogenase (LDH), and a direct
mutation in the GATA-2 gene. It has a high risk of progressing to MDS or Coombs study. The history is informative. If the hemolysis is lifelong,
acute myelogenous leukemia (Chap. 70). then RBC intracorpuscular defects (either of hemoglobin, membrane,
or enzymes [Chaps. 46, 47, and 49]) are likely. If the hemolysis is recent,
then acquired extracorpuscular causes, such as autoimmune hemoly-
ANEMIA sis, parasitic disease, renal/hepatic disease, or hypersplenism, are likely
(Chaps. 51 to 54 and 56).
The underlying pathophysiology of the anemia must be identified. We If the anemia is persistent, symptomatic, and the aforementioned
use three interacting analytic tools: workup has not provided a diagnosis, then marrow biopsy and aspira-
tion are indicated.
1. Standard hematologic indices, particularly mean corpuscular vol-
ume (MCV) and mean corpuscular hemoglobin (MCH).
2. Kinetic analysis (Chaps. 32 and 33) seeking to determine if the THROMBOCYTOPENIA
underlying cause is a defect in red blood cell (RBC) production, an
increase in RBC destruction (hemolysis), or blood loss. Humans Whereas the consultative approach to thrombocytosis is relatively
replace 1 percent of their RBCs per day (Chap. 32). Any decrease in straightforward, the opposite is true for thrombocytopenia. The clini-
hemoglobin greater than 1 percent/day implies the patient is bleed- cal situation may be urgent and the differential diagnosis, upon which
ing, hemolyzing, or both. management is based, is huge (Chap. 117). It is helpful to think of the
3. An awareness of patient demographics. For example, a pediat- underlying cause(s) mechanistically:
ric practice may place hemoglobinopathies high on the differen-
tial, whereas a geriatric internal medicine practice will commonly • Platelet production is low: The marrow is replaced (leukemia, lym-
encounter anemia of chronic disease and iron deficiency. phoma), empty (aplastic anemia), or ineffective (MDS, vitamin B
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deficiency).
The history and medical records are important tools in identifying the • Platelets are being rapidly removed from circulation: Thrombotic
severity and duration of anemia. The timeline of development is crucial: microangiopathy (thrombotic thrombocytopenic purpura [TTP],
if it has been lifelong, congenital causes are likely. If not, then the events hemolytic uremic syndrome [HUS], disseminated intravascular

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