Page 65 - Williams Hematology ( PDFDrive )

41

CHAPTER 4 In this chapter, we outline our approach to dealing with these common

CONSULTATIVE queries. The individual epidemiology, pathogenesis, and treatment of such
disorders are covered comprehensively and with clarity within their corre-
HEMATOLOGY sponding chapters and are not repeated here. Rather, what we describe is our
thought process in approaching such questions and narrowing the broad dif-
ferential to that which is reasonable and probable.

Rondeep S. Brar and Stanley L. Schrier

SUMMARY LEUKOPENIA

Hematology is a unique science in that its complexity is readily accessible via Detection of a low white blood cell (WBC) count is a common reason
the examination of blood and marrow. The ease with which a complete blood for hematologic consultation. Clinicians and patients are attentive to
count (CBC) may be obtained also leads to frequent observation of values early signs of marrow pathology, such as myelodysplastic syndrome
which fall outside the reference range. Such perturbations may be the sign of (MDS), although such diseases are found only in a minority of referrals.
something as ominous as acute leukemia, or as inconsequential as the com- Nevertheless, the severity of potential pathology mandates leukopenia
mon cold. That such changes might generate considerable anxiety, both for be taken seriously and approached thoughtfully.
patients and providers, is not surprising given the plethora of life-threatening One begins by determining if the predominant finding is neutro-
diseases that often manifest classic CBC findings. penia, lymphopenia, monocytopenia, or all of the above.
This ever-increasing dependence on labs as screening tools generates a
seemingly endless supply of “abnormal” results, often triggering hemato- NEUTROPENIA
logic consultation. Electronic medical records (EMRs), as repositories for this The potential causes of neutropenia are diverse and include congenital
ever-growing data, serve as invaluable tools in evaluating the chronicity and disorders, autoimmune disorders, infections, nutritional deficiencies,
trend of such findings. medications, and, of course, hematolymphoid neoplasias. These are dis-
cussed in detail in Chap. 65.
Degrees of neutropenia may be broadly classified as mild (abso-
lute neutrophil count [ANC] 1000–1500 cells/μL), moderate (ANC
500–1000 cells/μL), or severe (ANC <500 cells/μL).
The three most important historical details are the degree of neu-
Acronyms and Abbreviations: AC, anticoagulation; ACD, anemia of chronic dis- tropenia, acuity of onset, and presence or absence of associated symp-
ease; ADAMTS13, a disintegrin and metalloprotease with a thrombospondin type 1 toms. Each is considered individually and within the context of other
motif member 13; ALC, absolute lymphocyte count; ALL, acute lymphoblastic leu- findings.
kemia; ANC, absolute neutrophil count; APS, antiphospholipid antibody syndrome; The degree of neutropenia is informative. There is no specific
BCR-Abl, breakpoint cluster region-Abelson; CBC, complete blood count; CD, clonal ANC threshold that mandates evaluation. In general, mild neutropenia
designator; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leuke- with preservation of other lineages in the asymptomatic patient may
mia; CMML, chronic myelomonocytic leukemia; CNL, chronic neutrophilic leukemia; be observed, whereas moderate or severe neutropenia increases the
CRP, C-reactive protein; DIC, disseminated intravascular coagulation; DVT, deep risk of infection and probability of underlying pathology. The degree of
venous thrombosis; EDTA, ethylenediaminetetraacetic acid; EMR, electronic medical neutropenia is not a priori a measure of its potential consequences. For
record; EPO, erythropoietin; ER, emergency room; ESR, erythrocyte sedimentation example, patients with chronic idiopathic neutropenia may have blood
rate; ET, essential thrombocythemia; HELLP, hemolysis, elevated liver enzymes, neutrophil counts approaching zero with no symptoms or increased
low platelet count; HHT, hereditary hemorrhagic telangiectasia; HIT, heparin- risk of infection.
induced thrombocytopenia; HUS, hemolytic uremic syndrome; ITP, immune throm- The acuity of neutropenia is quite helpful, and the advent of the
bocytopenia; JAK2, Janus kinase 2; LDH, lactate dehydrogenase; LGL, large granular electronic medical record (EMR) allows for the rapid evaluation of such
lymphocytic; LMWH, low-molecular-weight heparin; MCH, mean corpuscular hemo- trends. In acute onset neutropenia, it is useful to inquire about recent
globin; MCV, mean corpuscular volume; MDS, myelodysplastic syndrome; MGUS, infections and new medications. The latter is often an important clue.
monoclonal gammopathy of undetermined significance; MPN, myeloprolifera- The number of medications that might cause neutropenia is vast, and
tive neoplasm; MTHFR, methylenetetrahydrofolate reductase; nRBC, nucleated some representative agents are shown in Chap. 65, Table 65–1. The
red blood cell; NSAID, nonsteroidal antiinflammatory drug; p50, partial pressure temporal association of new medications with cytopenias is often the
required to achieve 50 percent saturation; PCR, polymerase chain reaction; PE, strongest evidence of causality. If there is suspicion for drug-induced
pulmonary embolism; PFA, platelet function analysis; PMN, polymorphonuclear neutropenia, the offending medication should be discontinued. If this is
neutrophil; PNH, paroxysmal nocturnal hemoglobinuria; PT, prothrombin time; not possible, switching to a congener with a different chemical structure
PTT, partial thromboplastin time; PV, polycythemia vera; RBC, red blood cell; RIPA, should be strongly considered.
ristocetin-induced platelet aggregation; RT, reptilase time; SPEP, serum protein In cases of chronic neutropenia, one should explore possibilities
electrophoresis; TT, thrombin time; TTP, thrombotic thrombocytopenic purpura; such as congenital neutropenia, chronic idiopathic neutropenia, infec-
UPEP, urine protein electrophoresis; VWD, von Willebrand disease; WBC, white tion particularly hepatitis and HIV, and autoimmune disorders. With
blood cell. respect to the latter, systemic lupus erythematosus is important to be
cognizant of, as nearly half of such patients will be leukopenic. Thus

Kaushansky_chapter 04_p0041-0050.indd 41 17/09/15 5:39 pm