Download 203 - White Blood Cell Disorders

203 White Blood Cell Disorders
Eric Goralnick
KEY POINTS
• White blood cell disorders are the result of cell
overproduction, underproduction, or dysfunction.
• Hematologic malignant diseases have variable initial
presentations and significant associated complications.
• Rapid evaluation and intervention are essential to
minimize morbidity and mortality in the
immunocompromised patient.
EPIDEMIOLOGY
The National Cancer Institute estimated that approximately
137,260 new cases and 54,020 deaths from hematologic
malignant diseases (leukemias, lymphomas, and plasma cell
disorders) occurred in 2010. On January 1, 2007, approximately 908,512 men and women living in the United States
had a history of hematologic malignant disease. In adults,
non-Hodgkin lymphomas and chronic lymphocytic leukemia
are the most common of these diseases.1 Of a total of 26,446
childhood cancers (age 1 to 19 years) diagnosed in the United
States from 2001 to 2003, leukemias were the most common
(26.3%). The lymphoid leukemias were the type with the
highest incidence. Lymphomas, comprising 14.6% of new
childhood malignant diseases, were the third most common
cancers.1,2 A history of malignant disease is a common feature
in the emergency department (ED) patient population. In a
retrospective review of 5640 patients in a community teaching
hospital with an annual ED census of 31,000, cancer history
was identified in 5% of patients. Ten percent of patients with
oncology-related visits died during the admission, and 48%
died within 1 year of the ED visit.3
PATHOPHYSIOLOGY
White blood cells (WBCs), or leukocytes, are the primary
cells responsible for the inflammatory and immune response.
WBCs include granulocytes (neutrophils, eosinophils, basophils) and mononuclear cells (T and B lymphocytes,
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monocytes). These cells are all produced from a common
stem cell in the bone marrow, and they differentiate through
various cytokines including colony-stimulating factors and
interleukins. Normal blood leukocyte counts are 4.34 to 10.8
× 109/L, with neutrophils representing 45% to 74% of cells,
bands representing 0% to 4%, lymphocytes representing 16%
to 45%, monocytes representing 4% to 10%, eosinophils representing 0% to 7%, and basophils representing 0% to 2%.4
WBC disorders are the result of cell overproduction, underproduction, or dysfunction (Box 203.1). The WBC count with
differential lacks specificity and sensitivity but is the most
frequent laboratory test ordered by emergency physicians.5
LEUKOPENIA
Leukopenia, or a WBC count less than 1.5 × 109/L, is most
clinically relevant with significant neutropenia and its complications (primarily increased risk of infection, further outlined in Chapter 201). Although neutropenia is most common
in patients with bone marrow suppression secondary to chemotherapy, Box 203.2 outlines a differential diagnosis of
certain infections that characteristically manifest with neutropenia. Lymphocytopenia is a nonspecific finding that is present
in many bacterial, fungal, viral, and protozoan infections.6
LEUKOCYTOSIS
Leukocytosis, or an increased number of WBCs, is defined as
an elevation in the total number of circulating WBCs greater
than 2 standard deviations above the age-based mean circulating WBC count. This disorder is most commonly secondary
to infections or systemic stressors; however, an increase in a
subset of WBCs (neutrophilia, monocytosis, lymphocytosis,
eosinophilia, or basophilia) may guide the differential diagnosis. Bacteria are the culprit in two thirds of infection-related
cases of neutrophilia.7 Box 203.3 outlines infectious causes of
lymphocytosis, with Bordetella pertussis being the rare bacterial exception. Eosinophilia is classically caused by multicellular parasites that invade tissue, most commonly seen in
invasive parasitic disease, but it may also be seen in protozoan
and fungal infections.8
MORPHOLOGIC CHANGES
In addition to altered numbers, changes in cellular morphology found in a peripheral blood smear may aid in the
diagnosis. A left shift (or greater percentage of immature
cells, such as metamyelocytes) may be present in severe infection. Intracellular abnormalities including toxic granulations,
CHAPTER 203
White Blood Cell Disorders
BOX 203.1 Differential Diagnosis of White
Blood Cell Disorders by Pathogenesis
BOX 203.2 Infections That May Cause
Neutropenia in the Normal Host
Overproduction
Bacterial
• Salmonellosis
• Tularemia
• Brucellosis
• Rickettsial disease (Rocky Mountain spotted fever)
• Miliary tuberculosis
Stress (Infections, Inflammation)
Drugs
• Corticosteroids
• Granulocyte colony-stimulating factor
• Acetylcholine
• Adrenergic agents
• Heparin
• Lithium
• Histamine
• Lead
• Iron
Neoplastic Disease
Primary Hematologic
• Myelodysplastic syndromes
• Acute leukemias
– Acute myelogenous leukemia
– Acute lymphocytic leukemia
• Chronic leukemias
– Chronic lymphocytic leukemia
– Chronic myelogenous leukemia
– Hairy cell leukemia
– Large granular lymphocytic leukemia
• Non-Hodgkin lymphoma
Cancers Metastatic to Bone
• Most commonly breast, lung, prostate, and lymphomas
Viral
• Measles
• Varicella (chickenpox)
• Rubella
• Influenza
• Infectious hepatitis
• Yellow fever
• Sandfly fever
• Human immunodeficiency virus infection
• Colorado tick fever
• Dengue fever
Protozoan and Parasitic
• Malaria
• Kala-azar
• Relapsing fever
Adapted from Hoffman R, Benz Jr EJ, Shattil SJ, et al, editors. Hematology: basic principles and practice. 5th ed. Philadelphia: Churchill Livingstone; 2009.
Underproduction
Drug or Toxin Suppression
• Cancer chemotherapy
• Phenytoin
• Penicillins
• Sulfa
Aplastic Anemia
Malignant Disease (Leukemia, Myelodysplastic
Syndrome)
Vitamin B12 or Folate Deficiency
Dysfunction
Increased Splenic Sequestration
• Cirrhosis
• Gaucher disease
Diabetes Mellitus
• Impaired polymorphonuclear neutrophil function
Chronic Renal Failure
• Impaired polymorphonuclear neutrophil and lymphocyte
function
Drugs
• Corticosteroids
BOX 203.3 Infections That May Cause
Lymphocytosis
Acute Infection
• Pertussis
• Infectious mononucleosis
• Infectious hepatitis
• Acute infectious lymphocytosis
• Toxoplasmosis
• Cytomegalovirus
Chronic Infection
• Tuberculosis
• Brucellosis
• Syphilis
• Rickettsial disease
Adapted from Hoffman R, Benz Jr EJ, Shattil SJ, et al, editors. Hematology: basic principles and practice. 5th ed. Philadelphia: Churchill Livingstone; 2009.
Adapted from Lepin HD, Powell BL. White cell disorders. In: Halter JB,
Ouslander J, Tinetti M, et al, editors. Hazzard’s geriatric medicine and
gerontology. 6th ed. New York: McGraw-Hill; 2009.
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Fig. 203.1 Reactive changes in neutrophils. Neutrophils
containing coarse purple cytoplasmic granules (toxic granulations)
and blue cytoplasmic patches of dilated endoplasmic reticulum
(Dohle bodies; arrow) are observed in this peripheral blood smear
prepared from a patient with bacterial sepsis. (From Kumar V,
Abbas, AK, Fausto N, Aster J, editors. Robbins and Cotran
pathologic basis of disease. 8th ed. Philadelphia: Saunders; 2009.)
cytoplasmic vacuolization, and Dohle bodies are likely secondary to infection (Fig. 203.1).6
WHITE BLOOD CELL MALIGNANCY
Although WBC disorders have a vast differential diagnosis,
the remainder of this chapter focuses on hematologic malignant diseases. Leukemias, lymphomas, and plasma cell disorders are the main general categories of these malignant
diseases.
Leukemias are a result of failure of differentiation of hematopoietic precursor cells that leads to unchecked proliferation
of blasts, either immature myeloid or lymphoid cells, which
impede the normal manufacturing of red blood cells, WBCs,
and platelets in the bone marrow. Anemia, bleeding, and
infection are a result of decreased normal cell production.
Eventually, blasts multiply and migrate throughout other
hematopoietic organs including the spleen and lymph nodes.
In acute leukemias, WBC counts vary greatly (25% of patients
have counts <5000/microliters, 25% have counts >50,000/
microliters, and 50% have counts between 5000 and 50,000/
microliters), but anemia, thrombocytopenia, and blasts are
common. Bone marrow aspiration and biopsy are used to
diagnose leukemias definitively.
Lymphomas are a vast group of malignant diseases defined
by clonal proliferation of malignant lymphocytes. The World
Health Organization lymphoma classification defined 27 types
of lymphomas categorized primarily by the primary clonal
cells: B cells, T cells, or natural killer cells. Lymphocytosis
and varied characteristic cells are present on a peripheral
blood smear. Lymph node and bone marrow biopsy also aid
in the diagnosis.
Monoclonal proliferation of immunoglobin-secreting
plasma cells characterizes plasma cell disorders. These conditions include multiple myeloma, monoclonal gammopathies,
Waldenström macroglobulinemia, heavy-chain diseases, cryoglobulinemia, and primary amyloidosis. These diseases are
diagnosed by using serum or protein electrophoresis and bone
marrow analysis.
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Fig. 203.2 Leukemia cutis in a patient with monoblastic
leukemia. (From Miller KB, Pihan G. Acute myeloid leukemia. In:
Hoffman R, Benz Jr EJ, Shattil SJ, et al, editors. Hematology: basic
principles and practice. 5th ed. Philadelphia: Churchill Livingstone;
2009.)
PRESENTING SIGNS AND SYMPTOMS
Nonspecific presentations of liquid malignant diseases are
common, but prompt recognition of these signs and symptoms
is essential for rapid treatment of immunocompromised
patients. Initial presentations of malignancy vary greatly from
subtle historical features or physical findings to in extremis
shock states typically resulting from complications and grave
immunodeficiency. Patients with known malignant disease
also have variable presenting complaints based on the type of
malignant disease, the burden of disease, and current oncologic therapeutic regimens.
ACUTE MYELOGENOUS AND LYMPHOID
LEUKEMIAS
Acute Myelogenous Leukemia
Patients with leukemia present with signs and symptoms secondary to the invasion of other organs by leukemic cells and
decreased production of normal hematopoietic cells. Fever,
malaise, and a viral-like syndrome are common presenting
symptoms. Diffuse bony tenderness, as a result of expansion
of the intramedullary space or periosteal infiltration by leukemic cells, is the initial symptom in 25% of patients.9
Acute myelogenous leukemia (AML) typically affects all
three cells lines and results in anemia, thrombocytopenia, and
neutropenia. Pallor, dyspnea, and chest pain reflect anemia,
whereas petechiae, ecchymosis, and excessive bleeding are a
result of thrombocytopenia. One third of patients will have
significant infections on diagnosis.10 Splenomegaly occurs in
up to 50% of patients, and lymphadenopathy is rare.9
AML has several skin manifestations. Raised, nontender
plaques or nodules (leukemia cutis) are manifest in many
forms of leukemia, but they are most commonly seen in AML
(Fig. 203.2).11 Tender, pseudovesicular, erythematous plaques
are a characteristic feature of Sweet syndrome, which may
precede the diagnosis of AML by months (Fig. 203.3). Gingival hyperplasia may also be present (Fig. 203.4).
CHAPTER 203
White Blood Cell Disorders
Rights were not granted to include this figure
in electronic media.
Please refer to the printed publication.
Fig. 203.3 Sweet syndrome in a patient with acute myeloid
leukemia. Tender, pseudovesicular, erythematous plaques are a
characteristic feature of this syndrome. (From Cohen PR. Acral
erythema: a clinical review. Cutis 1993;51:175, with permission.)
Fig. 203.5 Lytic lesions. (From Kyle RA, Rajkumar SV. Plasma
cell disorders. In: Goldman L, Ausiello DA, editors. Cecil textbook
of medicine. 22nd ed. Philadelphia: Saunders; 2004. pp.
1184–1195.)
CHRONIC MYELOGENOUS LEUKEMIA
Thirty percent to 50% of patients diagnosed with chronic
myelogenous leukemia are asymptomatic. Splenomegaly is
present in 50% to 60%, and hepatomegaly occurs in 10% to
20% of new cases. Lymphadenopathy is rare.13
NON-HODGKIN LYMPHOMA
Presentation of non-Hodgkin lymphoma is extremely variable, but patients most commonly seek medical evaluation for
incidental painless, firm cervical, axillary, or inguinal adenopathy. Chest pain, cough, superior vena cava syndrome, abdominal pain, back pain, spinal cord compression, and symptoms
of renal insufficiency may be present. Fevers, night sweats,
and weight loss are also common symptoms.
Fig. 203.4 Generalized gingival hyperplasia in a patient with
leukemia. (Courtesy of Dr. Edward V. Zegarelli. In: Ibsen OAC,
Phelan JA, editors. Oral pathology for the dental hygienist. 4th ed.
St. Louis: Mosby; 2004.)
Central or peripheral nervous system signs and symptoms
on initial presentation are rare, although cranial nerve palsies
(most commonly fifth and seventh) or meningeal signs have
been documented.10
CHRONIC LYMPHOCYTIC LEUKEMIA
Chronic lymphocytic leukemia has a wide spectrum of presentations, but most commonly patients are diagnosed after
an incidental finding such as enlarged lymph nodes (present
in two thirds of patients at diagnosis), a palpable spleen (found
in 40% of presenting patients), hepatomegaly (present in 10%
of patients with a new diagnosis), or abnormal blood test
results. Fatigue, lethargy, decreased appetite, weight loss, and
decreased exercise tolerance are nonspecific, but they are
again indicative of the effects of compromised hematopoiesis
of all three cell lines. Central nervous system infiltration is
rare; symptoms are more likely secondary to opportunistic
infections.12
HODGKIN LYMPHOMA
Fever, night sweats, and weight loss are the classic “B” symptoms associated with Hodgkin lymphoma. Other classic signs
are systemic pruritus and painful lymphadenopathy after
drinking alcohol. Painless, rubbery, supradiaphragmatic
lymphadenopathy, particularly of the neck and supraclavicular
nodes, is common. Less than 10% of patients will have a
subdiaphragmatic presentation.14
PLASMA CELL DISORDERS
Fatigue and bone pain are the most common presenting symptoms of multiple myeloma.15 Pain may be secondary to characteristic lytic lesions or pathologic fractures (Fig. 203.5).
Focal weakness or paresthesias may be secondary to nerve
root or spinal cord compression from extramedullary expansion of bony lesions.
DIFFERENTIAL DIAGNOSIS, MEDICAL DECISION
MAKING, AND TREATMENT
Once the diagnosis of a hematologic malignant disease is
suspected, laboratory evaluation should be performed, including a complete blood cell count with manual differential,
peripheral blood smear, chemistry studies (including uric acid,
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BOX 203.4 Differential Diagnosis of White Blood Cell Disorders by Signs and Symptoms
Fever (Nonlocalizing)
• Granulocytopenia
– Bacterial → fungal → breakthrough fungemia
– Since the late 1990s, great increase of gram-positive
organisms, often MRSA
• Cell-mediated immunodeficiency
– Viral
– Mycobacterial, fungal, nocardial, listerial
• Humoral immune deficiency
– B-cell, splenectomy related
Abdominal Pain
• Chemotherapy-related nausea and dehydration
• Splenomegaly
• Obstructive adenopathy: jaundice, uropathy, or small bowel
obstruction
• Organ-specific pain
– Ascites or spontaneous bacterial peritonitis
– Portal vein thrombosis
• Mesenteric ischemia
• Typhlitis (neutropenic enterocolitis)
• Zoster
• Constipation (opioid)
• Hypercalcemia
• Psychogenic (e.g., depression)
Dyspnea
• Pneumonia
• Pulmonary embolism
• Pleural effusion
• Pericardial effusion
• Pneumocystis pneumonia
•
•
•
•
•
Acute respiratory distress syndrome
Chemotherapeutic and radiographic toxicity
Hyperviscosity leukostasis
Paraneoplastic syndromes
Heart failure
– Chemotherapy related
• Adrenal insufficiency
• Thymus: pain and dyspnea with T-cell ALL infiltration
• Bronchiolitis obliterans organizing pneumonia
• Mass effect and obstruction
• Anemia
• Chronic obstructive pulmonary disease
• Anxiety disorder
• Superior vena cava syndrome
Malaise and Body Pains
• Elevated uric acid levels or gouty arthritis
• Osteolytic lesions
• Osteopenic fractures (corticosteroid induced)
• Hypercalcemia
• Oral mucositis
• Skin lesions
– Systemic (hairy cell) vasculitis
– Leukemia cutis
• Hyperviscosity leukostasis
• Tumor lysis syndrome
• Renal failure
• Anorexia of malignancy17
• Amyloidosis pains (accumulation of monoclonal plasma
cells in tissues and organs, frequently the heart)12
ALL, Acute lymphocytic leukemia; MRSA, methicillin-resistant Staphylococcus aureus.
creatinine, potassium, phosphorus, and calcium), coagulation
factors, and blood type and screen. If the patient is febrile,
blood cultures (aerobic, anaerobic, and fungal) should also be
obtained, and empiric antibiotics should be initiated early
because many of these patients have functional neutropenia,
even in the setting of normal neutrophil count, and are at high
risk of bacteremia or sepsis.16 Diagnostic imaging should be
ordered based on the focality of patients’ symptoms, but a
chest radiograph is a general starting point to evaluate any of
the intrathoracic complications associated with these malignant diseases. An electrocardiogram should be performed to
evaluate for evidence of electrolyte abnormalities.
Patients presenting with hyperleukocytosis (an extreme
elevation of the blast count or WBC count >100,000/mm3)
and many different symptoms affecting multiple organ
systems are at an increased risk of hyperviscosity syndrome
(see Box 203.5), a medical emergency with mortality rates as
high as 40%.17 Metabolic and electrolyte abnormalities are
common. The most serious complication is tumor lysis syndrome, a result of the massive cell lysis, which releases intracellular urate, phosphate, and potassium (please refer to
Chapter 201 for details on tumor lysis syndrome).
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CARDINAL PRESENTATIONS AND
COMPLICATIONS OF PATIENTS WITH
KNOWN WHITE BLOOD CELL CANCER
Abdominal pain, dyspnea, fever, and malaise are all key chief
complaints that require a comprehensive ED evaluation in
patients with WBC disorders. Box 203.4 lists the differential
diagnosis of these complaints.
ABDOMINAL PAIN
Gastrointestinal symptoms are the most common chief complaints of patients with cancer who present to the ED.3 Immunosuppressed patients represent a diagnostic challenge,
because classic examination findings of an acute abdomen
may be replaced by nonspecific signs or systems such as
tachycardia, hypotension, and altered mental status.18
In addition to disorders present in the immunocompetent
host, disorders secondary either to the malignant disease or to
the therapy used to combat it should be considered. Opportunistic infections, intestinal obstruction, perforation, typhlitis,
and venoocclusive disease of the liver (Budd-Chiari syndrome) should be considered in the differential diagnosis of
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A
White Blood Cell Disorders
B
Fig. 203.6 Typhlitis. A, Ultrasound scan showing thickened bowel wall. B, Axial computed tomography showing thickening of the wall
of the ascending colon. (From Adam A, Dixon AK, editors. Grainger and Allison’s diagnostic radiology. 5th ed. Philadelphia: Churchill
Livingstone; 2007.)
a patient with cancer who has an acute abdomen. In a retrospective series of patients with acute leukemia who developed
severe abdominal infections during chemotherapy-induced
neutropenia, 68% presented with enterocolitis (primarily bacteremia, but also fungal and viral infections).19 A broad diagnostic strategy, including abdominal diagnostic imaging
(computed tomography [CT] or ultrasound, or both), is usually
necessary in the thorough evaluation of these patients.
Typhlitis, or neutropenic enterocolitis, is a necrotizing
inflammation of the ascending colon or cecum that is a
common cause of the acute abdomen in a neutropenic patient
(Fig. 203.6).18 Although the incidence varies (from 0.8% to
26%), typhilitis has a mortality rate of 50% and higher.20 The
pathogenesis is unclear, but theories have implicated failed
mucosal integrity secondary to chemotherapy or the migration
of bacteria causing bowel necrosis and hemorrhage secondary
to the effects of neutropenia.21 Several case reports have
described typhlitis as a presentation of acute leukemia.22,23
Signs and symptoms vary. In a retrospective case review of
10 patients, all presented with fever, and some had abdominal
pain (most commonly right lower quadrant), nausea, diarrhea,
and hypotension.24 CT imaging shows bowel wall thickening
and cecal distention. Ultrasound imaging may show bowel
wall thickening but is not specific. Therefore, CT is recommended in addition to ultrasound, to assess potential complications, including colonic wall hemorrhage, pneumatosis
intestinalis, pneumoperitoneum, and abscesses, more thoroughly.25 Broad-spectrum antibiotics (covering enteric gramnegative organisms, Pseudomonas, and anaerobes including
Clostridium difficile), bowel rest, surgical evaluation, and supportive care are recommended.
Hepatic venous outflow obstruction caused by thromboses,
or Budd-Chiari syndrome, results from a hypercoagulable
state or direct tumor invasion of the hepatic venous system.
Venous stasis and hepatic congestion lead to cell death and
eventual liver failure.26 Symptoms include ascites, hepatomegaly, abdominal pain, jaundice, and, in severe cases, variceal bleeding and portal hypertension. Ultrasound scanning
with Doppler is the initial imaging modality of choice; it has
a sensitivity of more than 85%, but CT and magnetic resonance imaging are alternatives.27 The initial management
strategy consists of sodium restriction, diuretics, anticoagulation, and periodic paracentesis. Portosystemic shunting or
liver transplantation is indicated for severe forms of BuddChiari syndrome.26
DYSPNEA
Patients presenting to the ED with dyspnea should be
approached with a rapid assessment of respiratory status and
should be given immediate resuscitative care in the form of
supplemental oxygen, assisted ventilation, or intubation with
mechanical ventilation. Despite this initial universal approach
to the dyspneic patient, investigation of the broad differential
diagnosis is essential to formulating an emergency management plan.
Acute respiratory failure is the most common cause of
admission to the intensive care unit (ICU) in patients with
cancer, and it has an incidence of 10% to 50% and an overall
mortality rate of 50%.28 Patients with leukemia and lymphoma
have a higher incidence of respiratory insufficiency as the
cause of ICU admission than do patients with solid tumors.28
Common causes of acute respiratory failure in these patients
include pulmonary infections (pneumonia), cardiogenic or
noncardiogenic pulmonary edema, antineoplastic (chemotherapy or radiation) therapy-induced lung injury, venous
thromboembolism, diffuse alveolar hemorrhage (DAH),
airway obstruction, and underlying disease progression.29
Pneumonia is the most common cause of respiratory failure
in patients with hematologic malignant diseases. Streptococcus pneumoniae and Haemophilus influenzae are the most
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common organisms in patients with leukemia and myeloma
(impaired B-cell immunity). Patients with Hodgkin lymphoma
(impaired T-cell immunity) are more likely to be infected with
Pneumocystis jiroveci, mycobacteria and fungi, and viruses
(including cytomegalovirus and herpes simplex virus). Presentation may be atypical. Although fever is common, cough
and sputum are not, and findings on chest radiography may be
normal. Chemotherapy-induced neutropenia can give rise to
infection with Staphylococcus aureus, gram-negative bacilli
(Pseudomonas and Klebsiella), and opportunistic fungi
(Aspergillus).30 Debilitation, malnourishment, prolonged bed
rest, and central nervous system metastasis predispose oncologic patients to increased aspiration risk.31
Pulmonary edema may be cardiogenic, noncardiogenic, or
a combination thereof because of several inciting events,
including the use of cardiotoxic chemotherapeutic agents,
infection, radiation, or transfusions. These patients are at a
high risk of developing acute respiratory distress syndrome
(ARDS).
Chemotherapy- and radiation-induced lung injury comprises another syndrome that may manifest with exertional
dyspnea, low-grade fevers, and a nonproductive cough during
or up to several months after treatment. The various diagnoses
include interstitial pneumonitis, acute lung injury, ARDS, capillary leak syndrome, organizing pneumonia, hypersensitivity
reaction, bronchospasm, and DAH.30 On examination, bilateral
inspiratory crackles may be auscultated, and diffuse or patch
ground-glass opacities are seen on chest radiography and CT.
Each syndrome requires a multipronged approach, but cessation of the culprit chemotherapeutic agent and treatment with
systemic corticosteroids are general management principles.
Venous thromboembolism (deep venous thrombosis or pulmonary embolism) is an important cause of morbidity and
mortality in patients with cancer and may be a predictor of
worse overall prognosis.32 Chemotherapeutic agents, intrinsic
procoagulant tumor activity, indwelling catheters, immobilization, and surgery are risk factors for venous thromboembolism in oncologic patients. Ten percent of patients with
lymphoma develop venous thromboembolism.33 Presenting
symptoms of dyspnea, pleurisy, and palpitations and signs of
tachypnea, hypoxia, and dysrhythmias should prompt a thorough evaluation for venous thromboembolism.
DAH is common in patients with leukemia or multiple
myeloma, after bone marrow transplantation, and in patients
with thrombocytopenia (platelets < 50,000/mm3). Total body
irradiation, thoracic irradiation, and increased age are all risk
factors for DAH.30 Patients present with progressive dyspnea,
cough, and fever but rarely hemoptysis. Chest radiography
may show diffuse interstitial and alveolar infiltrates, and the
diagnosis is confirmed by bronchoscopy. Supportive therapy
includes corticosteroids, platelet transfusions, and mechanical
ventilator support.
Transfusion-related acute lung injury may develop in those
patients receiving red blood cells, platelets, or fresh frozen
plasma. Patients develop fever, hypotension, hypoxemia, pulmonary hypertension, and noncardiogenic pulmonary edema
within 6 hours of transfusion.34 Treatment is supportive and
often requires ventilatory support.
Airway obstruction may be secondary to locally advanced
tumors in the airway or metastatic lesions to the mediastinum
or tracheobronchial tree. Lymphoma may develop mediastinal
masses that may cause stridor, dyspnea, hemoptysis, or cough.
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Fig. 203.7 Chest radiograph showing pulmonary leukostasis
in a patient with monoblastic leukemia and a white blood cell
count of 150,000/mm3. (From Miller KB, Pihan G. Acute myeloid
leukemia. In: Hoffman R, Benz Jr EJ, Shattil SJ, et al, editors.
Hematology: basic principles and practice. 5th ed. Philadelphia:
Churchill Livingstone; 2009.)
Chest radiography, CT, and bronchoscopy are used in combination to establish a diagnosis and guide therapy. Definitive
airway management is difficult but may be essential in these
patients. Eventual treatment may consist of stents, lasers,
radiation therapy, or chemotherapy.
PAIN
The most common complaint of patients with cancer who
present to the ED is pain, with nausea or vomiting and weakness a close second and third most frequent chief complaints.3
Although pain is nonspecific, the ED physician needs to be
aware of critical, life-threatening diagnoses that may manifest
with pain.
Hypercalcemia may occur in up to 30% of patients with
cancer, and they may present with vague symptoms of nausea,
vomiting, abdominal pain, or myalgias.35 Hypercalcemia may
lead to progressive neurologic symptoms, coma, renal failure,
and arrhythmias. In multiple myeloma, hypercalcemia results
from bone osteoclastic bone resorption. Lymphomas and
myelomas hydroxylate vitamin D into 1,25-dihydroxyvitamin
D (1.25(OH)2D), the active form of vitamin D, thus enhancing intestinal absorption of vitamin D and resulting in hypercalcemia.35 This diagnosis is critical in this patient population
because approximately 50% of these patients will die within
30 days.36 The diagnosis is best made by using ionized
calcium, and an electrocardiogram may show a shortened QT
interval. The cornerstone of management is aggressive intravenous and oral hydration. Once volume repletion is achieved,
loop diuretics are used for calcium excretion. Bisphosphonates, calcitonin, and steroids are other adjuncts, depending
on the response to treatment and the primary cause of the
elevated calcium concentration. Please refer to Chapter 201
for further details on hypercalcemia.
Acute blood hyperviscosity results from elevations of
serum proteins (hyperviscosity syndrome) or WBCs (hyperleukocytosis) in the blood circulation. Leukocytosis and leukostasis (Fig. 203.7) have mortality rates that range from 20%
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White Blood Cell Disorders
BOX 203.5 Hyperviscosity Syndrome
Presentation and Management
BOX 203.6 Hyperleukocytosis Syndrome
Presentation and Management
History
• Waldenström macroglobulinemia
• Multiple myeloma
• Sjögren syndrome
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Cryoglobulinemia
• Diabetes
• Human immunodeficiency virus infection
History
• Leukemia
– More common in AML and ALL
• Dyspnea
• Chest pain
• Neurologic symptoms
• Malaise
Physical: Triad of Symptoms
• Bleeding
• Visual disturbances
• Focal neurologic signs
– Vertigo
– Paresthesias
– Headaches
– Ataxia
Diagnosis
• Clinical
• Increased viscosity
– More than 4 cp (normal, 1.4 to 1.8 cp)
Management
• Supportive
– Judicious fluid resuscitation
– Correction of electrolyte derangements
– Antibiotics if underlying infection
• Plasma exchange
– Indication: seizure or coma
– Phlebotomize 1 to 2 units
– Replace volume with normal saline solution
• Plasmapheresis
– Establish central venous access
– Contact plasmapheresis team
• Chemotherapy for underlying malignant disease
Adapted from Adams BD, Baker R, Lopez JA, Spencer S. Myeloproliferative disorders and hyperviscosity syndrome. Emerg Med Clin North Am
2009;27:459-76.
to 40%, and these conditions therefore represent an emergency diagnosis.17 Boxes 203.5 and 203.6 outline the presentations and management of both conditions.
NEXT STEPS OF CARE: ADMISSIONS
(INPATIENT AND OUTPATIENT)
Overall patient disposition is based on clinical assessment, the
ability to follow-up with a primary care physician or oncologist, and the patient’s home environment.
A patient with a new diagnosis of malignant disease may
require an in-depth work-up that may be more rapidly facilitated by admission and coordination between oncology staff
and primary care physicians.
For patients with a known cancer diagnosis, positive pressure isolation rooms should be considered in patients with
Physical
• Respiratory distress
• Altered mental status
• Focal neurologic deficits
• Limb ischemia
Diagnosis
• Laboratory values
– Leukostasis: WBC > 100 × 109/L (AML), WBC > 400 ×
109/L (ALL)
• Chest radiography
– Normal, interstitial or alveolar infiltrates, pleural effusions
Management
• Leukapheresis
– Central venous access
• Hydroxyurea
• Intravenous hydration
Adapted from Adams BD, Baker R, Lopez JA, Spencer S. Myeloproliferative disorders and hyperviscosity syndrome. Emerg Med Clin North Am
2009;27:459-76.
ALL, Acute lymphocytic leukemia; AML, acute myelogenous leukemia;
WBC, white blood cell.
significant neutropenia, in bone marrow transplant recipients,
or in patients with other high-risk immunocompromised states
(after intensive chemotherapy or solid organ transplantation).
Intensive care monitoring should be reserved for patients who
are critically ill, usually from complications of immunocompromise or chemotherapy.
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Nau KM, Lewis WD. Multiple myeloma: diagnosis and treatment. Am Fam Physician
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