PANCE Blueprint Hematology (5%)

Leukopenia

Patient will present as → a 68-year-old woman presents to the emergency department due to fatigue, malaise, and subjective fever. Her symptoms began approximately 1 week ago. Medical history is significant for small cell lung cancer recently treated with doxorubicin plus cyclophosphamide and etoposide. Her temperature is 102°F (38.9°C) and blood pressure is 100/80 mmHg. A complete blood count with differential is remarkable for an absolute neutrophil count of 320 cells/mm3. She is admitted to the hospital and administered intravenous cefepime.

Leukopenia is a decrease in the total number of white blood cells (leukocytes) found in the blood, which places individuals at increased risk for infection

 There are five types of white blood cells (note: neutrophils, eosinophils, and basophils are all types of granulocytes).

  1. Neutrophils are the first responder of immune cells
  2. Eosinophils fight bacteria and parasites but also provoke allergy symptoms
  3. Basophils release histamine to mount a non-specific immune response
  4. Monocytes clean up dead cells
  5. Lymphocytes (T cells and B cells) defend against specific invaders
"We can use the mnemonic 'Never Let Mamma Eat Beans' to remember the names of the different leukocytes."

Terminology: 

  • Leukopenia: is a reduction in the circulating white blood cell (WBC) count. It is usually characterized by a reduced number of circulating neutrophils, although a reduced number of lymphocytes, monocytes, eosinophils, or basophils may also contribute. Thus, immune function can be decreased.
  • Neutropenia, a subtype of leukopenia, refers to a decrease in the number of circulating neutrophil granulocytes, the most abundant white blood cells (40-70%). The terms leukopenia and neutropenia may occasionally be used interchangeably.
    • Agranulocytosis is a complete absence of neutrophilsdrugs that cause this include clozapine, propylthiouracil, penicillin G, methimazole, and dapsone.
  • Lymphocytopenia is a decrease in the number of circulating lymphocytes. The most common cause of lymphopenia worldwide is protein-calorie malnutrition.
  • Monocytopenia is a reduction in blood monocyte count. The major causes of this condition include use of myelotoxic drugs, acute infectious stress, aplastic anemia, hairy cell leukemia, and myeloid leukemia.
  • Granulocytopenia is a reduced number of neutrophils, eosinophils, and basophils.

Low white cell count may be due to acute viral infections, such as a cold or influenza.

  • Associated with chemotherapy, radiation therapy, myelofibrosis, aplastic anemia, stem cell transplant, bone marrow transplant, HIV, AIDS, and steroid use.
  • Medical conditions such as systemic lupus erythematosus, Hodgkin's lymphoma, some types of cancer, etc.
  • Medications such as clozapine, bupropion, minocycline, valproic acid, lamotrigine, metronidazole, immunosuppressive drugs, and interferons used to treat MS.
The normal range for the white blood cell (WBC) count in adults is 4400 to 11,000 cells/microL

The absolute neutrophil count (ANC) is the number of neutrophils plus bands (does not include metamyelocytes and less mature forms). Mature neutrophils are also called polymorphonuclear cells (PMNs).

ANC = WBC (cells/microL) x percent (PMNs + bands) ÷ 100

Leukopenia can be identified with a complete blood count + blood smear

  • Leukopenia is a reduced total WBC count of <4400 cells/microL
  • Neutropenia is defined as an absolute neutrophil count (ANC) of less than <1500 cells/microL
  • Agranulocytosis is defined as an ANC <200 cells/microL
  • Monocytopenia is a reduction in blood monocyte count to < 500/microL
  • Lymphocytopenia is a reduction in blood lymphocytes of < 1000/mcL

Additional tests

  • Complete metabolic panel
  • Blood cultures
  • Urine culture
  • Culture of sites concerning for infection
  • Radiologic studies and CT scan

Treatment will be guided by the cause

  • Discontinue causative agents
  • Antibiotics in case of neutropenic fever
  • Referral to hematology and/or specialized testing may be useful for patients in whom the cause for neutropenia has not been established by the initial evaluation

Question 1
Of the different types of leukopenia, which one involves the most abundant white blood cells?
A
Basopenia
Hint:
See C for explanation
B
Lymphocytopenia
Hint:
See C for explanation
C
Neutropenia
D
Monocytopenia
Hint:
See C for explanation
Question 1 Explanation: 
Neutropenia, a subtype of leukopenia, refers to a decrease in the number of circulating neutrophil granulocytes. Neutrophils are the most abundant WBCs in peripheral blood (typically 40 to 70 percent). For this reason, the terms leukopenia and neutropenia may occasionally be used interchangeably. Neutropenia is sometimes accompanied by monocytopenia and lymphocytopenia, which cause additional immune deficits.
Question 2
A 15-year-old male is admitted to the hospital for treatment of acute lymphoblastic leukemia. During his hospital course, he developed a fever of 102.2 F. A CBC demonstrates a leukocyte count of <500 cells/microL. Which of the following is the most appropriate initial management of this patient?
A
Granulocyte colony-stimulating factor (G-CSF)
Hint:
While G-CSF is often given to patients to increase the neutrophil count, it has not been proven to improve outcomes in patients with neutropenic fever.
B
IV ceftazidime
C
Oral doxycycline
Hint:
Oral doxycycline monotherapy is insufficient empiric coverage in patients with neutropenic fever.
D
Strict quarantine and handwashing
Hint:
While handwashing is expected universally, and isolation is appropriate in certain situations, strict quarantine is not a proven intervention for neutropenic fever.
Question 2 Explanation: 
The Infectious Diseases Society of America defines fever in neutropenic patients as a single oral temperature of ≥38.3°C (101°F) or a temperature of ≥38.0°C (100.4°F) sustained over a one-hour period. This patient has neutropenic fever in the hospital environment. Treatment with IV ceftazidime is the most appropriate treatment.
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References: Merck Manual · UpToDate

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