Leukocytosis (Small Group Session 25) Flashcards
Describe what is meant by a “shift to the left”: orderly and not orderly.
Left shift - mobilization of neutrophils often accompanied by increased number and and proportion of immature blood neutrophils (bands, sometimes metamyelocytes)
“Orderly” shift - all cell lines increase proportionally ex. greater increase in neutrophils than basophils, response from immature cell lines is less extensive than mature cells, associated with reactive causes
“Disorderly” shift - disproportionate increases in cell lines ex. immature cell increaese will be higher than the neutrophils, associated with neoplastic causes
What are some causes of reactive neutrophilia?
- Infections (acute or chronic)
- Inflammation or tissue necrosis (acute or chronic)
- Physical stimuli (acute) ex. cold, heat, exercise, pain, labor
- Emotional stimuli (acute) ex. panic, rage
- Drugs, hormones toxins (acute or chronic)
- Malignancies (chronic)
- Metabolic and endocrine disorders (chronic)
- Asplenia
A 17 yr old M with uticaria and an acute asthma attack with wheezing and SOB. He is treated with a broncodilator and prednisone and several days later he is seen in your office feeling much better. His CBC shows the following: Hb 150g/L, platelets 300 x 109/L, WBC 16 x 109/L (differential - neutrophils 14.5 x 109/L, bands 0.36 x 109/L, metamyelocytes 0.16 x 109/L and lymphocytes 0.16 x 109/L). What is the mechanism of his neutrophilia?
A. Increase marrow release of neutrophils
B. Decreased splenic pooling
C. Demargination
D. Increased production of neutrophils
E. All of the above
F. A and C
F. A and C
This is a reactive neutrophilia. In addition, prednisone can increase marrow release of neutrophils and demargination.
How do glucocorticoids ex. prednisone predispose patients to infection and how do these drugs effect leukocytes?
Glucocorticoid-Induced Neutrophilia and other WBC changes
Quantitative WBC changes
- Neutrophilia
- Increase release of neutrophils from marrow
- Demargination
- Decrease egress of neutrophils from circulation into tissues (impaired chemotaxis)
- Lymphoneia, eosinopenia, monocytopenia
* Increased destruction of these WBCs
Qualitative WBC changes
- Decreased immunoglobulin (IgG) synthesis
- Imparied antigen presentation
- Impaired chemotaxis by phagocytic cells
- Decreased Fc receptor expression by phagocytic cells
- Impaired phagocytosis
The combined effect is immune suppression which results in a predisoposition for infection.
What are the 4 Myeloproliferative Disorders?
- Chonic Myelogenous Leukemia (CML)
- Primary Myelofibrosis (PMF)
- Polycythemia Vera (PV)
- Essential Thrombocythemia (ET)
68 M, history of diabetes, peripheral vascular disease, is admitted to MTU with a diagnosis of osteomyelitis of his right toe. A routine CBC reveals the following: Hb 140, platelets 277, WBC 33.5 (differential: neutrophils 25.5, bands 1.7, metamyelocytes 1.0, myelocytes 1.3, basophils 0.7, and lymphocytes 2.3. He is started on antibiotic therapy. What is the underlying cuase of his neutrophilia?
A. Acute osteomyelitis
B. Chronic osteomyelitis
C. Acute myeloid leukemia
D. Chronic myelogenous leukemia
E. A and D
F. B and D
E. A and D
The underlying cause of the neutrophilia in this case is the acute osteomyelitis and chronic myelogenous leukemia.
A 55 year old man presents to you with easy fatigability and weight loss of 15 pounds over the last 6 months. Results of the CBC available so far reveal hemoglobin 125 g/L, WBC 25 x 109/L with 13% lymphocytes (25-33%), 3% eosinophils (1-3%), 2% basophils (0-0.75%), and 6% monocytes (3-7%). Platelet count is 525 x 109/L. Physical exam reveals an enlarged spleen 3 cm below the costal margin.
A white blood cell differential is ordered and you are given the following results:
1% Promyelocytes
5% Myelocytes
6% Metamyelocytes
4% Bands (3-5%)
60% Neutrophils (54-62%)
2% Basophils (0-0.75%)
How would you confirm the diagnosis?
The diagnosis would be confirmed by RT-PCR. Other testing modalities available include standard cytogenetic analysis and FISH.
- Detection of the Ph chromosome or its products (BCR-ABL fusion mRNA and Bcr-Abl protein) is required for the diagnosis of CML
CML Pathophysiology
- Philadelphia chromosome
- Translocation between chromosomes 9 and 22
- The c-abl proto-oncogene is translocated from chromosome 9 to “breakpoint cluster region” (bcr) of chromosome 22 to produce bcr-abl fusion gene, an active tyrosine kinase
A 55 year old man presents to you with easy fatigability and weight loss of 15 pounds over the last 6 months. Results of the CBC available so far reveal hemoglobin 125 g/L, WBC 25 x 109/L with 13% lymphocytes (25-33%), 3% eosinophils (1-3%), 2% basophils (0-0.75%), and 6% monocytes (3-7%). Platelet count is 525 x 109/L. Physical exam reveals an enlarged spleen 3 cm below the costal margin.
A white blood cell differential is ordered and you are given the following results:
1% Promyelocytes
5% Myelocytes
6% Metamyelocytes
4% Bands (3-5%)
60% Neutrophils (54-62%)
2% Basophils (0-0.75%)
What is your first line and second line therapy for this patient?
This patient has CML. The first line treatment is a tyrosine kinase inhibitor (Imatinib = Glivec). Second line therapy is an allogenic HSCT.
What are the clinical features of Chronic Myeloid Leukemia (CML)?
- 20-50% asymptomatic
- Chronic, accelerated and blast phase (defined by marrow blast %)
- 85% present in chronic phase, of which 20-50% have no physical symptoms
- Anemia
- Priapism
- B symptoms
- Bleeding and bruising (platelet dysfunction)
- Splenomegaly (50-90%)
- Hepatomegaly (50%)
- Boney pain
- Sternal tenderness, low back pain
- Acute gouty arthritis
- Platelet dysfunction; purpura common, bleeding increased in blast phase
- DIC
- No lymphadenopathy
What is the median age of presentation for CML?
The median age of presentation for CML is 50-60 years
- Accounts for 15-20% of adult leukemias, 2% of childhood leukemias
A 67 yr old F is admitted to the ICU with a 24 hr history of fever and rigors and has hypotension (blood pressure 80/50). The pt also has a history of arthritis and has been on prednisone for the past 2 years. The CBC reveals a Hgb of 120 g/L, platelet count of 550 x 109/L with a differential of 70% neutrophils, 15% bands, 8% monocytes, 5% lymphocytes and 2% metamyelocytes.
What further investigation do you require?
Leukocyte Alkaline Phosphatase (LAP) - will differentiate a leukomoid reaction from CML
A 67 yr old F is admitted to the ICU with a 24 hr history of fever and rigors and has hypotension (blood pressure 80/50). The pt also has a history of arthritis and has been on prednisone for the past 2 years. The CBC reveals a Hgb of 120 g/L, platelet count of 550 x 109/L with a differential of 70% neutrophils, 15% bands, 8% monocytes, 5% lymphocytes and 2% metamyelocytes.
Describe the shift in the WBC differential.
This is an orderly left shift.
Compare and contrast a Leukemoid Reaction and Chronic Myeloid Leukemia.
- Differential
- Basophilia/Eosinophilia
- Myeloblasts
- Thrombocytosis
- Splenomegaly
- t(9;22)
Leukomoid Reaction
- Differential: Orderly
- Basophilia/Eosinophilia: Uncommon
- Myeloblasts: Uncommon
- Thrombocytosis: Yes
- Splenomegaly: Negative (may occur in some cases ex. EBV)
- t(9;22): Negative
Chronic Myeloid Leukemia
- Differential: Orderly
- Basophilia/Eosinophilia: Elevated
- Myeloblasts: Present
- Thrombocytosis: May develop as CML progresses
- Splenomegaly: Yes, extra medullary hematopoiesis
- t(9;22): Yes
What can be observed in this smear? What does this pattern of cells indicate?
This smear is from a patient with Chronic Myeloid Leukemia.
- Neutrophils
- Bands
- Basophils
- Myelocytes
- Metamyelocytes
Overall, a disoderly left shift is noted.
What phase of CML is indicated by this image? At this point, CML is at risk for transformation to ___ or ___.
This is a blast crisis. At this point, the CML may transform to AML or ALL or be biphenotypic. Without SCT or Imatinib median survival is 3-6 months.
