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34 Cards in this Set

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What is a differential WBC count?
A quantification of the RELATIVE numbers of different types of leukocytes present in the blood

Supplement to, NOT a substitute for, the critical exam of a blood smear by the physician
The differential WBC count, in combination with the total WBC, allows calculation of...?
ABSOLUTE numbers of the WBC present in peripheral blood
What is leukocytosis?
WBC count > 12000/mm3

Can be caused by many pahysiologic and pathologic conditions

Most cases due to increase in PMNs, although increases in other WBCs can also be responsible
Common causes of leukocytosis?
1. Severe exercise or stress
2. Drugs - steroids, epi, drug rxns
3. Acute inflamm states
-- acute infection (bacteria, some viruses/parasites)
-- acute gouty arthritis
-- IBD
4. Chronic inflamm states
-- chronic infections (TB, fungal)
-- autoimmune d/o's (RA)
5. Tissue necrosis
-- MI
-- crush injuries
6. Metabolic d/o's
-- diabetic acidosis
-- uremia
7. hemorrhage
8. hematopoietic malignancies
-- leukemias
-- lymphomas
9. other tumors
10. surgical stress
Three pathophysiologic mechs of leukopenia?
1. decreased production
2. decreased survival
-- increased utilization
-- autoimmune destruction
3. redistribution
Examples of decreased production WBCs leading to leukopenia?
1. Aplastic anemia

2. Vitamin B12 or folate deficiency

3. Myelodysplastic syndromes

4. BM invasion by cancer
Examples of decreased survival of WBCs leading to leukopenia?
1. Felty's syndrome
-- in pts w/ RA

2. other autoimmune d/o's
Examples of redistribution of WBCs leading to leukopenia?
1. splenomegaly

2. acute infection in which most WBC migrate to the infected area
Pertinent clinical hx of pt w/ abnormal WBC?
--symptoms, how long?
--fever, wt loss, frequent infections, bleeding
--hx of recent acute illness
--family hx of cancer
--hx of chronic illness
--hx of exposure to toxic or carcinogenic agents
Pertinent PE of pt w/ abnormal WBC?
-- patient appear acute or chronically ill?
-- lymphadenopathy
-- hepatomegaly
-- splenomegaly
-- easy bruising, other signs of bleeding
-- signs of infection
-- signs of organ infilt by a tumor sich as gingival hypertrophy or soft tissue masses
Basic Laboratory Tests
1. Total WBC, Hb, platelet count
-- isolated WBC abnormality OR
-- Hb, platelets also abnorm

2. Differential WBC
-- any abnormally high/low
-- immature cells
-- any undiff blasts

3. Review smear yourself
Other tests utilized in the eval of abnormal WBC?
1, cytochemical stains for classif of leukemias

2. immunophenotypic analysis to determine cell lineage
-- myeloid
-- lymphocytic, etc

3. cytogenetic analysis of hematopoietic cells
-- estab dx of some leukemias and to determine their prognosis
Acute leukemia
Untreated survival: days of wks

Duration of symptoms at presentation: days of weeks

Condition of pt at presentation: usually very ill

Presence of signs of BM failure: usually high

Proportion of blasts in peripheral circulation: usually high

Leukemia infiltration of non-reticuloendothelial organs: frequent

Maturation arrest: Yes
Chronic leukemia
Survival untreated: months or yrs

Duration of symptoms at presentation: months or years

Condition of pt at presentation: few symptoms, sometimes asymptomatic

Presence of signs of BM failure: unusual

Proportion of blasts in peripheral circulation: low

Leukemia infiltration of non-reticuloendothelial organs: unusual

Maturation arrest: NO
What are the chronic leukemias?
Chronic lymphocytic leukemia (CLL)

Chronic myelocytic leukemia (CML)
Chronic lymphocytic leukemia (CLL) incidence?
Most common leukemia in the Western Hemisphere

More frequent in elderly population and in males
CLL onset?
Insidious

As many as 1/3 are diagnosed incidentally or during routine exams
CLL symptoms?
malaise
fever
lymphadenopathy
night sweats
weight loss
occasionally infection or autoimmune phenomena
CLL PE?
Normal to...

Hepatosplenomegaly
Lymphadenopathy
Signs of anemia
CLL treatment?
Incurable

Cryotherapy is given for palliation of systemic symptoms, lymphadenopathy, or signs of BM destruction

Important component of treatment is early dx and treatment of infections since pts prone to develop serious infections duto to hypogammaglobulinemia
CLL median survival?
measured in years

depends on stage at diagnosis
Chronic myelocytic leukemia (CML) symptoms?
-- Many are asymptomatic at diagnosis

-- May present w/ LUQ pain or early satiety due to splenomegaly

Other symptoms:
weight loss
fever
night sweats
CML PE?
usually unremarkable except for splenomegaly
When is CML diagnosis suspected?
Patient presencts w/ leukocytosis in which all stages of granulocyte development are present in peripheral blood
Other CML findings?
splenomegaly
thrombycytosis
eosinophilia and/or basophilia
decreased leukocyte alkaline phosphatase (LAP) score
Also assoc w/ which chromosomal abnormality?
Philadelphia chromosome
t(9;22)
Clinical course of CML?
Chronic phase:
-- 3-4 years
-- asymptomatic

Accelerated phase:
-- systemic symptoms
-- increased WBC count despite therapy
-- increased basophilia, eosinophilia
-- increase proportion of blasts and immature cells in circ and BM

Blast crisis:
-- indistinguishable from acute leukemia
-- response to treatment is worse than acute
-- patients usually die in matter of weeks
CML treatment?
1. BM transplantation -- ONLY curative treatment
-- mostly used in younger pts w/o major comorbid illness, espec if they have HLA compatible sibling

2. Interferon + cytarabine (ara-c)
-- older pts or pts that lack suitable donors

3. hydroxyurea
-- only controls WBC count and does not delay onset blast crisis

4. imatinib mesylate
-- inhib bcr-abl tyrosine kinase, the constitutive abnormal gene product of the Philadelphia chromosome
Leukemoid rxns vs CML?
Leukemoid rxns can be confused w/ CML

Leukemoid rxn is extremely high WBC count that can mimic leukemia

Leukemoid rxns typically consist of mature PMNs, the majority of which are banded or earlier forms
-- platelets may be increased, but rarely more than 60K
-- basophilia and eosinophilia are ABSENT
-- LAP is normal or increased
-- BM shown myeloid hyperplasia w/o other abnormalities
Symptoms of acute leukemias?
Manifestations of BM failure including:
easy fatiguability
easy bruising or bleeding from mucosal surfaces
fever
infection
anemia
thrombocytopenia
decrease of fxnal PMNs

Bone pain and arthralgia may be also seen, espec in young patients
Physical findings of acute leukemias?
Minimal symptoms:
- pallor
- increased
- ecchymosis
- petechiae
- retinal hemorrhages

Monocytic leukemias:
- gingival hypertrophy
- skin and tissue infiltration

Hepatomegaly and lymphadenopathy can be seen occasionally at diagnosis, especially in acute LYMPHOCYTIC leukemias
Lab abnormalities of acute leukemias?
Most present w/ pancytopenia

Small proportion present w/ WBC of 100,000
-- increased risk of leukostasis due to impedence of blood flow from intravascular clumping of blood
-- can manifest as mental changes, cranial nerve palsies, dyspnea, or respiratory failure due to thrombi in circulation
How do we diagnose acute leukemias?
-- Bone marrow aspirate and biopsy exam
-- cytochemistry
-- immunotyping by fluoresce activated cell sorting using monoclonal Ab directed at leukemia-specific Ag
-- cytogenetic analysis of the blood or bone marrow at dx
Treatment for acute leukemias?
1. aggressive chemo to clear BM of blasts and restore normal hematopoiesis
-- called induction chemo
-- even when pts attain complete remission, further chemo necessary to prevent recurrence (consolidation chemo)

ALL:
-- benefit from low dose chemo given p.o. for prolonged periods of time (1 or 2 yrs), called "maintenance chemo"
-- also require prophylactic chemo or radiotherapy of the CNS since this can be a "sanctuary" of the disease that can contribute to relapse
-- 30-35% can be cured w/ conventional chemo

AML:
-- 25% can be cured w/ conventional chemo

Once patients relapse after chemo, the only curative treatment is a BM transplant (in selected patient group)