Hemo 1 Flashcards
Leukocytosis -
an increase in total circulating white blood cells
Neutrophilia (granulocytosis) -
bacterial infections
Lymphocytosis -
viral infections
Eosinophilia -
parasitic infections, allergic reactions
Leukemoid reaction -
an elevated white blood cell count that is a physiologic response to
stress or infection
Leukopenia –
a decrease in total circulating white blood cell count
Neutropenia –
antineoplastic therapy, drugs
Lymphopenia –
steroid therapy
Pancytopenia –
all cell lines affected – anemia, thrombocytopenia,
neutropenia
The terms agranulocytosis, (2) are
often used interchangeably
granulocytopenia and neutropenia
Normal adult peripheral white blood cell count
4,500 – 11,000 /mm3
Clinically relevant neutropenia –
Absolute Neutrophil Count (ANC) < 500 /mm3
Neutropenia
Susceptibility to
bacterial and fungal infections
Causes of Neutropenia
Decreased production
(4)
Drugs
Hematologic disease – cyclic neutropenia
Nutritional deficiency – B12, Folate
Myelophthisis
Causes of Neutropenia
Increased destruction -
autoimmune reactions
In severe neutropenia the signs of — may be absent
infection
WBC count
1,600 cells/ul (4,000 – 11,000)
Differential white blood cell count
Polys
4 % (45 – 78 %)
Differential white blood cell count
Lymphocytes
69 % (15 – 47 %)
Differential white blood cell count
Monocytes
27 % ( 0 - 12 %)
Differential white blood cell count
Eosinophils
0 % ( 0 – 7 %)
Differential white blood cell count
Basophils
0 % ( 0 – 2 %)
Absolute neutrophil count =
1,600 wbc/ul X 0.04 = 64 neutrophils/ul
Cyclic Neutropenia
Regular, periodic reductions in neutrophils
Cyclic Neutropenia
Symptoms greatest at nadir
– fever,
lymphadenopathy, malaise, pharyngitis,
ulcerations, periodontitis
Cyclic Neutropenia
Treatment -
supportive care, cytokine
therapy (G-CSF)
Leukemias -
the neoplastic cells are in the bone
marrow and blood
Lymphomas -
the neoplastic cells are in the
lymph nodes – (also extranodal sites)
Leukemia and Lymphoma describe the
tissue distribution of disease
Leukemia
Arises in
Spreads to
bone marrow
peripheral blood
Lymphoma
Arises in
Forms a
May eventually spread to
peripheral lymphoid tissue, usually in lymph nodes
discrete tissue mass
peripheral blood and bone marrow
Acute Leukemia
(4)
Abrupt, stormy onset
No maturation - precursor cells (blasts)
proliferate
Kills rapidly without treatment
Cure is possible
Chronic Leukemia
(4)
Insidious course
Maturation - mature cells proliferate
Often not treated unless symptomatic
Cannot be cured
Classification of Leukemias by Cell of
Origin and Clinical Course
(4)
Acute Lymphoblastic Leukemia
Acute Myelogenous Leukemia
Chronic Lymphocytic Leukemia
Chronic Myelogenous Leukemia
Cytopenias -
depression of normal bone marrow function
Bleeding –
petechiae, ecchymoses, epistaxis, gingival
hemorrhage due to thrombocytopenia
Fever -
infections due to absence of mature granulocytes
Fatigue -
anemia
Clinical Symptoms of Acute Leukemia
(4)
Cytopenias - depression of normal bone marrow function
Bleeding – petechiae, ecchymoses, epistaxis, gingival
hemorrhage due to thrombocytopenia
Fever - infections due to absence of mature granulocytes
Fatigue - anemia
Acute Lymphoblastic Leukemia
(3)
Lymphoblasts - immature precursor B or T lymphocytes
arrested at early stage of development
A disease of children
Good prognosis with aggressive chemotherapy
Acute Myeloblastic Leukemia
(4)
Myeloblasts – immature myeloid precursors (granulocytic,
monocytic, erythroid, megakaryocytic) with no terminal
myeloid differentiation
Adults
Prognosis – chemotherapy, bone marrow transplantation.
More difficult to treat than ALL.
Gingival enlargement in monocytic types of AML
Clinical Symptoms of Chronic Leukemia
(2)
Often clinically silent
Incidental leukocytosis on CBC
Chronic Myelogenous Leukemia
(6)
Adults
Insidious onset, slow progression
Philadelphia chromosome – t(9:22) bcr-abl fusion gene
Splenomegaly, fever, fatigue
Blast crisis
Bone marrow transplantation
Philadelphia Chromosome
(6)
Translocation t(9:22)
Proto-oncogene abl on long arm chromosome
9(q34)
Transposed to bcr region (breakpoint cluster
region) on chromosome 22(q11)
Results in bcr-abl fusion gene
Gene product is abnormal
bcr-abl tyrosine kinase
Induces cell proliferation
Chronic Lymphocytic Leukemia
(6)
Most common type of leukemia
Adults, often asymptomatic
Hypogammaglobulinemia – infections
Anti red cell autoantibodies – autoimmune hemolytic anemia
Anti platelet autoantibodies – autoimmune thrombocytopenia
Richter syndrome – may transform to high grade lymphoma
Clinical Presentation of Lymphoid Neoplasms:
Related to Anatomic Distribution
Lymphoma -
non-tender lymph node enlargement,
extra-nodal mass
Clinical Presentation of Lymphoid Neoplasms:
Related to Anatomic Distribution
Leukemia -
cytopenias due to suppression of
hematopoiesis
Clinical Presentation of Lymphoid Neoplasms:
Related to Anatomic Distribution
Plasma cell neoplasms -
bone pain, pathologic fracture
Lymphoma Classification:
“Malignant” Lymphoma
(2)
Hodgkin Lymphoma – HL
Non-Hodgkin Lymphoma - NHL
Clinical Presentation of NHL
(3)
Painless lymphadenopathy with firm,
enlarged, rubbery, freely movable,
non-tender lymph nodes
Generally involves multiple lymph
nodes in a non-contiguous pattern
Frequently involves extranodal sites
Most NHL arises within
lymph nodes –
70%
NHL may also arise extra-
nodally –
30%
Oral mucosal NHL is
extra-
nodal
All Lymphomas are Malignant
Degree of — varies
Low grade -
High grade -
aggressiveness
indolent, difficult to cure
aggressive, often curable
Burkitt Lymphoma – High Grade
(3)
“African Jaw Lymphoma”
B-Cell NHL
EBV association
MALT Lymphoma – Low Grade
(4)
Arises from Mucosal-
Associated Lymphoid Tissue
“MALT-oma” - mature B cells
Often indolent
Salivary glands, Sjogren
Syndrome
May transform to high grade
lymphoma
Burkitt Lymphoma
(3)
A sub-type of non-Hodgkin lymphoma (NHL)
A high grade B cell neoplasm, most rapidly-growing
human neoplasm
The endemic form has a predilection for jaws of children
Burkitt Lymphoma
Three clinical forms
Endemic (African)
Sporadic
HIV-associated
Burkitt Lymphoma
– association
Epstein Barr Virus
Association of Epstein-Barr Virus
(HHV-4 ) with Human Disease
(4)
- Infectious Mononucleosis
- Lymphomas – NHL and HL
e.g. Burkitt lymphoma (NHL) - Nasopharyngeal Carcinoma
- Oral Hairy Leukoplakia
Cytogenetics of
Burkitt Lymphoma
(4)
Translocations, t(8:14) is the most
common
c-myc proto-oncogene on
chromosome 8 has a role in cell
cycle progression
Immunoglobulin gene promoters
cause overexpression of c-myc
Overexpression of c-myc oncogene
promotes inappropriate cellular
proliferation
Oral Findings in Burkitt Lymphoma
(2)
Rapidly growing painless
swelling, producing
paresthesia, loose teeth
Rapid demise if untreated
Chemotherapy in Burkitt Lymphoma
(2)
High grade lymphoma - aggressive
Cures frequent with short-term, high-dose
chemotherapy
Three Examples of
Non-Hodgkin Lymphoma
(3)
Burkitt Lymphoma
Diffuse large cell lymphoma
MALT-oma
Hodgkin Lymphoma (HL)
The neoplastic cell:
Reed-Sternberg cell
The Reed-Sternberg Cell:
Neoplastic Cell in Hodgkin Lymphoma
(3)
A minor fraction of the
tumor mass
Most are of B cell origin
Bilobate nucleus with large
inclusion-like nucleoli -
“owl-eye” cell
General Characteristics of
Hodgkin Lymphoma
(4)
Bimodal age distribution - young adults, older adults
Painless lymphadenopathy
Constitutional symptoms variable
Association with Epstein Barr virus
Constitutional symptoms variable
(4)
Fever – Pel-Ebstein fever
Night sweats
Weight loss
Generalized pruritus
Spread of Hodgkin Lymphoma
Uniform, predictable pattern of spread from one lymph node region to the next
Staging of Non-Hodgkin Lymphoma
Characterizes extent of disease
* Stage I
– Single lymph node region
Staging of Non-Hodgkin Lymphoma
Characterizes extent of disease
* Stage II
(2)
– Multiple lymph node regions
– Same side of diaphram
Staging of Non-Hodgkin Lymphoma
Characterizes extent of disease
* Stage III
(2)
– Multiple lymph node regions
– Both sides of diaphragm
Staging of Non-Hodgkin Lymphoma
Characterizes extent of disease
Stage IV
– Disseminated disease
“B” Symptoms for Staging of Non-Hodgkin Lymphoma
(3)
Recurrent, unexplained fevers
Night sweats
Unintended weight loss
Treatment of Non-Hodgkin Lymphoma
Low-grade lymphomas -
treat only if symptomatic
Treatment of Non-Hodgkin Lymphoma
High-grade lymphomas
(2)
Localized stage - RT
Advanced stage – CT or combination CT/RT
Staging of Hodgkin Lymphoma –
Characterizes the Extent of Disease
Stage I -
single lymph node region
Staging of Hodgkin Lymphoma –
Characterizes the Extent of Disease
Stage II -
multiple lymph node regions on same side of diaphragm
Staging of Hodgkin Lymphoma –
Characterizes the Extent of Disease
Stage III -
multiple lymph node regions on both sides of diaphragm
Staging of Hodgkin Lymphoma –
Characterizes the Extent of Disease
Stage IV -
disseminated disease
Treatment of Hodgkin Lymphoma
(4)
Stage determines treatment protocol
Localized (Stage I) - local radiation therapy
Disseminated (Stage IV) – chemotherapy
Risk of second cancers
Prognosis of Hodgkin Lymphoma
(3)
Stage - most important
Histologic sub-type - least important
Curable - Stage I – 90% cure rate
Multiple Myeloma
(4)
Older adults
Disseminated neoplasm of terminally-differentiated B
lymphocytes (plasma cells)
Multifocal lytic bone lesions, hypercalcemia, bone pain
Myelophthisic anemia, predisposition to infections
Complications:
Multiple Myeloma
(3)
Renal failure
Infection
Anemia
Laboratory Findings:
Multiple Myeloma
(7)
Elevated serum calcium, protein, immunoglobulins
Elevated erythrocyte sedimentation rate (ESR)
Rouleaux formation
Monoclonal gammopathy - M-spike
Bence-Jones proteinuria - immunoglobulin light chains
Lytic lesions, loose teeth, pain, paresthesia,
pathologic fracture
Macroglossia - amyloidosis
Bleeding Time Test
Bleeding Time Test
(4)
Clinical assessment for adequate number and function of platelets.
The bleeding time test represents the time taken for a standardized skin puncture to stop
bleeding
The normal range depends on the actual method used and varies from 2 to 9 minutes
It is abnormal when there are congenital or acquired platelet defects
It is abnormal when there are congenital or acquired platelet defects
(2)
Drugs – ASA, NSAIDS
Von Willebrand Disease
Platelet Disorders
(3)
Thrombocytopenia - decrease
Thrombocytosis - increase
Functional defects
Platelet Functional Defects -
Thrombasthenia
Aspirin -
inhibits aggregation for lifetime of platelet (8-10d) (irreversible)
Platelet Functional Defects -
Thrombasthenia
NSAIDs -
inhibits aggregation until drug eliminated (reversible)
Platelet Functional Defects -
Thrombasthenia
Von Willebrand Disease -
compound defect involving platelet function and
coagulation pathway
Normal platelet count with increased bleeding time
Petechiae -
pinpoint hemorrhages
Purpura -
petechiae become confluent
Ecchymosis -
purpurae become confluent
Hematoma –
cavity
Thrombocytopenia
Normal platelet count -
Thrombocytopenia -
150,000 to 450,000 /mm3
< 100,000 /mm3
Causes of Thrombocytopenia
(4)
Decreased production - aplastic anemia
Increased destruction – immunologic destruction
Sequestration in spleen – splenomegaly
Dilution - massive transfusion
Immune Thrombocytopenic
Purpura (ITP)
Autoimmune disease–
Treatment with (2)
antiplatelet autoantibodies
produce thrombocytopenia
steroids, splenectomy
mmune Thrombocytopenic Purpura
(ITP) Platelets =
7, 000 /ml
Thrombocytosis
(Thrombocythemia)
Primary thrombocytosis (essential) - hematopoietic stem cell disorder
(1)
Increased numbers of megakaryocytes producing dysfunctional platelets
Thrombocytosis
(Thrombocythemia)
Reactive thrombocytosis
(2)
Asplenia
Inflammatory disorders