WBC abnormalities Flashcards
- WBC > 10, 000
- In response to acute infection, trauma or inflammation
- WBCs release the colony-stimulating factor (CSF) to increase WBC production in the bone marrow
- Increase in one of the five types of WBC (neutrophilic, lymphcytic…)
Leukocytosis
- WBC <4,000
* Increased risk for infection
Leukopenia
Leukopenia is due to
- Viral infections
- Overwhelming bacterial infections (WBC consumption> production)
- Bone marrow disorders
- Certain drugs
specific reax of WBC
Leukoerythroblastic rxn
Leukamoid rxns
specific reaction of WBC with presence of nucleated RBC and immature neutrophils
Leukoerythroblastic reaction
What does the leukoerythroblastic reaction indicate?
severe disruption of marrow (common in myelofibrosis) and possible extramedullary hematopoiesis (secondary to metastatic cancer)
leukoerythroblastic reaction is secondary to what
tumor, fibrosis, lymphoma or leukemia
leukamoid reactions where WBC > 50 x 10^9/L indicate presence of immature forms such as
- Blast form
- Myelocytes
- Promyelocytes
- Metamyelocytes
It is the reactive leukocytosis seen in leukemia
Leukamoid reaction
benign or malignant condition
neutrophilia or the abnormally high neutrophil count (> 7.0 - 8.0 x 109 /L or 7000- 8000/uL) is associated with
• Acute inflammation • Acute stress • Myelocytic leukemia • Eclampsia • Gout • Autoimmune disease (Rheumatoid arthritis and Thyroiditis) • Trauma (Infection, inflammation, malignancy)
neutropenia or an abnormally low neutrophil count (ANC: <1500/uL) is associated with
• Aplastic anemia (low cell lines) • Widespread severe bacterial infection • Chemotherapy • Radiation therapy/ exposure • Viral infection • Increased risk of life-threatening bacterial infection
What happens if ANC 500 - 1000?
increased risk of
infection from exposure
What happens if ANC < 500?
increased risk of infection from host organisms/
normal flora
Causes of neutrophilia
- due to acute shift from marginating to circulating pool
- due to chronic stimulation (excess cytokine stimulates proliferative pool)
causes of neutrophilia due to chronic stimulation
- Infection
- Chemotherapy recovery
- Down’s Syndrome
- Myeloprliferative disorders
- Pregnancy or eclampsia
- Marrow metastases
T or F: neutropenia is the most common cause of leukopenia
true
extreme neutropenia (<0.5 x10^9/L)
agranulocytosis
Causes of neutropenia
(Inherited vs. acquired)
- Decreased neutrophil production
- Increased neutrophil destruction
- Sequestration
- Pseudoneutropenia
[Causes of neutropenia] Examples of inherited causes of decreased neutrophil production
• Defective stem cell development - Reticular dysgenesis - Cyclic neutropenia - Infantile agranulocytosis - Fanconi’s syndrome • Genetic disorders of IS • Disorders of cellular development - Chediak-Higashi syndrome - Lazy Leukocyte syndrome
[Causes of neutropenia] Examples of acquired causes of decreased neutrophil production
• Chemical Toxicity - Ionizing Radiation - Benzene • Marrow replacement • Nutritional deficiency -Vitamin B12, B9 (Folate) • Cytotoxic Drugs
[Causes of neutropenia]
What are the immune reactions involved in increased neutrophil destruction?
• Isoimmune: transplacental transfer of maternal IgG
• Autoimmune
• Drug-induced
- Immunologic neutropenia: drug and neutrophil surface protein form an antigenic complex; neutrophils are destroyed by complement or the clumps of neutrophils are removed from the circulation or sequestered in the lungs, spleen, etc.
[Causes of neutropenia]
Sequestration indicates a shift to what pool
marginal pool (Neutrophils are removed from circulation and are redistributed within the body)
[Causes of neutropenia] It is the transient reduction in count involving neutrophil agglutination due to edta and antipsychotic medications
pseudoneutrophenia
What are qualitative abnormalities in WBC?
Morphological alterations or toxic changes in response to stress, infection, or inflammation
• Pelger-Huët Anomaly
• Pseudo-Pelger-Huët Anomaly
Qualitative abnormalities seen in neutrophilia (shift to the left)
- Presence of increased numbers of immature/ younger/precursor/less differentiated granulocyte neutrophils in the peripheral blood
- Reflects early or premature release of myeloid cells from the bone marrow, the site where neutrophils are generated
conditions where qualitative abnormalities seen in neutrophilia (shift to the left)
• Found in:
- Normal in pregnancy or neonate
- Infections
- Bone marrow fibrosis
- Bone marrow infiltration by malignancies
Qualitative abnormalities in WBC also indicate
- Evidence of maturation abnormalities
- Alterations in functional activity
- Degenerative changes
What is the best
indicator of severity of infection?
Ratio of non-segmented and segmented neutrophils
Pelger-Huët Anomaly shows neutrophils with
uniformly sized round or bilobed nuclei (due to failure to segment)
an autosomal dominant inherited disorder with no clinical effect
Pelger-Huët Anomaly
*may be misinterpreted as shift to left
Pseudo-Pelger-Huët Anomaly morphology
Bilobed neutrophils with more condensed chromatin
Pseudo-Pelger-Huët Anomaly are found in
- Myelodysplastic syndromes
- Idiopathic myelofibrosis
- Chronic leukemia
- Drug Therapy
- Infections (Malaria)
Cytoplasmic abnormalities of neutrophils
- Toxic granules
- Dohle bodies
- May-Heggelin anomaly
- Vacuolation
- Degranulation
- Pseudopods
- Auer rods
- Swelling
morphology of toxic granules
- Altered primary granules through simulation of antigens
- Large, dark blue-back granules
- Clustering within the cell
[Cytoplasmic abnormalities] Transient cytoplasmic inclusions consisting of rRNA in parallel rows which are pale blue, round or elongated bodies, 1 – 5 μm located near cell membranes
Dohle bodies
[Cytoplasmic abnormalities] Dohle bodies are found in
segmented and band neutrophils associated with a wider range of conditions
[Cytoplasmic abnormalities] An inherited autosomal dominant condition wherein large pale basophilic Dohle-like inclusion bodies primarily
in neutrophils
May-Heggelin anomaly
- asymptomatic
- decreased platelet counts = bleeding
[Cytoplasmic abnormalities] autophagocytosis in cytoplasmic vacuolation is brought upon by
- Sulfonamides and chloroquine (for malaria)
- Prolonged storage of cells
- Small and evenly distributed vacuoles
- Degranulation on exposure to toxins and high dose radiation
[Cytoplasmic abnormalities] Phagocytosis of ECM seen in cytoplasmic vaculation is seen in
sepsis; associated with toxic granules (large and unevenly distributed vacuoles)
[Cytoplasmic abnormalities] These are granule-free protrusions of cytoplasm indicating sluggish neutrophil locomotion
Pseudopods
*artifactual due to prolonged storage in EDTA; rare
[Cytoplasmic abnormalities] These are small azurophil rods in the cytoplasm of myeloblasts and promyelocytes sometimes found in mature neutrophils
auer rods
*AML and myelodisplastic syndrome
Nuclear abnormalities of wbc
• Pyknotic and/or necrotic nuclei • Hypersegmentation • Nuclear projections • Ring forms
[Nuclear abnormalities of wbc] seen in long term infections; normal-large size with increased % of neutrophils with 5-6 lobes of >3% neutrophils
Hypersegmented nuclei
Hypersegmented nuclei are found in
- Megaloblastic anemia
- Chronic infection
- Iron deficiency
- Liver disease
- Uremia
- Hereditary
[Nuclear abnormalities of wbc] shrunken and dense nuclei found in sepsis, AML or poor staining/prep
Pyknotic nuclei
[Nuclear abnormalities of wbc] hairlike projection with detached nuclear material in cytoplasm which are seen in band forms found in inner side of the band form, facing the centriole
Toxic nuclear projections
*irregular staining inside the nucleus)
Toxic nuclear projections are seen in
- Metastatic carcinoma
- Irradiation
- Dysgranulopoiesis
- Patients on anti-cancer chemotherapy
- HIV
[Nuclear abnormalities of wbc] nucleus ring or doughnut shaped found in toxic and malignant myeloproliferative states, early infxnss, AML, MA
Ringed nuclei
A morphological abnormality which is a rare fetal hereditary disorder found in children making them susceptible to infxns wherein neutrophils, monocytes, and lymphocytes are affected with large irregular granules
Chediak-Higashi Syndrome
*primarily due to neutrophil’s impaired function
Patients display these in Chediak-Higashi Syndrome
- Oculocutaneous albinism
- Photophobia
- Sun sensitivity
- Neuropathy (deranged senses)
- Pancytopenia (all blood cell lines are decreased)
- Infections (especially Staphylococcus aureus)
eosinophilia, an inherited autosomal dominant, malignant or reactive disorder is indicated by
> 0.7 x 10^9/L and eosinophil metamyelocyte in peripheral blood
(left shift)
Where is eosinophilia found?
• Reactive eosinophilia
- Parasitic or hypersensitivity disorders
- Suppress all helminths (Association of eosinophil count and parasitic death)
• Myeloproliferative disorders
• Acute Myeloid Leukemia
[Quantitative Abnormalities of eosinophil] persistent and extreme eosinophilia which is parasitic, allergic, malignant, idiopathic
Hypereosinophilic syndrome (>1.5 x 109/L)
Eosinopenia is indicated by _____ and is associated with production abnormalities
0.05x10^9/L
Where is eosinopenia usually seen?
• Acute bacterial infections
(Due to sequestration, margination and chemotaxis)
• ACTH administration
(Glucocorticoids, prostaglandins and epinephrine)
Qualitative eosinophil abnormalities
Degranulation (most prominent)
Vacuolation
Hypersegmentation
basophilia (>0.3 x10^9/L) is seen in
Conditions caused by eosinophilia since both of them are
controlled by T-lymphocytes and are of the same stem cell
line
Myeloproliferative disorders
Type I hypersensitivity reactions, long-term foreign antigen stimulation, hypothyroidism, ulcerative colitis, estrogen therapy
Reactive basophilia
Transient basophilia is usually seen in
newborns
Degranulation in basophil quali abno are due to
ingestion of fatty meal
antigen-related stimulation
Monocytosis or >0.9 x10^9/L monocytes accompanies what other quantitative abno?
neutrophilia due to common stem cell line
*may be reactive or malignant
Monocytosis is usually seen in
• Chronic bacterial infections
(Bacterial endocarditis, malaria, tuberculosis, typhoid)
• Chronic inflammation
(Collagen vascular diseases, Systematic Lupus Erythematosus, Rheumatoid Arthritis, ulcerative colitis, Sarcoidosis)
• Malignant – AML, CA, MDS, Hodgkin’s disease
• post splenectomy in chronic neutropenia
Monocytopenia or <0.03x10^9/L is seen in
Administration of glucocorticoids and overwhelming infections
T or F: qualitative abno in monocytes are responses to stimuli
true
(immature monocytes; transformation into histiocytes, macrophages [^cyto volume, ^dense granules, ^cyto vacuolation, IC debris, highly irreg cytoplasmic borders, reticular chromatin and visible nucleoli], alteration into long thin band-like shape)
These abnormalities are nonmalignant, reactive Disorders with self-limited lymphoproliferative responses
Lymphocyte abnormalities
Lymphocytosis in adults and children
- Adults: > 4.0 x109/L lymphocytes
* Children: > 9.0 x109/L lymphocytes
T or F: It is important to determine the relative increase in the number of circulating lymphocytes
false, absolute
Lymphocytosis can be seen in
Usually in viral infections, may also be seen in pertussis
Lymphopenia occurs in
• Immunodeficiency syndromes
(Congenital (e.g. DiGeorge syndrome) and Acquired conditions (e.g. AIDS))
• Corticosteroid therapy
• Neoplasia
(Hodgkin’s disease, Non-Hodgkin’s lymphoma and advanced carcinomas)
• Radiation therapy
• Chemotherapy
Lymphocyte abno where atypical, variant or Downey cell is seen with foamy, dense, vacuolated, basophilia (radial or peripheral) or irregular border (scalloped)
Reactive lymphocytes
*larger than normal
variant of reactive lymphocyte which is also called
*with basophilic, vacuolated, foamy appearance of cytoplasm
Plasmacytoid Lymphocyte, Basophilic Lymphocyte, and the Turk’s irritation cell
*in transition to plasma cells; functionally immunocompetent
origin of type I reactive lymphocyte
B-cell
variant of reactive lymphocyte with infectious mononucleosis cells which is seen in EBV or CMV and others reactive conditions
type II
*Fried egg or flared skirt appearance
® Cytoplasm: abundant and indented, deep blue with peripheral accentuation, skirting ofcytoplasm around rbcs
Transformed or Reticular Lymphocytes
coarse reticular nuclear pattern
Type III
disorders in absolute lymphocytosis with variant lymphocytes
- Infectious mononucleosis
- Acute Viral Hepatitis
- Cytomegalovirus infections
disorders in Relative lymphocytosis
with variant lymphocytes
- Toxoplasmosis
* Viral-related disorders: MMR, Chickenpox, Viral Pneumonia
[Benign Disorders of Variant Lymphocytes] Immune disorders
- Drug Reactions
- Serum sickness
- Idiopathic thrombocytopenia
- Autoimmune Hemolytic anemia
[Benign Disorders of Variant Lymphocytes] Non-viral infections
- TB • Typhus
- Syphilis • Diphtheria
- Malaria • Brucellosis
- Rickettsia
[Benign Disorders of Variant Lymphocytes]Absolute lymphocytosis
with normal lymphocytes
- Acute infectious lymphocytosis
* Pertussis
[Benign Disorders of Variant Lymphocytes]
Relative lymphocytosis
with normal lymphocytes
• Neutropenia
T or F: Neoplastic disorders of WBCs are derived from a single precursor cell with all the affected cells showing features of deviation from the precursor cell
true
Three types of neoplastic disorders of wbcs
- Myeloproliferative disorders
- Lymphoproliferative disorders
- Immunoproliferative disorders
Malignancies of leukocytes
myeloma
leukemia
malignant proliferation of plasma cells
myeloma
Malignant proliferation of the WBC with the presence of the immature forms in the peripheral circulation
Leukemia
Two classifications of leukemia
• Based on Duration: Acute or Chronic (Adults)
• Based on the Type of Blood Cell Affected:
- Lymphocytic leukemia: lymphoid cells
- Myeloid or myelogenous leukemia: pluripotent myeloid stem cells
Acute leukemia
• With symptoms of depressed bone marrow function: ® Anemia ® Bleeding ® Fatigue ® Infection • Bone pain • Lymphadenopathy • Splenomegaly • Hepatomegaly
lymphocytic leukemia involves
immature lymphocytes and their progenitors that originate in the bone marrow, but infiltrate the spleen, lymph nodes, CNS, and other tissues
MALIGNANT DISORDERS OF VARIANT LYMPHOCYTES
• Acute lymphoblastic (ALL) leukemia (young children)
• Chronic lymphocytic leukemia (CLL) (adults)
• Lymphomas
® Non-Hodgkin’s lymphoma
® Hodgkin’s disease