Must Know WBC Disorders Flashcards
Gamma chain or adenosine deaminase (ADA) deficiency deficiency caused by mutations in the IL2RG gene
Severe Combined Immune Deficiency
There is a risk of bleeding due to thrombocytopenia and small abnormal platelets
Wiskott-Aldrich Syndrome
Variable degrees of immunodeficiency because of the absence or decreased size of the thymus and low numbers of T lymphocytes.
22q11 Syndromes
Reductions in all serum immunoglobulin isotypes and profoundly decreased or absent B cells.
Bruton Tyrosine Kinase Deficiency
Exhibit abnormally large lysosomes, which contain fused dysfunctional granules. S/S includes partial albinism
and severe recurrent life-threatening bacterial infections
Chédiak-Higashi Syndrome
Inability of neutrophils and monocytes to move from circulation to the site of inflammation (called extravasation).
Leukocyte Adhesion Disorders (Defects of Motility)
Decreased ability of neutrophils to undergo a respiratory burst after phagocytosis of foreign organisms.
Chronic granulomatous disease (CGD)
Decreased nuclear segmentation/hypo segmentation with “pince-nez” nuclei caused by a mutation in the lamin B receptor
Pelger-Huët Anomaly
Hyper segmented neutrophils
Megaloblastic anemia (Normal neutrophils contain three to five lobes that are separated by filaments)
Characterized by granulocytes (monocytes and lymphocytes less often) with large, darkly staining metachromatic cytoplasmic granules, also found in the mucopolysaccharidoses (MPSs)
Alder-Reilly Anomaly
Variable thrombocytopenia, giant platelets, and often thrombocytopenia caused by mutations in nonmuscle myosin heavy-chain IIA
May-Hegglin Anomaly
Defect or deficiency in the catabolic enzyme b-glucocerebrosidase causing accumulation of sphingolipid glucocerebroside in macrophages
Gaucher Disease
Gaucher cells- wrinkled appearance (sometimes described as onion skin-like)
Deficiency of sphingomyelinase and a subsequent buildup of the substrate sphingomyelin
Niemann-Pick Disease
Reactive neutrophilic leukocytosis greater than 50 x 10⁹/L with a shift to the left.
Leukemoid reaction
Dark, blue-black granules in the cytoplasm of neutrophils, usually in segmented and band form
Toxic Granulation
- One helpful defining characteristic of toxic granulation is that in most cases, not all neutrophils are equally affected
- Associated with inflammation & infection
Cytoplasmic inclusions consisting of remnants of ribosomal ribonucleic acid (RNA) arranged in parallel rows and are typically found in band and segmented neutrophils
Döhle bodies
(* Howell- Jolly bodies- DNA remnants in RBCs)
WBC malignant disorder which usually originate in the bone marrow but can invade other tissues including the lymphatic system.
Leukemia
WBC malignant disorder which usually originate in the lymphoid tissues but can invade other tissues including the bone marrow.
Lymphoma
Malignancy involving plasma cells
Myeloma
_ % blasts in bone marrow or blood are typically found in Acute leukemias
> 20 %
Myeloperoxidase and Sudan Black B (+) is present in what type of leukemia?
AML or myelogenous leukemias
Periodic acid- Schiff (+) is present in what type of leukemia?
Erythroleukemia, ALL or lymphocytic leukemias
Increased TdT activity level is present in what type of leukemia?
ALL (Acute Lymphoid Leukemia)
Philadelphia chromosome (translocation of chromosome 9 & 22 causing fusion of BCR- ABL gene) is present in what type of leukemia?
CML (Chronic myelogenous leukemia)
Difference between CML and leukemoid reaction in terms of LAP score?
Low- CML
High- Leukemoid reaction
Reider cells and smudge cells are found in what type of leukemia?
CLL (Chronic lymphoid Leukemia)
Abnormal plasma cell with red-staining cytoplasm
Flame cell
WBC malignant disorder not inhibited with tartaric acid
Hairy cell leukemia
Chromosomal analysis showing ______ (hyperdiploidy or hypodiploidy) renders a good prognosis in ALL.
Hyperdiploidy (excess numbers of chromosomes; as many as 51-67 chromosomes compared to the normal 46 chromosomes)
(+) Philadelphia chromosome in ALL indicated bad or good prognosis?
BAD prognosis
(+) Philadelphia chromosome in CML indicated bad or good prognosis?
GOOD prognosis
JAK2 V617F mutation is found in?
Primary polycythemia vera
group of genetic immunodeficiencies affecting both cellular and humoral immunity.
Severe combined immune deficiency (SCID)
- Circulating T and natural killer (NK) lymphocytes are nearly absent.
- B cells are adequate in number but are dysfunctional
Severe combined immune deficiency (SCID)
represents 10% to 20% of SCID cases and is caused by one of many mutations in the ADA gene located at chromosome 20q13.12.
Autosomal recessive adenosine deaminase ADA deficiency
results in an intra and extracellular accumulation of adenosine, which is lymphotoxic, leading to profound decreases in T, B, and NK cells.
ADA deficiency
is classified as a combined immunodeficiency.
Wiskott-Aldrich Syndrome
It is a rare X-linked disease caused by one of more than 400 mutations in the WAS gene, which results in decreased levels of WASp protein
Wiskott-Aldrich Syndrome
T cells are decreased; B cells, T cells and NK cells, neutrophils and monocytes are dysfunctional which leads to bacterial, viral and fungal infections.
Wiskott-Aldrich Syndrome
Classified as an antibody deficiency,
Bruton Tyrosine Kinase Deficiency (X-linked agammaglobulinemia)
primary immunodeficiency disease characterized by reductions in all serum immunoglobulin isotypes and profoundly decreased or absent B cells.
Bruton Tyrosine Kinase Deficiency (X-linked agammaglobulinemia)
is a rare autosomal recessive disease of immune dysregulation
Chédiak-Higashi Syndrome
associated with a mutation in the CHS1 LYST gene on chromosome 1q42 that encodes for a protein that regulates the morphology and function of lysosome-related organelles.
Chédiak-Higashi Syndrome
giant lysosomal granules in granulocytes, monocytes, and lymphocytes
Chédiak-Higashi Syndrome
are cytoplasmic inclusions that resemble the fused lysosomal granules in Chédiak-Higashi syndrome
Pseudo-Chédiak-Higashi granules
rare group of genetic diseases characterized by low neutrophil count, increased risk of infection, organ dysfunction, and a high rate of leukemic transformation
Congenital Defects of Phagocytes (congenital neutropenias (CNs)
rare autosomal recessive inherited conditions resulting in the inability of neutrophils and monocytes to move from circulation to outside-in signaling.
Leukocyte Adhesion Disorders (Defects of Motility)
Lymphadenopathy, splenomegaly, and neutrophilia are common findings.
Leukocyte Adhesion Disorders (Defects of Motility)
molecular defects in SLC35C1, which codes for a fucose transporter that moves fucose from the endoplasmic reticulum to the Golgi region.
LAD II
caused by mutations in Kindlin-3 ( Kindlin-3 protein along with talin are required for activation of b integrin and leukocyte rolling.)
LAD III
is a defect in leukocyte motility.
Shwachman-Diamond syndrome (SDS)
rare autosomal recessive disease caused by mutations in the SBDS gene located at 7q11.22.
Shwachman-Diamond syndrome (SDS)
affects the SBDS protein product which has an important role in ribosomal maturation, cell proliferation and bone marrow microenvironment.
Shwachman-Diamond syndrome (SDS)
rare condition caused by the decreased ability of neutrophils to undergo a respiratory burst after phagocytosis of foreign organisms.
Defects of Respiratory Burst (Chronic granulomatous disease (CGD)
caused by mutations in genes responsible for proteins that make up the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.
Defects of Respiratory Burst (Chronic granulomatous disease (CGD)
patients experience life-threatening catalase-positive bacterial and fungal infections.
Defects of Respiratory Burst (Chronic granulomatous disease (CGD)
is classified as a defect in intrinsic and innate immunity. results from mutations in the CXCR4 gene located at 2q22.
WHIM Syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis syndrome)
neutropenia, lymphopenia, monocytopenia, and hypogammaglobulinemia are present.
WHIM Syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis syndrome)
As a result, patients experience recurrent bacterial infections and are highly susceptible to human papillomavirus (HPV) infection, which leads to warts, which can be widespread and resistant to treatment.
WHIM Syndrome (warts, hypogammaglobulinemia, infections, and myelokathexis syndrome)
also known as true or congenital PHA
Pelger-Huët anomaly (PHA)
an autosomal dominant disorder characterized by decreased nuclear segmentation and distinctive coarse chro- matin clumping pattern.
Pelger-Huët anomaly (PHA)
It potentially affects all leukocytes
Pelger-Huët anomaly (PHA)
The disorder is a result of a mutation in the lamin b-receptor gene (The lamin b receptor is an inner nuclear membrane protein that combines b-type lamins and heterochromatin and plays a major role in leukocyte nuclear shape changes that occur during normal maturation.)
Pelger-Huët anomaly (PHA)
- round, ovoid, or peanut shaped
- Bilobed forms— the characteristic spectacle-like (“pince-nez”) morphology with the nuclei attached by a thin filament can also be seen.
Pelger-Huët anomaly (PHA)
associated with severe bacterial infections, HIV, tuberculosis, and mycoplasma pneumonia
Pseudo- or Acquired Pelger-Huët Anomaly
Neutrophils with similar morphology to PHA can be seen in patients with MDS, acute myeloid leukemia, and myeloproliferative neoplasm.
Pseudo- or Acquired Pelger-Huët Anomaly
have more than five lobes and are most often associated with megaloblastic anemia
Neutrophil Hypersegmentation
also be seen in MDS where they represent a form of dysplasia.
Neutrophil Hypersegmentation
a rare inherited disorder characterized by granulocytes (monocytes and lymphocytes less often) with large, darkly staining metachromatic cytoplasmic granules.
Alder-Reilly Anomaly
Initially reported in patients with gargoylism; however, it can be seen in otherwise healthy indi- viduals.
Alder-Reilly Anomaly
The characteristic granulation, called Reilly bodies, is also found in the mucopolysaccharidoses (MPSs). The cytoplasmic granules contain partially digested mucopolysaccharides.
Alder-Reilly Anomaly
Reilly bodies can also be present in monocytes and lymphocytes, whereas toxic granulation occurs only in neutrophils.
Alder-Reilly Anomaly
rare, autosomal dominant disorder characterized by variable thrombocytopenia, giant platelets, and large Döhle body-like inclusions in neutrophils, eosinophils, basophils, and monocytes.
May-Hegglin Anomaly
caused by a mutation in the MYH9 gene on chromosome 22q12-13.
May-Hegglin Anomaly
group of more than 50 inherited enzyme deficiencies resulting from mutations in genes that code for the production of lysosomal enzymes
Lysosomal Storage Diseases
result is flawed degradation of phagocytized material and buildup of undigested substrates within lysosomes. This causes cell dysfunction, cell death, and a range of clinical symptoms. All cells containing lysosomes can be affected..
Lysosomal Storage Diseases
caused by deficient activity of an enzyme necessary for the deg- radation of dermatan sulfate, heparan sulfate, keratan sulfate, and/or chondroitin sulfate.
Mucopolysaccharidoses
The partially degraded material builds up in lysosomes and results in serious physical and cog- nitive problems and shortened survival.
Mucopolysaccharidoses
most common of the lysosomal lipid storage diseases.
Gaucher Disease
autosomal recessive disorder caused by a defect or deficiency in the catabolic enzyme b-glucocerebrosidase (gene located at 1q21-q22), which is necessary for glycolipid metabolism.
Gaucher Disease
an accumulation of fat in cellular lysosomes of vital organs, which impairs their function, leading to a range of clinical findings.
Niemann-Pick Disease
An absolute increase in neutrophils greater than 7.0 3 10 /L in adults or 8.5 3 10 /L in children
Neutrophilia
occur as a result of catecholamine-induced shift in neutrophils from the marginal pool (cells normally adhering to vessel walls) to the circulating pool.
Neutrophilia
often accompanied by a left shift.
Neutrophilia
a reactive neutrophilic leukocytosis greater than 50 3 109/L with a shift to the left.
Leukemoid reaction
caused by acute and chronic infections, metabolic disease, or inflammation or occur as part of an inflammatory response to malignancy.
Leukemoid reaction
refers to the simultaneous presence of immature neutrophils, nucleated red blood cells, and teardrop red blood cells (RBCs).
Leukoerythroblastic reaction
is defined as a decrease in the ANC to less than 2.0 3 109/L in white adults or 1.3 3 109/L in black adults.
Neutropenia
refers to a neutrophil count of less than 0.1 3 109/L. Some causes of neutropenia are
Agranulocytosis
increased rate of removal or destruction of peripheral blood neutrophils
Agranulocytosis
ewer neutrophils re- leased from the bone marrow to the blood because of decreased
production or ineffective hematopoiesis, where neutrophils are present in the bone marrow but not released into circulation be- cause they are defective
Agranulocytosis
Medications are the most common causes of acquired neutropenia. Neutropenia has been associated with almost all classes of drugs and is a result of myeloid suppression or immunologic response.
Drug-induced neutropenia
bone marrow proliferation rate and release into the blood- stream, movement from the blood into extravascular tissues, and cell survival and destruction after eosinophils have moved into the tissues.
Eosinophils
is defined as an absolute eosinophil count greater than 0.4 3 109/L.
Eosinophilia
Major function is degranulation, where substances are released that damage an offending organism (i.e., parasites) or target cell
Eosinophilia
is associated with parasitic infections, especially helminths. It is also associated with allergic reactions, including asthma, rhinitis, urticaria, and atopic dermatitis;
Eosinophilia
defined as an absolute eosinophil count of less than 0.09 3 109/L and can be difficult to detect because the reference interval is low.
Eosinopenia
been reported in autoimmune disorders, steroid therapy, stress, sepsis, and acute inflammatory states.
Eosinopenia
is defined as an absolute basophil count greater than 0.15 3 109/L
Basophils
associated with chronic myeloid leukemia, allergic rhinitis, hypersensitivity to drugs or food, chronic infections, hypothyroidism, chronic inflammatory conditions, radiation therapy, and bee stings.
Basophils
defined as an absolute monocyte count greater than 1.0 3 109/L in adults and greater than 3.5 3 109/L in neonates.
Monocytosis
associated with numerous conditions because of their role in acute and chronic inflammation and infections, immunologic conditions, hypersensitivity reactions, and tissue repair.
Monocytosis
often the first sign of recovery after myelosuppression.
Monocytosis
defined as an absolute monocyte count of less than 0.2 3 109/L, is very rare in conditions that do not also involve cytopenias of other lineages, such as aplastic ane- mia or chemotherapy-induced cytopenias.
Monocytopenia
has been found in patients receiving steroid therapy75 or he- modialysis and in sepsis.
Monocytopenia
Identification of lymphocytosis varies with the age of the individual. Children between 2 weeks and 8 to 10 years of age have higher absolute lymphocyte counts than adults. In adults, lymphocytes represent 20% to 40% of circulating leukocytes.
Lymphocytes
- in children is defined as an absolute lymphocyte count greater than 10.0 3 109/L,
- whereas in adults it is defined as a count greater than 5.0 3 109/L.
Lymphocytosis
- in children is defined as an absolute lymphocyte count less than 2.0 3 109/L,
- whereas in adults it is defined as a count less than 1.0 3 109/L.
Lymphocytopenia
