T10 WBC disorders

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145 Terms

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blasts - conditions

leukemia

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blasts - identification

high nuclear : cytoplasm ratio, fine chromatin

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dysplastic neutrophils - conditions

myelodysplastic syndromes (MDS)

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rouleaux formation - conditions

multiple myeloma, waldenstrom’s macroglobulinemia, infections, chronic inflammatory diseases

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bone marrow aspirate - uses

blast counting, flow cytometry, iron stain, molecular cytogenetics, molecular testing

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bone marrow aspirate - areas to examine

around marrow particle (hematopoietic islands) → avoid hemodiluted regions

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bone marrow biopsy - obtain

take core sample of solid marrow tissue

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bone marrow biopsy - uses

cellularity estimation, fibrosis detection, immunohistochemistry, megakaryocytes assessment

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reticulin stain

shows fibrous networks

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age-adjusted cellularity formula

expected cellularity = 100 - age ± 10%

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age-adjusted cellularity formula - for what

gives expected range of marrow cellularity for a given age

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bone marrow biopsy - components to identify

trabecular bone, adipocytes, hematopoietic islands

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immunohistochemistry

determine cell phenotypes using labeled antibodies

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immunohistochemistry - method

cells are marked using antibodies against surface in intracellular proteins

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immunohistochemistry - brown staining

positive cells of interest

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CD61 - identifies

megakaryocytes

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CD34 - identifies

hematopoietic stem cells, blasts

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CD71 - identifies

erythroid precursors

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MPO - identifies

myeloid cells

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imaging studies - purpose

detect occult lymphadenopathy

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imaging studies - assess what

bone metastasis, osteolytic lesions, abnormal bone marrow signals

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complete blood count (CBC) - includes what

hemaglobin, hematocrit, MCV, MCH, MCHC, white blood cell differential, platelet count

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serum protein electrophoresis (SPEP)

separate serum proteins by charge, size and shape

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serum protein electrophoresis (SPEP) - used when

total protein is elevated, suspicion of plasma cell disorders

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serum protein electrophoresis (SPEP) - what diagnosis

multiple myeloma, waldenstrom macroglobulinemia, amyloidosis

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immunofixation electrophoresis - electrophoresis phase

separate proteins

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immunofixation electrophoresis - fixation phase

use specific antibodies to identify immunoglobulins

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immunofixation electrophoresis compared to serum protein electrophoresis

more specific for identifying monoclonal proteins

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immunofixation electrophoresis - what diagnosis

multiple myeloma, waldenstrom macroglobulinemia, systemic amyloidosis

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ADAMTS13 enzyme assay

measures activity of ADAMTS13

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ADAMTS13

cleaves large vWF multimers

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decrease ADAMTS13 - pathophysio

uncleaved vWF multimers → excessive platelet aggregation → microthrombi → organ ischemia

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ADAMTS13 deficiency - condition

thrombotic thrombocytopenic purpura (TTP)

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flow cytometry

evaluates multiple cell surface markers using fluorochrome-labeled antibodies

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flow cytometry - diagnose what

leukemia, lymphoma, B or T cell clonality

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B lymphocyte panel

specific flow cytometry panel to study B cell populations

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B lymphocyte panel - purpose

distinguish monoclonal (malignant) from polyclonal (reactive) expansions & look for kappa and lambda light chain restrictions

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conventional karyotyping

analyze chromosome structure and number

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conventional karyotyping - purpose

identify translocations, deletions, aneuploidy

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fluorescence in situ hybridization

use fluorescent probes to detect specific chromosomal rearrangements

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molecular genetic testing - used when

specific mutations are suspected

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next generation sequencing - analyze what

entire genomes, targeted gene panels, RNA transcripts

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anemia

low RBC

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leukopenia

low WBC

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thrombocytopenia

low platelet

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bicytopenia

decrease in 2 cell lines

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pancytopenia

decrease in all 3 cell lines

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cytopenia - grouped causes

inherited & neoplastic

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cytopenia - inherited causes

fanconi anemia, shwachman-diamond syndrome, familial aplastic anemia, dyskeratosis congenita, evans syndrome

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fanconi anemia - genetic

autosomal recessive

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fanconi anemia - gene mutation

FANCA

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fanconi anemia - effect

defective double-stranded DNA repair

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shwachman-diamond syndrome - genetic

autosomal recessive

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shwachman-diamond syndrome - gene mutation

SBDS on chromosome 7

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shwachman-diamond syndrome - triad

exocrine pancreatic insufficiency, skeletal abnormalities, bone marrow failure

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familial aplastic anemia - effect

isolated features of aplastic anemia → bone marrow failure

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dyskeratosis congenita - genetics

x-linked

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dyskeratosis congenita - gene mutation

telomere repair genes

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dyskeratosis congenita - triad

abnormal nails, reticular skin pigmentation, oral leukoplakia

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evans syndrome - what is it

autoimmune condition with 2 or more cytopenias

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evans syndrome - common conditions

autoimmune hemolytic anemia (AIHA) & immune thrombocytopenia (ITP)

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evans syndrome - classes

primary (idiopathic) & secondary

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cytopenia - neoplastic causes

myelodysplastic syndrome (MDS), lymphomas, multiple myeloma, metastatic disease, leukemia

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myelodysplastic syndrome (MDS)

clonal hematopoietic disorder leading to ineffective hematopoiesis

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zinc-induced copper deficiency

mimics myelodysplastic syndrome morphologically

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zinc-induced copper deficiency - blood smear

pseudo-pelger-huet anomaly (bilobed nucleus) & vacuolated erythroid precursors

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lymphomas - what is it

malignancy of lymphocytes, may involved bone marrow

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lymphomas - clinical features

lymphodenopathy, splenomegaly

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hodgkin lymphoma - origin

B cell

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hodgkin lymphoma - histo examination

reed-sternberg (RS) cells

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hodgkin lymphoma - associated with

EBV

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non-hodgkin lymphoma - origin

B or T cells

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multiple myeloma - what is it

malignancy of plasma cells producing monoclonal immunoglobulins

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multiple myeloma - symptoms

CRAB → calcium elevation (hypercalcemia), renal failure, bone lesions (back pain), anemia, punched out lesions

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acute leukemia - what is it

rapid proliferation of blasts (immature cells)

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acute leukemia - criteria

>= 20% blasts in blood or bone marrow

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acute leukemia - types

acute myeloid leukemia (AML) & acute lymphoid leukemia (ALL)

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acute leukemia - cytogenic markers

t(8;21), t(15;17), inv(16)

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acute leukemia - can be diagnosed when

cytogenic markers preset even if blast < 20%

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chronic leukemia - what is it

proliferation of mature or maturing cells

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chronic leukemia - types

chronic myeloid leukemia (CML) & chronic lymphoid leukemia (CLL)

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leukemia - diagnosis with what

peripheral smear, bone marrow biopsy, flow cytometry

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leukocytosis

increase in WBC

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erythrocytosis

increase in RBC

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thrombocytosis

increase platelets

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panmyelosis

increased all 3 leanages

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cythemia

malignant (clonal) increase in blood cell types due to myeloproliferative neoplasm (MPNs)

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inappropriate increase of erythropoietin

renal cell carcinoma (RCC)

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EPO binds to receptors on erythroid progenitor cells leads to…

JAK2 activation

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JAK2 activation leads to…

intracellular signalling → transcription of genes → erythroid progenitor survival, proliferation, differentiation into RBCs

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polycythemia vera (PV) - mutation

JAK2 V617F

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polycythemia vera (PV) - characterized by

low/normal EPO despite erythrocytosis, increased RBC, WBC platelets, hypercellular bone marrow

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polycythemia vera (PV) - clinical features

facial plethora (red face), erythomelalgia (burning pain in hands feet)

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leukocytosis - causes

physiologic / reactive (infection inflammation) OR clonal disorders (leukemia, myeloproliferative neoplasms)

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leukemoid reaction - what is it

benign reactive increase in WBC in response to severe infection or stress

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leukemoid reaction - blood smear

mature neutrophils, toxic granulation in neutrophils, minimal left shift (no myeloblast or promyelocytes)

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leukemoid reaction - cause

infection / inflammation

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leukemoid reaction - blood smear

neutrophils, band cells, metamyelocytes, myelocytes, toxic granules, NO BLAST

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leukemoid reaction - differential

left shift → neutrophil predominance

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chronic myeloid leukemia (CML) - what is it

clonal myeloproliferative neoplasm by uncontrolled proliferation of mature and maturing myeloid cells