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blasts - conditions
leukemia
blasts - identification
high nuclear : cytoplasm ratio, fine chromatin
dysplastic neutrophils - conditions
myelodysplastic syndromes (MDS)
rouleaux formation - conditions
multiple myeloma, waldenstrom’s macroglobulinemia, infections, chronic inflammatory diseases
bone marrow aspirate - uses
blast counting, flow cytometry, iron stain, molecular cytogenetics, molecular testing
bone marrow aspirate - areas to examine
around marrow particle (hematopoietic islands) → avoid hemodiluted regions
bone marrow biopsy - obtain
take core sample of solid marrow tissue
bone marrow biopsy - uses
cellularity estimation, fibrosis detection, immunohistochemistry, megakaryocytes assessment
reticulin stain
shows fibrous networks
age-adjusted cellularity formula
expected cellularity = 100 - age ± 10%
age-adjusted cellularity formula - for what
gives expected range of marrow cellularity for a given age
bone marrow biopsy - components to identify
trabecular bone, adipocytes, hematopoietic islands
immunohistochemistry
determine cell phenotypes using labeled antibodies
immunohistochemistry - method
cells are marked using antibodies against surface in intracellular proteins
immunohistochemistry - brown staining
positive cells of interest
CD61 - identifies
megakaryocytes
CD34 - identifies
hematopoietic stem cells, blasts
CD71 - identifies
erythroid precursors
MPO - identifies
myeloid cells
imaging studies - purpose
detect occult lymphadenopathy
imaging studies - assess what
bone metastasis, osteolytic lesions, abnormal bone marrow signals
complete blood count (CBC) - includes what
hemaglobin, hematocrit, MCV, MCH, MCHC, white blood cell differential, platelet count
serum protein electrophoresis (SPEP)
separate serum proteins by charge, size and shape
serum protein electrophoresis (SPEP) - used when
total protein is elevated, suspicion of plasma cell disorders
serum protein electrophoresis (SPEP) - what diagnosis
multiple myeloma, waldenstrom macroglobulinemia, amyloidosis
immunofixation electrophoresis - electrophoresis phase
separate proteins
immunofixation electrophoresis - fixation phase
use specific antibodies to identify immunoglobulins
immunofixation electrophoresis compared to serum protein electrophoresis
more specific for identifying monoclonal proteins
immunofixation electrophoresis - what diagnosis
multiple myeloma, waldenstrom macroglobulinemia, systemic amyloidosis
ADAMTS13 enzyme assay
measures activity of ADAMTS13
ADAMTS13
cleaves large vWF multimers
decrease ADAMTS13 - pathophysio
uncleaved vWF multimers → excessive platelet aggregation → microthrombi → organ ischemia
ADAMTS13 deficiency - condition
thrombotic thrombocytopenic purpura (TTP)
flow cytometry
evaluates multiple cell surface markers using fluorochrome-labeled antibodies
flow cytometry - diagnose what
leukemia, lymphoma, B or T cell clonality
B lymphocyte panel
specific flow cytometry panel to study B cell populations
B lymphocyte panel - purpose
distinguish monoclonal (malignant) from polyclonal (reactive) expansions & look for kappa and lambda light chain restrictions
conventional karyotyping
analyze chromosome structure and number
conventional karyotyping - purpose
identify translocations, deletions, aneuploidy
fluorescence in situ hybridization
use fluorescent probes to detect specific chromosomal rearrangements
molecular genetic testing - used when
specific mutations are suspected
next generation sequencing - analyze what
entire genomes, targeted gene panels, RNA transcripts
anemia
low RBC
leukopenia
low WBC
thrombocytopenia
low platelet
bicytopenia
decrease in 2 cell lines
pancytopenia
decrease in all 3 cell lines
cytopenia - grouped causes
inherited & neoplastic
cytopenia - inherited causes
fanconi anemia, shwachman-diamond syndrome, familial aplastic anemia, dyskeratosis congenita, evans syndrome
fanconi anemia - genetic
autosomal recessive
fanconi anemia - gene mutation
FANCA
fanconi anemia - effect
defective double-stranded DNA repair
shwachman-diamond syndrome - genetic
autosomal recessive
shwachman-diamond syndrome - gene mutation
SBDS on chromosome 7
shwachman-diamond syndrome - triad
exocrine pancreatic insufficiency, skeletal abnormalities, bone marrow failure
familial aplastic anemia - effect
isolated features of aplastic anemia → bone marrow failure
dyskeratosis congenita - genetics
x-linked
dyskeratosis congenita - gene mutation
telomere repair genes
dyskeratosis congenita - triad
abnormal nails, reticular skin pigmentation, oral leukoplakia
evans syndrome - what is it
autoimmune condition with 2 or more cytopenias
evans syndrome - common conditions
autoimmune hemolytic anemia (AIHA) & immune thrombocytopenia (ITP)
evans syndrome - classes
primary (idiopathic) & secondary
cytopenia - neoplastic causes
myelodysplastic syndrome (MDS), lymphomas, multiple myeloma, metastatic disease, leukemia
myelodysplastic syndrome (MDS)
clonal hematopoietic disorder leading to ineffective hematopoiesis
zinc-induced copper deficiency
mimics myelodysplastic syndrome morphologically
zinc-induced copper deficiency - blood smear
pseudo-pelger-huet anomaly (bilobed nucleus) & vacuolated erythroid precursors
lymphomas - what is it
malignancy of lymphocytes, may involved bone marrow
lymphomas - clinical features
lymphodenopathy, splenomegaly
hodgkin lymphoma - origin
B cell
hodgkin lymphoma - histo examination
reed-sternberg (RS) cells
hodgkin lymphoma - associated with
EBV
non-hodgkin lymphoma - origin
B or T cells
multiple myeloma - what is it
malignancy of plasma cells producing monoclonal immunoglobulins
multiple myeloma - symptoms
CRAB → calcium elevation (hypercalcemia), renal failure, bone lesions (back pain), anemia, punched out lesions
acute leukemia - what is it
rapid proliferation of blasts (immature cells)
acute leukemia - criteria
>= 20% blasts in blood or bone marrow
acute leukemia - types
acute myeloid leukemia (AML) & acute lymphoid leukemia (ALL)
acute leukemia - cytogenic markers
t(8;21), t(15;17), inv(16)
acute leukemia - can be diagnosed when
cytogenic markers preset even if blast < 20%
chronic leukemia - what is it
proliferation of mature or maturing cells
chronic leukemia - types
chronic myeloid leukemia (CML) & chronic lymphoid leukemia (CLL)
leukemia - diagnosis with what
peripheral smear, bone marrow biopsy, flow cytometry
leukocytosis
increase in WBC
erythrocytosis
increase in RBC
thrombocytosis
increase platelets
panmyelosis
increased all 3 leanages
cythemia
malignant (clonal) increase in blood cell types due to myeloproliferative neoplasm (MPNs)
inappropriate increase of erythropoietin
renal cell carcinoma (RCC)
EPO binds to receptors on erythroid progenitor cells leads to…
JAK2 activation
JAK2 activation leads to…
intracellular signalling → transcription of genes → erythroid progenitor survival, proliferation, differentiation into RBCs
polycythemia vera (PV) - mutation
JAK2 V617F
polycythemia vera (PV) - characterized by
low/normal EPO despite erythrocytosis, increased RBC, WBC platelets, hypercellular bone marrow
polycythemia vera (PV) - clinical features
facial plethora (red face), erythomelalgia (burning pain in hands feet)
leukocytosis - causes
physiologic / reactive (infection inflammation) OR clonal disorders (leukemia, myeloproliferative neoplasms)
leukemoid reaction - what is it
benign reactive increase in WBC in response to severe infection or stress
leukemoid reaction - blood smear
mature neutrophils, toxic granulation in neutrophils, minimal left shift (no myeloblast or promyelocytes)
leukemoid reaction - cause
infection / inflammation
leukemoid reaction - blood smear
neutrophils, band cells, metamyelocytes, myelocytes, toxic granules, NO BLAST
leukemoid reaction - differential
left shift → neutrophil predominance
chronic myeloid leukemia (CML) - what is it
clonal myeloproliferative neoplasm by uncontrolled proliferation of mature and maturing myeloid cells