Hematology Flashcards
Burkitt Lymphoma
genetic abnormality
main features - endemic form vs. non
biopsy
t(8;14) puts c-myc with Ig promoter
jaw tumor + LAP in Africans due to EBV
(non-endemic can be abdominal tumor w/ rapid doubling + spontaneous tumor lysis)
biopsy shows “starry sky” of macrophages + apoptotic bodies among many lymphocytes; malig B-lymphos have vacuolated cytoplasm
Follicular Lymphoma
translocation
biopsy
presentation
t(14;18) puts Ig promoter with BCL-2
composed of small-cleaved “centrocytes” with larger uncleaved “centroblasts”; low mag biopsy is highly packed B-cell follicles without normal nodal architecture
pts are middle-age with painless, fluctuating LAP or abd. pain with abdominal masses
Eosinophilic (M4Eo subtype) AML
inv(16)
CML
translocation
special histo
chronic stable presentation
t(9;22) BCR-ABL fusion protein
NO AUER RODS bc cells are more mature!
many different precursor cell types (not just blasts)
present with non-specific symptoms in chronic stable phase
APML
translocation?
presentation (2)?
tx?
t(15;17) puts RARA with PML; see Auer rods in promyelocytes
presents with DIC +/- fever via low WBCs
tx with ATRA (induces PML/RARA degradation + stimulates maturation)
mantle cell lymphoma
translocation
t(11;14) puts cyclin D1 near Ig heavy chain; cyclin D1 promotes G1 to S transition
Diffuse Large B-cell lymphoma
epidemiology
presentation
1 NHL
rapid growing nodal (neck, abd, mediastinum) or extranodal symptomatic mass; commonly in tonsils or GI tract
systemic B symptoms common
Acute Lymphoblastic Leukemia
epidemiology
5 s/s
1 kid leukemia; composed of pre-B (CD19/10) or pre-Ts (CD1/2/5)
LAP, HSmegaly, fever, bleeding + bone pain
Hairy Cell Leukemia
in whom? 2 s/s and one absent sx
histo + special staining positivity
splenomegaly + pancytopenia in older men; no LAP!
hairy cells and TRAP+
Mycosis fungoides
cell type? histo feature?
derma description?
cutaneous T-cell lymphoma
CD4+ cells infiltrate dermis/epidermis > Pautrier microabscesses
plaques on trunk/butt look like eczema/psoriasis; may see generalized erythema / erythroderma
LAP score
what is it? what does it indicate? other ways (1 main, 3 minor) to differentiate the 2 conditions LAP score differentiates
Leukocyte Alkaline Phosphatase
normal or increased in LEUKEMOID REACTION
decreased in CML
Dohle bodies - basophilic PERIPHERAL granules in neutrophils of leukemoid reaction (rER ribosomes), or pt with burns or myelodysplasia
Other signs of leukemoid reaction:
Increased bands (left shift)
Toxic granulation - cytoplasmic granules in neutros
Cytoplasmic vacuoles
Leukemoid Reaction
what is it? differential?
benign leukocytosis (>50,000) due to severe infection, hemorrhage, solid tumor or acute hemolysis
marrow is hypercellular to normal; see INCREASED BANDS and early mature neutrophil precursors (myelocytes, etc.)
high LAP score
Dohle bodies - peripheral basophilic rER in neutros
Cytoplasmic vacuoles - in neutros
Toxic granulation - in neutros
Hereditary Spherocytosis
inheritance + mutations?
smear?
manifestations (3)?
AD mutation of spectrin/ankyrin
some (not all… unless homozygous I guess) RBCs ~2/3 diameter of normal and lack central pallor
hemolytic anemia, jaundice and splenomegaly
Hereditary Spherocytosis
Labs? (3)
Complications + associations? (2)
Tx?
Labs - high MCHC, negative coombs, increased osmotic fragility
Complications - pigmented gallstones, aplastic crises via parvovirus B19
tx is splenectomy
Inherited Hypercoagulability
2 MCCs
Leiden Factor V - #1 MCC, Va is protein C resistant (no change to aPTT on addition of activated protein C)
Prothrombin mutations
Autoimmune Hypercoagulability
MCC
main serum finding + 3 clinical findings
2 labs
antiphospholipid antibody syndrome
lupus anticoagulant / anticardiolipin Abs plus 1+ of following:
venous thromboembolism
arterial thromboembolism
FREQUENT FETAL LOSS
prolonged aPTT + thrombocytopenia
Lead Poisoning
epidem?
s/s? (6 general, 1 special)
smear?
biochem? 2 enzymes
kids eat paint chips; adults are miners/industrial workers (eg, battery manufacturing) who inhale lead
adults - weakness, abd. pain + constipation
if severe - HA, cognitive sx, peripheral neuropathy
signs - blue “LEAD LINES” at gingivodental junction
smear - basophilic stippling (rRNA) with hypochromic microcytic anemia
d-ALA dehydratase and ferrochelatase inhibition > poor iron incorporation into heme > low Hb
Polycythemia Vera
mutation + result?
labs? (3)
complications, s/s? (1 GI, 1 MSK, 1 vascular, 1 abdominal, 2 derma)
JAK2 mutation (V617F; Val > Phe)
makes stem cells more sensitive to growth factors (EPO, TPO)
labs - increased RBC mass, plasma volume, low EPO (may have high platelets, WBCs)
may have:
thrombosis (viscous blood)
peptic ulcers + pruritus (basophils > histamine)
gout (high turnover)
red (“ruddy”) face
splenomegaly
Main signs for multiple myeloma (4)
others? (3)
elderly patient with... osteolytic lesions hypercalcemia anemia acute kidney injury (CRAB = calcium, renal, anemia, bone)
also…
constipation (via high Ca)
fatigue
recurrent infections
What is “myeloma kidney”?
pathogenesis?
labs? (3)
light chain cast nephropathy - intact Igs can’t pass glomerulus, but light chains (kappa + lambda) can > combine with Tamm-Horsfall proteins to form obstructive casts > tubular rupture
DIPSTICK negative for protein (for albumin only)
spot / 24-hr TURBIDIMETRY positive for protein
urine ELECTROPHORESIS shows light chains
Sometimes dipstick is positive for protein in myeloma patient. Why?
Monoclonal Immunoglobulin Deposition Disease
intact Ig or heavy/light chains deposit in glomerulus and cause NEPHROTIC SYNDROME; then albumin and intact Igs will be found in urine
AML
cell type + features (2)?
epidem?
WHO crit?
myeloblast cells; large nucleus, little cytoplasm, AUER RODS with PEROXIDASE positivity
mostly >65 pts with signs of pancytopenia
WHO - at least 20% blasts in marrow (peripheral WBCs median 15,000 at dx)
large CD19 and CD10+ cells in periphery in kid
dx?
precursor B-ALL
large CD1, CD2, and CD5+ cells in periphery in kid
dx?
precursor T-ALL
variable CD1a expression
CDs 2, 3, 4, 5, 7 and 8 are expressed (T cell markers)
Mature B Cell Leukemia
other names?
cells?
CDs?
chronic lymphocytic leukemia -or- small lymphocytic leukemia
small, round, monomorphic B cells in blood, marrow + nodes
CD19 and CD5 (a T cell marker!)
Primary Myelofibrosis
primary pathogenesis?
result?
clonal MEGAKARYOCYTES secrete TGF-BETA > stimulates fibroblasts in marrow to produce collagen > marrow fibrosis
HSCs migrate to liver + spleen > EXTRAMEDULLARY HEMATOPOIESIS
Primary Myelofibrosis
manifestations (5)?
think systemic, GI, hematologic and biopsy
- severe fatigue
- hepatomegaly with MASSIVE SPLENOMEGALY (can compress stomach and cause GI sx)
- at least 1 CYTOPENIA
- “Teardrop cells” aka dacrocytes (rbc damage in spleen or fibrotic marrow)
- DRY TAP on marrow aspiration; must biopsy marrow
Primary Myelofibrosis
risks?
histo?
risks - chemical exposure (toluene, benzene)
histo - hypocellular marrow and significant fibrosis with atypical megakaryocytes (biopsy only… tap usually dry)
Smear findings in beta thalassemia
2 main things; 5 extra
- hypochromic microcytic anemia (MCV <80)
- increased central pallor
“anisopoikilocytosis” varied shape and size
target cells, teardrop cells, nucleated precursors
basophilic stippling
what happens with alpha chains in beta thalassemia?
consequences (2)?
unpaired alpha chains precipitate in RBCs
damage membrane > precursor death > ineffective erythropoiesis
lysis of circulating cells > extravascular hemolysis
Pathogenesis of bone lesions in MM
IL-1 (activates osteoclasts) and IL-6 from neoplastic cells leads to resorption and OSTEOPENIA
(pain, fractures and “punched out” lesions on xray
hypercalcemia > fatigue, confusion, constipation)
Hyperimmunoglobulinemia in MM
causes what in blood (2)?
labs (2)?
rouleaux on peripheral smear
increased ESR
M protein in serum
M spike on electrophoresis
accumulation of light chains throughout body in MM
name?
microscopy?
organs affected (4)?
AL amyloidosis
eosinophilic extracellular deposits on light micro
CONGO stain > “apple green” birefringence
mainly KIDNEY, also heart, tongue and nervous system
Reed-Sternberg cells are derived from what?
germinal center B cells
Thrombotic Thrombocytopenic Purpura
pathophys
low ADAMTS13 (either acquired auto-Ab or hereditary)
uncleaved vWF > platelet trapping > microvascular thrombosis and microangiopathic hemolytic anemia
Thrombotic Thrombocytopenic Purpura
clinical features
microangiopathic HEMOLYSIS with SCHISTOCYTES
THROMBOCYTOPENIA with normal PT/aPTT
sometimes:
renal failure
neurologic sx (ex: lacunar infarct with focal pure sensory loss)
FEVER
TTP
treatment (3)
plasma exchange
steroids
rituximab
Idiopathic Aplastic Anemia
2 general pathomechanisms
3 classes of causes with examples
either direct TOXIC insult or T-CELL RESPONSE against precursors
- Toxins - gasoline, tobacco smoke
- Drugs - CHEMo, CARbamazepine
- Viruses - hepatitis, EBV
(gas goes in CARS; tobacco smoke contains CHEMicals)
Inherited cause of aplastic anemia?
musculoskeletal changes? (2)
increases risk of? (2)
Fanconi anemia
short stature + no thumbs
risk of malignancy (MDS and AML)
Sideroblastic Anemia
MCCs
(5 things w/ examples)
alcohol abuse copper or B6 deficiency meds - isoniazid, chloramphenicol, linezolid myelodysplastic syndrome X-linked form - d-ALA synthase defic.
mechanism of isoniazid or B6 defic. sideroblastic anemia
INH inhibits PYRIDOXINE PHOSPHOKINASE, normally converts pyridoxine to to pyr-5-phosphate
pyr-5-P is a d-ALA SYNTHASE cofactor in heme synth
sideroblastic anemia
peripheral smear (2) stain
- microcytic hypochromic anemia
- ringed sideroblasts - iron granules accumulate around nucleus
Prussian blue stain
reticulocyte appearance on peripheral smear
slightly larger and BLUER with WRIGHT-GIEMSA than RBC
blue due to retention of RIBOSOMAL RNA in a reticular network in the cytoplasm
Howell Jolly bodies
what are they?
DNA remnants in reticulocytes
seen in splenectomy or low spleen function (normally removed by spleen)
What are Pappenheimer bodies?
ferritin aggregates in RBCs / reticulocytes
seen in sideroblastic anemia
Hematological signs of CML
general and more specific, 4 points overall
- elevated WBCs with increased precursor forms
- decreased LAP score
- “myelocytic bulge” - predominance of myelocytes as opposed to more mature metamyelocytes
- absolute BASOPHILIA and/or EOSINOPHILIA
Pure Red Cell Aplasia
what causes it? 2 causes (1 has 2 disease examples)
what 2 tests can help determine cause
inhibition of erythrocytic precursors by IgG AUTOANTIBODIES or CYTOTOXIC T CELLS
- immune dysfunction - THYMOMA (IgG auto-Abs; thymoma removal sometimes cures aplasia) and LYMPHOCYTIC LEUKEMIA (self-reactive CD8+)
- PARVO B19 can also cause it
all prca patients should have CHEST CT for thymoma and ANTI-B19 IgM serum test
Hodgkin lymphoma
epidemiology (2 groups)?
main presenting sx?
BIMODAL AGE dist (peak in 20s and 60s)
- NONTENDER lymphadenopathy (or incidental LAP on routine chest cxr)
- B symptoms - fever, night sweat, weight loss
Hodgkin lymphoma
dx (smear? cbc? definitive?)
peripheral smear + cbc usually normal
NODE BIOPSY is definitive dx - REED-STERNBERG CELLS with lymphos, histiocytes and eosinophils
Differential: vW disease vs. hemophilia vs. ITP
vWD - skin + mucosa bleeding (epistaxis, heavy period, gingival, GI) since childhood; labs show only increased bleeding time + aPTT (factor VIII)
hemophilia - DEEPER bleeding into joints/muscles, GI + urinary tract; labs show high aPTT (intrinsic path)
ITP - EPISODIC bleeding that is MUCOCUTANEOUS with purpura, petechia + epistaxis; labs show low PLTs and high bleeding time
Hemophilia A or B
lab characteristics?
prolonged aPTT only
(normal PT, BT and PLTs)
deficiency factor VIII or IX (intrinsic path)
vW disease
lab characteristics?
prolonged aPTT and bleeding time
(normal PT and PLTs; aPTT can be normal)
aggregation studies can be normal
platelet can’t bind collagen properly due to impaired bridging via vWF (Gp1b), plus vWF doesnt protect factor VIII
DIC
lab characteristics
prolonged BT, PT, aPTT and low PLTs
consumptive coagulopathy uses up all factors + platelets
How does chronic kidney disease affect hemostasis?
labs?
Uremia-induced platelet dysfunction (toxins impair platelet agg + adhesion)
Prolonged BT
normal PT, aPTT and PLTs
Heparin use
lab characteristics
prolonged aPTT only (low plts only if HIT)
normal PT, BT, and PLTs
only affects thrombin and factor X
Warfarin use
lab characteristics
prolonged PT, minimal prolongation of aPTT
normal BT and PLTs
affects factors II, VII, IX and X
Factor XIII deficiency
factor XIII function? s/s? labs?
a rare AR disease with DELAYED, recurrent bleeds after trauma, surgery
factor XIII is a transglutaminase that cross-links fibrin polymers to stabilize them; it’s a later process in clot stabilization so effects are delayed
normal bleeding time, PT and aPTT
What are dysfibrinogenemias?
labs?
inherited abnormalities in fibrinogen
can cause excessive bleeding -OR- thrombophilia
alter THROMBIN TIME (TT), as well as PT and aPTT
bleeding time is normal
Idiopathic Thrombocytopenic Purpura:
pathophys, labs, s/s
GpIIb/IIIa auto-Ab
thrombocytopenia (only peripheral smear abnormality); NO fever; PT, aPTT normal
spontaneous bleeding uncommon (unless PLT <10,000)
Thrombotic Thrombocytopenic Purpura:
pathophys, labs, s/s
ADAMTS12 auto-Ab causes activation of platelets by long vWF polymers
don’t bleed usually; fibrinogen, PT and aPTT normal
TTP-HUS
pentad
- fever
- neurological sx - progressive lethargy
- renal failure
- anemia
- thrombocytopenia
in setting of antecedent GI illness
Beta Thalassemia Minor
what kind of anemia? what kind of cells on smear? what kind of hemoglobin is high?
microcytic hypochromic
increased HbA2 (alpha2delta2) and sometimes high HbF
poikilocytes including SPHEROCYTES and TARGET CELLS
but pt is ASYMPTOMATIC bc this is “minor” variant
Beta Thalassemia
generally what do the mutations affect?
mutations affecting transcription, processing and translation of mRNA for beta-globin
usually aberrant splicing or premature chain termination during translation
sometimes pt mutation prevent RNA polymerase from binding promoter
How does beta thalassemia result in hemolysis?
insoluble ALPHA CHAIN TETRAMERS precipitate in RBCs and cause membrane instability
Most common cause of extramedullary hematopoiesis?
severe chronic hemolytic anemia
as in beta thalassemia, etc.
what non-hematological complication is common in patients with extramedullary hematopoiesis?
Skeletal abnormalities (expanding mass of progenitor cells in marrow thins cortex + impairs growth)
- Pathologic fractures
- Maxillary overgrowth
- Frontal bossing
JAK2
what is it and what does it do?
mutations cause what? (3)
a CYTOPLASMIC (non-receptor) TYR KINASE
activates the STAT pathway (“signal transducers and activators of transcription”)
Polycythemia vera
Essential thrombocytosis
Primary myelofibrosis
JAK2 inhibitor for tx of primary myelofibrosis
ruxolitinib
Peripheral smear finding in CHRONIC LYMPHOCYTIC LEUKEMIA
smudge cells
Daily prophylaxis with WHAT ANTIBIOTIC can prevent INFECTION WITH WHAT in a sickle cell pt?
penicillin prevents Strep pneumo (and other gram+, but encapsulated are most important in sickle cell)
Causes of sideroblastic anemia
1 genetic (enzyme?)
1 acquired
6 reversible
X-linked ALA synthase defect
Myelodysplastic Syndrome
- Alcohol - MCC
- B6 defic. (pyridoxine)
- Pb poisoning
- Chloramphenicol
- Isoniazid
- Cu deficiency
Tx of sideroblastic anemia
B6
cofactor for ALA synthase
Skeletal / x-ray findings in BETA THALASSEMIA MAJOR
Other finding related to hematopoietic issues?
- “crew cut” on skull xray due to MARROW EXPANSION
- chipmunk facies
extramed. hpoiesis > HSM
When does BETA THALASSEMIA MAJOR present and why?
after abt 6 months of life, because HbF (alpha2gamma2) is high until then, then is replaced by HbA2 (alpha2delta2)
Alpha Thalassemia
genetics?
certain kind of genetic change specific to one population + certain kind specific to another
α-globin DELETIONS lead to decreased α-globin synth
the CIS deletions (on same chromosome) occur in ASIANS
the TRANS deletions (on diff. chroms.) occur in AFRICANS
What is the disease and number of globin genes deleted in an asymptomatic carrier for alpha thalassemia?
α-thalassemia “minima”
no anemia, just a silent carrier
(αα / α–) only one α-globin gene deleted
What is the deletion situation in a person with alpha thalassemia minor? And clinical sx?
either TRANS (α–/α–) or CIS (αα/– –)
mild microcytic hypochromic
cis deletion can be worse for offspring
What is Hemoglobin H disease?
genetics? clinical situation?
(– –/α –) 3 α globin genes deleted
excess beta-globin forms beta4 Hb called Hb H
moderate to severe microcytic hypochromic
What is Hemoglobin Barts disease?
genetics? clinical situation?
(– –/– –) ALL four globin genes deleted
excess gamma-globin forms gamma4 Hb
HYDROPS FETALIS, incompat with life
what is the treatment for beta thalassemia major?
what can this cause?
frequent transfusions
can cause secondary hemochromatosis
General difference in bleeding tendencies in…
coagulopathy vs. platelet defects
coagulopathy - DEEP TISSUE bleeding (joints, muscle, subcutis)
platelet - MUCOCUTANEOUS bleeding (epistaxis, petechiae)
Transfusion of PACKED RBCs
tx what 2 conditions?
raise what 2 parameters?
tx acute blood loss and severe anemia
raise Hb and O2 carrying capacity
In platelet transfusion…
how much does each “unit” of plts raise PLT levels approximately?
~ 5000/mm3/unit
3 conditions in which FFP or prothrombin complex concentrate is used
- DIC
- Cirrhosis
- immediate anticoagulation reversal (ie rat poison or warfarin OD)
Difference between
FFP
vs.
Prothrombin complex concentrate
FFP - all coag factors and plasma proteins
PCC - factors II, VII, IX and X plus proteins C/S
What does CRYOPRECIPITATE contain and what does it treat?
fibrinogen (factor I)
factor VIII
factor XIII
vWF
tx deficiencies of fibrinogen and factor VIII (incl. vW disease)
What are the 5 risks of blood transfusion?
think of what blood contains, what blood product containers contain, and blood aging for hints to 3
- Infection (low risk)
- Transfusion reactions (low with proper type)
- Secondary hemochromatosis via Fe overload
- HYPOCALCEMIA - via citrate chelation
- HYPERKALEMIA - via rbc lysis in old blood
Mutations in CHRONIC MYELOMONOCYTIC LEUKEMIA
note: myeloMONOCYTIC not just myelogenous
PDGF-R mutations
Anemia in chronic liver disease
Type?
Peripheral smear?
Severity?
usually NORMO- or slightly MACROCYTIC and MILD (Hb of 10-11 g/dL)
TARGET cells in spear
(microcytic only in <25% of chronic liver disease anemias)
If a patient has microcytic hypochromic anemia, but no uterine bleeding, dark stools or visible stool blood…
what is the most likely cause of anemia?
still IDA despite the lack of noticed blood
still need to do an occult blood test, check ferritin, maybe colonoscopy (especially if older)
(key here is that the lack of blood seen does NOT rule out some GI blood loss somewhere)
Polycythemia vera
dx and tx
- low EPO and cytogenetics (JAK2 mut.)
- phlebotomy (target Hct <45%)
2 tumors OTHER THAN RENAL that can secrete EPO?
cerebellar hemangioblastoma
uterine fibroids (leiomyoma)
Difference in peripheral smear of someone with generally increased serum proteins vs. specifically COLD AGGLUTININS?
general serum protein increase > ROULEAUX (stacked RBCs)
cold agglutinins > CLUMPED rbcs
Diff btwn multiple myeloma and Waldenstrom macroglobulinemia
MM - either IgG or IgA increased; plus CRAB sx
Waldenstrom - IgM is increased causing a HYPERVISCOSITY syndrome (blurred vision, Raynaud)
(remember… MM already has Ms… Waldenstrom needs Ms)
