Anemia Flashcards
5 physiologic factors in Hb level
age
sex (M higher) / puberty (higher w testosterone)
altitude (higher)
genetics (African less)
Anemia DDx by micro/normomacro-cytic
Microcytic: thal, chr dis, IDA, lead, sideroblastic
Normocytic: blood loss, suppression/BMF, hemolysis, splenic sequestration, CKD
Macrocytic: megaloblastic, BMFS, drugs, hypothyroid, liver, T21
define MCV, RDW, MCHC and role in thal vs IDA
MCV: mean corpuscular volume; diameter of cells
RDW: red cell distribution width; variability in cell volume
MCHC: mean corpuscular Hb concentration; cell density
MCV low in both, MCHC low in both
RDW high in IDA
reasons for false high/low Hb on automated counter
high: dehydration, lipemia, leukocytosis, nRBC, prolonged tourniquet
low: clotting, overfilled tube, dilutional, agglutinin, hemolysis
5 steps of iron metabolism
ferrireductase Fe3+ to 2+
DMT1 transports across duodenal epithelium
Ferroportin exports across membrane
Hephaestin Fe 2+ to Fe 3+
Transferrin bound for transport in blood
iron deficiency ddx
diet: excessive cows milk, low fe (vegan)
blood loss: GI, menorrhagia
malabsorption: Celiac, IBD, gastric bypass, antacid therapy, tannins, metal (Co, Pb)
Poor stores: pregnancy, infancy/prem, inflammation
Inadequate presentation: atransferrinemia, anti-transferrin receptor Ab
IRIDA mutation (TMPRSS6)
IV Fe indications
CKD
PO intolerance/ineffective
need rapid response
malabsorption
IRIDA
Fe supplementation recovery timeline
1-2w: retic
1mo: Hb
1-3mo: MCV/RDW
3mo: ferritin
Physiologic Hb nadir etiology
decline of g chains
drop in EPO due to higher O2 concentrations
High iron foods
Meat: beef, liver, fish
legumes: chick peas, black beans, lentils
leafy greens: spinach, broccoli
tofu
fortified infant formula/cereals
IDA smear findings
hypochromic microcytic anemia
anisopoikilocytosis
reticulocytopenia
thrombocytosis
pencil cells
IDA non-heme S/S
impaired immunity
neurocognitive
nail changes
pica
glossitis
restless leg
hemochromatosis genetics
aut rec
homeostatic iron regulator (HFE) most common mutation (C282Y > H63D)
Juvenile: hepcidin (HAMP), hemojuvelin (HJV)
Adult: transferrin receptor 2 (TFR2), ferroportin (FPN1)
B12 deficiency DDx
diet: vegan/veg
Pernicious anemia (IF deficiency)
competition: tapeworm, blind intestinal loop
Decreased receptors: ileal resection, IBD, Celiac, H pylori
Imerslung-Grasbeck Syndrome (aut rec B12 malabsorption)
Imerslung-Grasbeck Syndrome
aut rec
B12 deficiency
Lack of IF binding
Intravascular vs extravascular hemolysis DDx
intravascular:
- enzymopathy: G6PD, PKD
- Cold AIHA: PCH, CAD
- MAHA: TMA, DIC, HUS/TTP, artificial heart valve, Kasabach Merritt
Extravascular:
- warm AIHA
- HDN
- membranopathy: HS, HE, Rh null, xerocytosis
- Hbopathies: SCD, thal, unstable Hb
- toxin, infection, burn
- Wilson
hemolytic anemia smear findings
normocytic anemia
reticulocytosis
schistocytes
basophilic stippling
Howell-Jolly bodies
Heinz bodies
Heinz bodies: define and DDx
precipitated denatured Hb
G6PD
unstable Hb
hemolysis
oxidant drugs
Howell-Jolly Body: define and DDx
nuclear remnant - larger than pappenheimer
thal
hypo/asplenia
hemolysis
megaloblastic anemia
Basophilic stippling: define and DDx
ribosomal/residual RNA remnants
thal
SCD
lead
sideroblastic
megaloblastic
Pappenheimer: define and DDx
1-2 irregular small granules of iron deposits
thal
sideroblastic
megaloblastic
hemolysis
post splenectomy
HS lab findings
spherocytes
elevated RDW, MCHC
extravascular hemolysis
reticulocytosis
EMA flow cytometry
elevated osmotic fragility
HS genetics
vertical interactions
aut dom: ankyrin, Band 3, b spectrin
aut rec: a spectrin, protein 4.2
HE genetics
horizontal interactions
aut dom
Spectrin or band 4.1
what is pyropoikilocytosis
subtype of HE
aut rec spectrin abnormalities
smear with bizarre shapes
Hereditary Stomatocytosis: DDx and subtypes
DDx: artifact, hereditary, ethanol, Rh null, Tangier, drugs
Overhydrated
- aut dom stomatin or band 7.2 mutations
- low MCHC, positive osmotic fragility
Xerocytosis
- aut dom PIEZO1 or KCNN4 mutations
- high MCHC, decreased osmotic fragility
G6PD deficiency pathophys and genetics
G6PD generates NADPH, which protects against oxidative injury
X linked
G6PD deficiency triggers
fava beans
drugs: Vit C, sulpha, dapsone, methylene blue, rasburicase, nitrofurantoin
infection
describe direct and indirect Coombs
DAT: anti-human IgG binds to RBC-bound IgG –> ?agglutination
indirect: donor RBC and reagant added to serum –> ?agglutination
what is positive in warm vs cold AIHA
Warm: IgG +- C3 ; 70% bispecific
CAD: C3 (IgM or anti-I/i)
PCH: C3 (IgG, anti-P) -> Donath Landsteiner test
Microangiopathic anemia ddx
DIC
HUS
TTP
TMA
Kasabach-Merrit
mechanical heart valve
Inf, burn, drugs
warm AIHA etiol and tx
Primary (50%)
Secondary
- immune: evans, SLE, thyroiditis, hepatitis, Graves, T1DM
- immunodeficiency
- ALPS
- malig, infection, drugs
steroid, transfusions
- 2nd line: IVIG, ritux, splenectomy
CAD etiol and tx
Mycoplasma (anti-I)
EBV (anti-i)
supportive
plasmapheresis
which are extravascular vs intravascular?
PCH
CAD
PNH
warm AIHA
Extravascular: warm AIHA and CAD
Intravascular: PCH and PNH
PCH etiol and tx
anti-P
Donath Landsteiner positive
supportive
PNH etiol, dx, tx
clonal X linked PIG-A gene (PG1 protein)
CD 55/59 negative
Eculizumab
HSCT
Polycythemia ddx
relative: dehydration, smoking
Primary:
- EPO-R activating mutation (aut dom)
- PCV (JAK2 mutation)
- congenital methemoglobinemia
- high O2 affinity Hb
Secondary (elevated EPO)
- hypoxia: altitude, OSA, obesity
- renal artery stenosis
- tumors: RCC, HCC, pheo, etc
- exogenous EPO: steroid, NO
- toxin: CO, smoking
- neonatal: IDM, eclampsia, IUGR, T21, TTTS
Polycythemia Tx
observation
phlebotomy
symptomatic -> ASA
JAK2 mutation -> HU
spherocyte DDx
HS
AIHA
MAHA
thermal injury
liver disease
clostridial sepsis
HDFN
hypersplenism
severe hypophosphatemia
TTP pentad
fever
MAHA
thrombocytopenia
renal dysfunction
neurologic changes
TTP pathophysiology and tx
lack of ADAMTS13
ultralarge VWF multimers present
fibrin deposition and plt trapping
microangiopathy
pulse MP
ritux
FFP
plasmapheresis x 5d course
caplacizumab
Upshaw-Schulman Syndrome
congenital ADAMTS13 deficiency, aut rec
high suspicion of FA, chromosome breakage negative. Next step
skin fibroblast culture
neonatal hyperbili DDx
HDFN (Rh > ABO)
Sepsis
dehydration
G6PD
HS
Crigler-Najjar
main iron absorption regulator
hepcidin
created in liver
decreases absorption by inhibiting ferroportin from transporting Fe out of duodenal epithelium and macrophages
What is IRIDA
Iron refractory IDA
TMPRSS6 mutation (aut rec)
hepcidin upregulation (i.e. decreased absorption)
megaloblastic anemia BM findings
nuclear-cytoplasmic dys-synchrony in erythroid precursors
hypercellular
giant metamyelocytes
difference in presentation b/w B12 and folate deficiencies
B12: neuro findings
- posterior column degeneration: proprioceptive, fine motor, ataxia, psychomotor retardation, seizures, depression, psychosis
Lab differentiation of B12 and folate deficiencies
Homocysteine elevation in both
MMA elevation in B12 only
Evan’s Syndrome dx, tx
any combo of ITP, AIHA, autoimmune neutropenia with chronic remitting/relapsing course
CS +- IVIG
2nd line: ritux, CSA, MMF, VCR, danazol, splenectomy
warm AIHA tx
steroid pulse –> pred 1-2 mg/kg/d x 2-4w –> taper over 3-12mo
2nd line: IVIG (40% response), ritux (90% CR), splenectomy (2/3 partial response)
Associated anemia:
- anti-P
- anti-I
- anti-i
anti-P: PCH
anti-I: Mycoplasma CAD
anti-i: EBV CAD
define Donath Landsteiner
DL Ab: IgG biphasic hemolysin that binds RBC and fixes complement at low temp, but only causes hemolysis near 37C
PCH tx
self-limiting
supportive: avoid cold
CAD tx
self-limiting
supportive: avoid cold
plasmapheresis if severe
HDFN prevention
RhIg to Rh neg mothers given at 28w, delivery, post invasive procedure
horizontal vs vertical membranopathy
horizontal: HE (E lines are horizontal)
vertical: HS (S goes from top to bottom)
SE Asian Ovalocytosis epi, pathophys, ix
Melanesia, Malaysia, Indonesia, Philippines
aut dom band 3 deletion
theta cells sens/spec 94/99%
low EMA
examples of unstable Hb
Hb Koln: high O2 affinity
Hb Zurich: increased CO affinity
Hb Poole: unstable g chain
Hb Hammersmith: unstable b chain with low O2 affinity
TTP px
mortality 80% w/o therapy
mortality 10-20%
relapse rate 20-30%
HUS triad
MAHA
thrombocytopenia
renal dysfunction
HUS Ix
intravascular hemolysis with schistocytes
mild-mod thrombocytopenia
normal INR, PTT, fibrinogen
ADAMTS13 normal
