109 Anemia And Polycythemia Flashcards
Anemia defined
Absolute decrease in circulating RBC
RBC structure
quaternary structure w/ 4 heme polypeptide subunits
bound to an iron molecule that is contained in porphyrin rin
RBC transport of o2 depends on what 3 things?
Hemoglobin
Affinity of oxygen
Flow of blood
What does a left shift of the oxy hemoglobin cube indicate?
Higher binding affinity of o2 and poor offload of tissues
What factors may cause a left shift of the oxy hemoglobin curve to the left (ie high o2 affinity and poor offload at the tissues?)
decrease temp
decrease 2-3 dpo (genetic sometimes)
decrease H ions (ie more basic)
CO
methemoglobin
fetal hbg
What factors may cause a RIGHT shift of the oxy hemoglobin curve to the left (ie low o2 affinity and greater offload at the tissues?)
incr temp
incr 2-3 dpo
incr H –> acidosis
What hormone does anemia stimulate and what does this do?
epo regulates production of rbc and differentiation of erythroid cells to this
stimulated by tissue hypoxia and rbc destruction products
What 4 main cells does the BM stem cells make?
erythroid
myeloid
megakaryocytic
lymphoid
Erythroid cells in BM make ?
rbc
Myleoid cells in BM make ?
granulocyte - baso, neutro, eosinophil and monocytes which in turn go into macrophage
Megakaryocyte cells in BM make ?
plt
Lymphoid cells in BM make ?
t and b cells from small lymphocytes, as well as NK cells
How long do RBC last in circulation?
110-120
Reticulocytes: released every ? d, MCV of __
normal range? (%)
1-3d
mcv 60
1-3%
DDX of MCV <81 (microcytic anemia)
TAILS
thal, anemia ckd, id anemia, lead intox, sideroblastic anemia (ie aud or heavy metals poison)
DDX MCV 81-100 (normocytic anemia)
ABCD: ac bl loss, bm fail, chr dis, destruction (hemolysis)
acute blood loss
ckd
chronic disease overall
hypothyroidism
bm suppression
hemolysis
g6pd
aplastic anemia
DDX of macrocytic anemia
FAT-RBC (fetal hb, alc, thyrd, reticulocytosis-sev hemolysis, b12, cirr)
b12 defic
folate defic
liver disease
reticulocytosis
myelodyspl syndromes
etoh abuse
drugs: hydroxyurea, AZT, chemo agents
What will the findings be for iron, TIBC and ferritin in microytic anemia, with iron deficiency cause?
decr iron
incr tibc
decr ferritin
What findings of ldh and haptoglobin will hemolysis and g6pd present with?
inc ldh
decr haptoglobin
If a coombs test is +, what kind of hemolytic anemia?
autoimm
If a peripheral smear has large oval shaped rbc, hypersegmented neutrophils, think…
b12 or folat defic
If a peripheral smear has schisocytes, helmet cells spherocytes or bite cells, think…
hemolysis
g6pd
If a peripheral smear has microcytic or hypochromic rbc, think…
IDAnemia
thal
sideroblastic anemia
chronic/late disease
What is sideroblastic anemia?
inherited x linked or acquired (isonaizid, chronic etoh, lead poison) where iron accumulates in mitochondria or erythryocyte precursors and heme synthesis is impaired
Acute blood loss clinical features?
tachy
hypot
orthostasis
light headed
dyspnea
pallor
tachypnea
thirst, ams, dec u/o
Hx and PE for clinically severe anemia
hx: out of hosp status/tx
bleeding diathesis
underlying disease
prior transfusion
current meds
trauma y/no
vitals: tachy, hypot, LOC, skin, cv abdo
Skin: petec, ecchymosis, GI, GU
Symptoms of nonacute anemia
ch pain, decr ex tolerance, sob, weak, fatigue, dizzy, syncope
ask re diet, drugs/fhx
bl diathesis possibilities
sites of blood loss at eye, resp, gi, gu, skin jaundice? cardipulmonary, LN
Diagnostic testing for anemia - standard
cbc with diff, retic count and periph smear, rbc indices
type and s vs crossmatch
aPTT INR ptt
lytes
glucose
cr urinalysis for free hemoglobin
Diagnostic testing for anemia - fancy
folate, b12, tsh, retics, dat/coombs
ldh/haptoglobin
When to consider adm for a nonurgent anemia:
- cardiac or neuro sx
- unexplained hbg or hct
- difficulty with f/u
Management of iron deficiency anemia
Ferrous sulfate 325mg PO (65mg elem iron) TID in adults or 2mg/kg/day elem kids
can see some improvement in 24 hours - retics 3-4d child, 1 week adult - full 4-6mo
Thalassemia: what is a normal HbA made up of ?
2 alpha paired globin chains
2 beta paired chains
Thalassemia: what is a normal Hbfetal made up of ?
2 alpha 2 gamma
Thalassemia: what is this?
AR - synthesis of abn globin chains in various combinations which can cause a hemolytic anemia as they apoptos, decr synthesis and ineff erythpropoeisis
Beta thalassemia what is this?
reduced/absent beta globulin synthesis w/ excess alpha globins
can be silent ie carrier, minor or major
Tx major beta thal?
transfusion or chelation dependent
Alpha thalassemia: what is this?
reduced/abs alpha globin w/ excess of beta globulins
Hemoglobin H is B globin tetramer vs Hemoglobin Bart
What are the transfusion dep thalassemias?
thal major
severe hbg E/beta thal, Hbg barts hydrops
need to survive
What are the non transfusion dep thalassemias?
thal minor
mild hbgE
HbH, alpha thal trait
range no transf to intermittent
Clinical features of b chain thalassemia - when to consider?
Mediterranian pop - sev anemia, hepatosplenomegaly, jaundice, abn development and prem death
usually by 2y
transfusion dep - risk of iron OD in tissue so require chelator
Clinical features of heterozyg beta thalassemia/thal minor- when to consider?
some functional beta chains so a mild anemia, usually asx with no transfusion
Clinical features of alpha chain thalassemia - when to consider given how many alpha thal are abnormal (1-4)
asx carrier - prenatal death
silent carrier - one missing gene
alpha thal trait 2- missing genese
Hemoglobin H - 3 missing mild mod anemia
Hb barts all 4 abn alpha genese = hydrops fetalis and fetal death
Thalasemia testing
microcytic anemia
hypochromic on peripheral smear with target cells and basophilic stippling
needs electrophoresis and genetic testing
Silent carrier, beta thal minor and alpha trait thal - tx?
none
unless times of high stress like infection, pregnancy, surgery, low hbg
Treatment of transfusion dep thalssemias?
transfusion, for goals of correcting anemia, suppressing ineff epo, inhibit incr gi abrorp
q2-5 weeks to aim for 90-105
Transfusion dependent thalssemias: what to do in terms of iron chelators?
deferoxamine, deferiprone, deferasirox
Why give hydroxyurea in some Non transfusion dependent thals?
cytotoxic antimetabolite incr the fetal hemoglobin
Non and Transfusion dependent thalssemias: type of surgery vs longer term/more invasive management strategies?
splenectomy
hematopoeitc stem cell transplant
Sideroblastic anemia: defect in ? synthesis
porphyrin
Sideroblastic anemia: idiopathic - what to worry about in elderly?
common cause refractory anemia elderly and may be pre leukemic state
Sideroblastic anemia: acquired examples
chloramphenicol, isonaizid, linezolid, penicillamine
myelodyspl syndrome or myeloprolif disorders
etoh
copper defic, lead poison, zinc tox
Sideroblastic anemia: pathophysiology
impairs ability to make hbg and the excess iron ends up in mitochondria
Sideroblastic anemia: levels of serum iron, ferritin, tsat?
all high
Sideroblastic anemia: characteristic smear?
ringer sideroblasts - at least 5 on prussian blue stain which is ++ erythroid precursor
Sideroblastic anemia: management of congenital/acquired (as most times tx is tx underlying)
pyridoxine (B6) and responds to tx with 100mg PO TID
sometimes ongoing transfusion and chelation
soemtimes st transplant if congenital or myelodysplastic
Anemia of CKD: what happens to RBC and erythropoesis?
reduced making and survival time as hostile inflamm environment
Anemia of CKD: 5 causes
malignancy
arthritis
renal insuff
HF
copd
chronic infection
Anemia of CKD: diagnostic testing and lab values of serum iron, tibc, ferritin and BM
cbc mcv
low serum iron
low TIBC
normal/elevated ferritin
normal BM
Megaloblastic anemia 2 main causes
folate
f12
Non megaloblastic causes - name 5
etoh
liver dysfunc
hypothyroid
myelodysplastic syndromes
drug: hydroxyurea, methotrexate, zidovudine, vpa
Vi B12 defic clinical findings
paresthesia hand and feet, decreased proprioception, vibratory sense, weakness/spasticity of LE
can be forgetful, depressed, paranoid
degen of SC due to loss myelin in dorsal and lateral column - movement related *ataxia
What aspect of vit b12 deficiency does folate deficiency present with?
neuropsych
Diagnostic testing of a megaloblastic anemia
mcv >100
peripheral smear: large oval red cell, anisocytosis
hypersegm PMN
elevated LDH
b12 and folate levels
How to treat folate defic
1mg oral folic acid/day
How to treat B12 deficiency?
check out causes of malabsorption
Parenteral 1000mcg IM daily 7-10d then q1mo
Aplastic anemia causes - non infectious, name 5
chloramphenicol
phenylbutazone
anticovulsants
insecticides
solvents
sulfoonamides
gold
benzene
Aplastic anemia name 5 non drug causes
autoimm
viral hepatits
radiation exposure
viral illness - parvo b12, hiv, ebv
What med to avoid in aplastic anemia?
aspirin
What is a myelodysplastic syndrome?
class hematopoetic stem cell disorder characterized by cytopenia, myelodysplasia, ineffective hematopoesis that oncogenic mutations cause
myelodysplastic syndrome on BM bx - findings?
dysplastic cell lines
blast cells
Myeloproliferative sydromes - what is primary myelofibrosis?
primary BM fibrosis, splenomegaly due to extramedullary hematopoeisis –> can transform to leukemia
Clinical features of hemolytic anemia in general?
sx of anemia
new jaundice, hematuria, fever, hepatosplenomegaly, abdo/back pain, AMS
Hemolytic anemia: make sure you ask about …
fam hx
pmhx
How does intravascular hemolysis pathophys work?
decr o2 carrying capacity, release of free hemoglobin that binds to haptoglobin and hemopexin, to liver, conjugated to bili and extcreted = jaundice
this system gets overwhelmed = hemoglobinuria, hemoglobinemia
What are some general causes of intravascular hemolysis?
abo incompatibility
autoimmune hemolytic anemias
infection
DIC
toxins
What are some causes of extravascular hemolysis?
hereditary spherocytosis
g6pd
scd
autoimmune
Name 5 causes of intrinsic hemolytic anemia
PK defic, g6pd
spherocytosis, PNH
hemoglobinopathies, thal
Name 5 causes of extrinsic hemolytic anemia
alloantibodies/auto
microangiopathic hemolytic anemia, prosth heart valve
drugs
toxins
infections
thermal
abnormal sequestration
G6PD - how does this cause intravascular hemolysis?
glutathion needed to protect hemoglobin from oxidant injury - some AA or medit decent to not have this
Drugs causing incr hemolysis in G6PD - name 5
aspirin
primaquine
quinine
nitrofurantoin
sulfamethoxazole
sulfones
fava beans
methylene blue
nalidixic acid
Hereditary spherocytosis: what is this?
AD mutation in gene so the RBC membrane is shaped as a sphere and thus easily friable by spleen
Hereditary spherocytosis: how to tx?
supportive
they probably RQ splenectomy >6y if severe
Hereditary spherocytosis: MCHC and RDW?
incr
Paroxysmal nocturnal hemoglobinemia (PNH): what is this?
stem cell defect causing abnormal erythrocyte, neutrophil and plt sn to complement
Paroxysmal nocturnal hemoglobinemia (PNH): name 4 causes
chronic hemolysis
hemosiderinuria
leukopenia
low plt
Paroxysmal nocturnal hemoglobinemia (PNH): lab findings - smear, cooms, Ham test?
n, neg
ham - normal activation with complement with use sucrose or acid hemolysis
Paroxysmal nocturnal hemoglobinemia (PNH): key complication?
thrombosisc of hepatic vein
Paroxysmal nocturnal hemoglobinemia (PNH): tx
support
eculizumab
ABO incompatibility: how does this work?
IgM abodies act as hemolysin causing agglutination of RBC and fixation of complement so you get intravascular hemolysis
Rh incompatibility how does this work for hemolytic anemia?
IgG causes accelerated destruction of RBC by spleen/liver
Diseases assoc with autoimmune hemolytic anemias: name 4 categories
neoplasm
collagen vascular disease
infections
misc - thyroid, uc, drug immune reactions
Diseases assoc with autoimmune hemolytic anemias: neoplasms
mlaign: CLL, lymphoma, myeloma, thymom, CML
benign - teratoma, dermoid cyst
Diseases assoc with autoimmune hemolytic anemias: collagen vascular disease
sle
periarteritis nodosa
RA
Diseases assoc with autoimmune hemolytic anemias: infections
mycoplasma
syphilis
virus: mono, hepatitis, influenza, coxsackie, cmv
Autoimmune hemolytic anemia - warm type often seen in?
yo female
Autoimmune hemolytic anemia - warm - how does this occur?
variable complement fixation, + DAT for IgG as it binds to Rh, is removed by macrophages and sequested in spleen
Autoimmune hemolytic anemia - warm tx
supportive - manage underlying
GC, rituximab
second line is things heme gives IVIG< plex
and surgery for splenectomy
Autoimmune hemolytic anemia - cold - who is this seen in?
old men
Autoimmune hemolytic anemia - cold - how does this occur?
IgM complement fixation which react with surface ag at low temps and cause either intra or extra vascular hemolysis upon rewarming
Autoimmune hemolytic anemia - cold - 3 common diseases?
ebb
mycoplasma
lymphoma
Autoimmune hemolytic anemia - cold - DAT ?
+
Autoimmune hemolytic anemia - cold - tx
supportive with folate and vit b12 if defic
avoid trigger
underlying disease tx
Autoimmune hemolytic anemia - cold - complication?
thrombosis - may consider thromboprophylaxis with acute exacerbations or for chronic disease in high risk situations
Extrinsic cause of hemolysis: how does microangiopathic hemolytic anemia occur?
microcirculatory fragments by threads of fibrin deposited in arterioles
microangiopathic hemolytic anemia - underlying disease- list 6
malign htn
preeclampsia
vasculitis
ttp
purpura
dic
vascular anomalites
Extrinsic cause of hemolysis: Cardiac - how does this occur?
shearing from turbulance - ie valves, av fistula, AS, LS heart lesion
Extrinsic cause of hemolysis: march hemoglobinemia
breaking IV rbc by repetitive pounding - soldiers and marathoners
What are environmental/toxin causes of hemolysis? List 7
burns
freshwater drown
hyperthermia
brown recluse spider
venomous snake bite
castor beans
mushrooms
malaria
bartonella
clostridium
What is a DAT test for ?
hemolytic anemia - detects abodies or complement on human rbc membranes by adding a reagant that detects igG, A M or complement
How to temporize/slow hemolysis - drug?
prednisone 1mg/kg
What is sickle cell disease?
AR mutation producing HbS as a mutation in he beta globin gene
In sickle cell, what happens to rbc when exposed to deoxygenation or various stressors?
rbc sickles, rigid so that blood becomes sludge, undergoes sequestration in liver and spleen
Sickle cell disease: complications list 6
vaso occlusive events
chronic hemolysis
thrombosis
organ injury - renal papillary necorsis, splenic infarct, PE, traumatic hyphema, exertional rhabdo, sudden cardiac death
Sickle cell disease: when to consider life threatening aplastic crisis?
hbg <20 after previously stable and retic count <2% -
*can occur after suppression epoesis infection or folate defici
Sickle cell disease: Acute vaso occlusive event: precip factors?
antecedent infection
cold exposure
stress/trauma
Painful Sickle cell disease crisis - what happens?
origin in tissue ischemia which leads to irev sickling, more sludge and obstruction
Painful Sickle cell disease crisis which body parts typically involved?
abdo
chest
back
extremities
Sickle cell disease neuro diseases?
tia
cerebral infarct
ich
scinfarct
vestibular
hearing issue
What is an acute chest syndrome?
SCD: fever cough hypoxia, chest pain, sob and new infiltrate on cxr
look for mycoplasma/chlam infection
When does autoinfarction of spleen occur in kids with sickle cell?
10-27mo
Functional asplenia in sickle cells kiddos: 1mo-5y how to tx?
amox/pen
What bugs are people with scd more at risk for getting?
encapsulated organisms
salmonella om!!
Treating a sickle cell patient - important considerations:
- hydroxyurea: induces HbgF, reduces pain crisis and need blood transfusion
- transfusion for severe exacerbation with evidence of hypoxia/hypoperfusion, acute organ damage, preop
- exchange transfusion if acute chest syndrome, stroke, asplastic crisis, acute splenic sequestration
- stem cell transplant: cure!!
Acute pain crisis tx
analgesia
nsaids
ivf
Stroke in SCD pt:
exchange transfusion with goal hbs <30% and hbg of 10
tpa in adults also consideration
Acute chest syndrome management of scd:
hydration
analgesia
oxygenate/ventil
CTX and azithromycin
exchange transf if multilobe involvemnt or worsening hypoxemia, neuro abn, multi organ involvement
What GU concern is more common in SCD?
priapism - aspirate blood and irrigate with alpha adrenergic agent
What are the symptoms of polycythemia?
mild headache
vertigo/dizzy, blurry vision due to vol oload
hyperviscosity: thrombosis, plt dysfunc (epistaxis, spont bruising, GIB)
What are the signs of polycythemia?
plethoric skin/mm
optic fundal venous congestions
splenomegaly
hf
Causes of absolute erythrocytosis: list 8
R to L shunt
pulmonary disease
carboxyhemoglobinemia
high alt acclim
sleep apnea
high affnity hemoglobins
FSGS, renal transplant
hepatoma, adrenal tumor, meningioma, pheo, PV
meds: steroids
Causes of absolute erythrocytosis: list 5
emesis, diarrhea, diuretics, burns, low albumin
chronic plasma contraction: hypoxia, hypertension, tobacco or etoh use
What is primary polycythemia vera?
chronic myeloprolif disorder caused by JAK2mutation
polycythemia vera: symptoms
h/a
weak
dizzy
excess sweat
plethora
pruritis after hot water exposure
polycythemia vera list 3 complications of disease
cva, mi, dvt
bleeding
risk leukemic or fibrotic transformation
Labs: polycythemia vera
all cell lines involved and typically big with elevated hbg, rbc mass, plt and wbc big
polycythemia vera diagnostic criteria
hemoglobin >16.5 in men, 16 in wo or hct >49% men, 48% wo or incr rbc mass
bm trilineage prolif with pleom mature megakaryocytes
jak2 mutation
polycythemia vera tx
- phlem to hct <45%
- daily aspirin 40-100mg po for primary prevention thrombosis
- high risk (hx thrombosis, age >60: hydroxyurea 500mg po bid
Secondary polycythemia: defn?
appropr epo response to abn tissue oxygen levels (ie excluded by N art o2 sat)
Secondary polycythemia: emergent tx
phlebotomy - 500ml and replace with saline same
true emerg = 1-1.5L of blood over 24 hour period
