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109 Anemia And Polycythemia Flashcards

1
Q

Anemia defined

A

Absolute decrease in circulating RBC

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2
Q

RBC structure

A

quaternary structure w/ 4 heme polypeptide subunits
bound to an iron molecule that is contained in porphyrin rin

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3
Q

RBC transport of o2 depends on what 3 things?

A

Hemoglobin
Affinity of oxygen
Flow of blood

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4
Q

What does a left shift of the oxy hemoglobin cube indicate?

A

Higher binding affinity of o2 and poor offload of tissues

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5
Q

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?)

A

decrease temp
decrease 2-3 dpo (genetic sometimes)
decrease H ions (ie more basic)
CO
methemoglobin
fetal hbg

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6
Q

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?)

A

incr temp
incr 2-3 dpo
incr H –> acidosis

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7
Q

What hormone does anemia stimulate and what does this do?

A

epo regulates production of rbc and differentiation of erythroid cells to this

stimulated by tissue hypoxia and rbc destruction products

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8
Q

What 4 main cells does the BM stem cells make?

A

erythroid
myeloid
megakaryocytic
lymphoid

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9
Q

Erythroid cells in BM make ?

A

rbc

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10
Q

Myleoid cells in BM make ?

A

granulocyte - baso, neutro, eosinophil and monocytes which in turn go into macrophage

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11
Q

Megakaryocyte cells in BM make ?

A

plt

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12
Q

Lymphoid cells in BM make ?

A

t and b cells from small lymphocytes, as well as NK cells

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13
Q

How long do RBC last in circulation?

A

110-120

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14
Q

Reticulocytes: released every ? d, MCV of __
normal range? (%)

A

1-3d
mcv 60
1-3%

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15
Q

DDX of MCV <81 (microcytic anemia)

A

TAILS
thal, anemia ckd, id anemia, lead intox, sideroblastic anemia (ie aud or heavy metals poison)

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16
Q

DDX MCV 81-100 (normocytic anemia)

A

ABCD: ac bl loss, bm fail, chr dis, destruction (hemolysis)
acute blood loss
ckd
chronic disease overall
hypothyroidism
bm suppression
hemolysis
g6pd
aplastic anemia

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17
Q

DDX of macrocytic anemia

A

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

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18
Q

What will the findings be for iron, TIBC and ferritin in microytic anemia, with iron deficiency cause?

A

decr iron
incr tibc
decr ferritin

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19
Q

What findings of ldh and haptoglobin will hemolysis and g6pd present with?

A

inc ldh
decr haptoglobin

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20
Q

If a coombs test is +, what kind of hemolytic anemia?

A

autoimm

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21
Q

If a peripheral smear has large oval shaped rbc, hypersegmented neutrophils, think…

A

b12 or folat defic

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22
Q

If a peripheral smear has schisocytes, helmet cells spherocytes or bite cells, think…

A

hemolysis
g6pd

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23
Q

If a peripheral smear has microcytic or hypochromic rbc, think…

A

IDAnemia
thal
sideroblastic anemia
chronic/late disease

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24
Q

What is sideroblastic anemia?

A

inherited x linked or acquired (isonaizid, chronic etoh, lead poison) where iron accumulates in mitochondria or erythryocyte precursors and heme synthesis is impaired

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25
Q

Acute blood loss clinical features?

A

tachy
hypot
orthostasis
light headed
dyspnea
pallor
tachypnea
thirst, ams, dec u/o

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26
Q

Hx and PE for clinically severe anemia

A

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

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27
Q

Symptoms of nonacute anemia

A

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

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28
Q

Diagnostic testing for anemia - standard

A

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

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29
Q

Diagnostic testing for anemia - fancy

A

folate, b12, tsh, retics, dat/coombs
ldh/haptoglobin

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30
Q

When to consider adm for a nonurgent anemia:

A
  1. cardiac or neuro sx
  2. unexplained hbg or hct
  3. difficulty with f/u
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31
Q

Management of iron deficiency anemia

A

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

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32
Q

Thalassemia: what is a normal HbA made up of ?

A

2 alpha paired globin chains
2 beta paired chains

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33
Q

Thalassemia: what is a normal Hbfetal made up of ?

A

2 alpha 2 gamma

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34
Q

Thalassemia: what is this?

A

AR - synthesis of abn globin chains in various combinations which can cause a hemolytic anemia as they apoptos, decr synthesis and ineff erythpropoeisis

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35
Q

Beta thalassemia what is this?

A

reduced/absent beta globulin synthesis w/ excess alpha globins

can be silent ie carrier, minor or major

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36
Q

Tx major beta thal?

A

transfusion or chelation dependent

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37
Q

Alpha thalassemia: what is this?

A

reduced/abs alpha globin w/ excess of beta globulins
Hemoglobin H is B globin tetramer vs Hemoglobin Bart

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38
Q

What are the transfusion dep thalassemias?

A

thal major
severe hbg E/beta thal, Hbg barts hydrops

need to survive

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39
Q

What are the non transfusion dep thalassemias?

A

thal minor
mild hbgE
HbH, alpha thal trait

range no transf to intermittent

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40
Q

Clinical features of b chain thalassemia - when to consider?

A

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

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41
Q

Clinical features of heterozyg beta thalassemia/thal minor- when to consider?

A

some functional beta chains so a mild anemia, usually asx with no transfusion

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42
Q

Clinical features of alpha chain thalassemia - when to consider given how many alpha thal are abnormal (1-4)

A

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

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43
Q

Thalasemia testing

A

microcytic anemia
hypochromic on peripheral smear with target cells and basophilic stippling

needs electrophoresis and genetic testing

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44
Q

Silent carrier, beta thal minor and alpha trait thal - tx?

A

none

unless times of high stress like infection, pregnancy, surgery, low hbg

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45
Q

Treatment of transfusion dep thalssemias?

A

transfusion, for goals of correcting anemia, suppressing ineff epo, inhibit incr gi abrorp

q2-5 weeks to aim for 90-105

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46
Q

Transfusion dependent thalssemias: what to do in terms of iron chelators?

A

deferoxamine, deferiprone, deferasirox

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47
Q

Why give hydroxyurea in some Non transfusion dependent thals?

A

cytotoxic antimetabolite incr the fetal hemoglobin

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48
Q

Non and Transfusion dependent thalssemias: type of surgery vs longer term/more invasive management strategies?

A

splenectomy
hematopoeitc stem cell transplant

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49
Q

Sideroblastic anemia: defect in ? synthesis

A

porphyrin

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50
Q

Sideroblastic anemia: idiopathic - what to worry about in elderly?

A

common cause refractory anemia elderly and may be pre leukemic state

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51
Q

Sideroblastic anemia: acquired examples

A

chloramphenicol, isonaizid, linezolid, penicillamine

myelodyspl syndrome or myeloprolif disorders

etoh

copper defic, lead poison, zinc tox

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52
Q

Sideroblastic anemia: pathophysiology

A

impairs ability to make hbg and the excess iron ends up in mitochondria

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53
Q

Sideroblastic anemia: levels of serum iron, ferritin, tsat?

A

all high

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54
Q

Sideroblastic anemia: characteristic smear?

A

ringer sideroblasts - at least 5 on prussian blue stain which is ++ erythroid precursor

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55
Q

Sideroblastic anemia: management of congenital/acquired (as most times tx is tx underlying)

A

pyridoxine (B6) and responds to tx with 100mg PO TID

sometimes ongoing transfusion and chelation

soemtimes st transplant if congenital or myelodysplastic

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56
Q

Anemia of CKD: what happens to RBC and erythropoesis?

A

reduced making and survival time as hostile inflamm environment

57
Q

Anemia of CKD: 5 causes

A

malignancy
arthritis
renal insuff
HF
copd
chronic infection

58
Q

Anemia of CKD: diagnostic testing and lab values of serum iron, tibc, ferritin and BM

A

cbc mcv
low serum iron
low TIBC
normal/elevated ferritin
normal BM

59
Q

Megaloblastic anemia 2 main causes

A

folate
f12

60
Q

Non megaloblastic causes - name 5

A

etoh
liver dysfunc
hypothyroid
myelodysplastic syndromes
drug: hydroxyurea, methotrexate, zidovudine, vpa

61
Q

Vi B12 defic clinical findings

A

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

62
Q

What aspect of vit b12 deficiency does folate deficiency present with?

A

neuropsych

63
Q

Diagnostic testing of a megaloblastic anemia

A

mcv >100
peripheral smear: large oval red cell, anisocytosis
hypersegm PMN

elevated LDH
b12 and folate levels

64
Q

How to treat folate defic

A

1mg oral folic acid/day

65
Q

How to treat B12 deficiency?

A

check out causes of malabsorption

Parenteral 1000mcg IM daily 7-10d then q1mo

66
Q

Aplastic anemia causes - non infectious, name 5

A

chloramphenicol
phenylbutazone
anticovulsants
insecticides
solvents
sulfoonamides
gold
benzene

67
Q

Aplastic anemia name 5 non drug causes

A

autoimm
viral hepatits
radiation exposure
viral illness - parvo b12, hiv, ebv

68
Q

What med to avoid in aplastic anemia?

A

aspirin

69
Q

What is a myelodysplastic syndrome?

A

class hematopoetic stem cell disorder characterized by cytopenia, myelodysplasia, ineffective hematopoesis that oncogenic mutations cause

70
Q

myelodysplastic syndrome on BM bx - findings?

A

dysplastic cell lines
blast cells

71
Q

Myeloproliferative sydromes - what is primary myelofibrosis?

A

primary BM fibrosis, splenomegaly due to extramedullary hematopoeisis –> can transform to leukemia

72
Q

Clinical features of hemolytic anemia in general?

A

sx of anemia
new jaundice, hematuria, fever, hepatosplenomegaly, abdo/back pain, AMS

73
Q

Hemolytic anemia: make sure you ask about …

A

fam hx
pmhx

74
Q

How does intravascular hemolysis pathophys work?

A

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

75
Q

What are some general causes of intravascular hemolysis?

A

abo incompatibility
autoimmune hemolytic anemias
infection
DIC
toxins

76
Q

What are some causes of extravascular hemolysis?

A

hereditary spherocytosis
g6pd
scd
autoimmune

77
Q

Name 5 causes of intrinsic hemolytic anemia

A

PK defic, g6pd
spherocytosis, PNH
hemoglobinopathies, thal

78
Q

Name 5 causes of extrinsic hemolytic anemia

A

alloantibodies/auto
microangiopathic hemolytic anemia, prosth heart valve
drugs
toxins
infections
thermal
abnormal sequestration

79
Q

G6PD - how does this cause intravascular hemolysis?

A

glutathion needed to protect hemoglobin from oxidant injury - some AA or medit decent to not have this

80
Q

Drugs causing incr hemolysis in G6PD - name 5

A

aspirin
primaquine
quinine
nitrofurantoin
sulfamethoxazole
sulfones
fava beans
methylene blue
nalidixic acid

81
Q

Hereditary spherocytosis: what is this?

A

AD mutation in gene so the RBC membrane is shaped as a sphere and thus easily friable by spleen

82
Q

Hereditary spherocytosis: how to tx?

A

supportive
they probably RQ splenectomy >6y if severe

83
Q

Hereditary spherocytosis: MCHC and RDW?

A

incr

84
Q

Paroxysmal nocturnal hemoglobinemia (PNH): what is this?

A

stem cell defect causing abnormal erythrocyte, neutrophil and plt sn to complement

85
Q

Paroxysmal nocturnal hemoglobinemia (PNH): name 4 causes

A

chronic hemolysis
hemosiderinuria
leukopenia
low plt

86
Q

Paroxysmal nocturnal hemoglobinemia (PNH): lab findings - smear, cooms, Ham test?

A

n, neg
ham - normal activation with complement with use sucrose or acid hemolysis

87
Q

Paroxysmal nocturnal hemoglobinemia (PNH): key complication?

A

thrombosisc of hepatic vein

88
Q

Paroxysmal nocturnal hemoglobinemia (PNH): tx

A

support
eculizumab

89
Q

ABO incompatibility: how does this work?

A

IgM abodies act as hemolysin causing agglutination of RBC and fixation of complement so you get intravascular hemolysis

90
Q

Rh incompatibility how does this work for hemolytic anemia?

A

IgG causes accelerated destruction of RBC by spleen/liver

91
Q

Diseases assoc with autoimmune hemolytic anemias: name 4 categories

A

neoplasm
collagen vascular disease
infections
misc - thyroid, uc, drug immune reactions

92
Q

Diseases assoc with autoimmune hemolytic anemias: neoplasms

A

mlaign: CLL, lymphoma, myeloma, thymom, CML
benign - teratoma, dermoid cyst

93
Q

Diseases assoc with autoimmune hemolytic anemias: collagen vascular disease

A

sle
periarteritis nodosa
RA

94
Q

Diseases assoc with autoimmune hemolytic anemias: infections

A

mycoplasma
syphilis
virus: mono, hepatitis, influenza, coxsackie, cmv

95
Q

Autoimmune hemolytic anemia - warm type often seen in?

A

yo female

96
Q

Autoimmune hemolytic anemia - warm - how does this occur?

A

variable complement fixation, + DAT for IgG as it binds to Rh, is removed by macrophages and sequested in spleen

97
Q

Autoimmune hemolytic anemia - warm tx

A

supportive - manage underlying

GC, rituximab
second line is things heme gives IVIG< plex

and surgery for splenectomy

98
Q

Autoimmune hemolytic anemia - cold - who is this seen in?

A

old men

99
Q

Autoimmune hemolytic anemia - cold - how does this occur?

A

IgM complement fixation which react with surface ag at low temps and cause either intra or extra vascular hemolysis upon rewarming

100
Q

Autoimmune hemolytic anemia - cold - 3 common diseases?

A

ebb
mycoplasma
lymphoma

101
Q

Autoimmune hemolytic anemia - cold - DAT ?

A

+

102
Q

Autoimmune hemolytic anemia - cold - tx

A

supportive with folate and vit b12 if defic
avoid trigger
underlying disease tx

103
Q

Autoimmune hemolytic anemia - cold - complication?

A

thrombosis - may consider thromboprophylaxis with acute exacerbations or for chronic disease in high risk situations

104
Q

Extrinsic cause of hemolysis: how does microangiopathic hemolytic anemia occur?

A

microcirculatory fragments by threads of fibrin deposited in arterioles

105
Q

microangiopathic hemolytic anemia - underlying disease- list 6

A

malign htn
preeclampsia
vasculitis
ttp
purpura
dic
vascular anomalites

106
Q

Extrinsic cause of hemolysis: Cardiac - how does this occur?

A

shearing from turbulance - ie valves, av fistula, AS, LS heart lesion

107
Q

Extrinsic cause of hemolysis: march hemoglobinemia

A

breaking IV rbc by repetitive pounding - soldiers and marathoners

108
Q

What are environmental/toxin causes of hemolysis? List 7

A

burns
freshwater drown
hyperthermia
brown recluse spider
venomous snake bite
castor beans
mushrooms
malaria
bartonella
clostridium

109
Q

What is a DAT test for ?

A

hemolytic anemia - detects abodies or complement on human rbc membranes by adding a reagant that detects igG, A M or complement

110
Q

How to temporize/slow hemolysis - drug?

A

prednisone 1mg/kg

111
Q

What is sickle cell disease?

A

AR mutation producing HbS as a mutation in he beta globin gene

112
Q

In sickle cell, what happens to rbc when exposed to deoxygenation or various stressors?

A

rbc sickles, rigid so that blood becomes sludge, undergoes sequestration in liver and spleen

113
Q

Sickle cell disease: complications list 6

A

vaso occlusive events
chronic hemolysis
thrombosis
organ injury - renal papillary necorsis, splenic infarct, PE, traumatic hyphema, exertional rhabdo, sudden cardiac death

114
Q

Sickle cell disease: when to consider life threatening aplastic crisis?

A

hbg <20 after previously stable and retic count <2% -

*can occur after suppression epoesis infection or folate defici

115
Q

Sickle cell disease: Acute vaso occlusive event: precip factors?

A

antecedent infection
cold exposure
stress/trauma

116
Q

Painful Sickle cell disease crisis - what happens?

A

origin in tissue ischemia which leads to irev sickling, more sludge and obstruction

117
Q

Painful Sickle cell disease crisis which body parts typically involved?

A

abdo
chest
back
extremities

118
Q

Sickle cell disease neuro diseases?

A

tia
cerebral infarct
ich
scinfarct
vestibular
hearing issue

119
Q

What is an acute chest syndrome?

A

SCD: fever cough hypoxia, chest pain, sob and new infiltrate on cxr

look for mycoplasma/chlam infection

120
Q

When does autoinfarction of spleen occur in kids with sickle cell?

A

10-27mo

121
Q

Functional asplenia in sickle cells kiddos: 1mo-5y how to tx?

A

amox/pen

122
Q

What bugs are people with scd more at risk for getting?

A

encapsulated organisms
salmonella om!!

123
Q

Treating a sickle cell patient - important considerations:

A
  1. hydroxyurea: induces HbgF, reduces pain crisis and need blood transfusion
  2. transfusion for severe exacerbation with evidence of hypoxia/hypoperfusion, acute organ damage, preop
  3. exchange transfusion if acute chest syndrome, stroke, asplastic crisis, acute splenic sequestration
  4. stem cell transplant: cure!!
124
Q

Acute pain crisis tx

A

analgesia
nsaids
ivf

125
Q

Stroke in SCD pt:

A

exchange transfusion with goal hbs <30% and hbg of 10

tpa in adults also consideration

126
Q

Acute chest syndrome management of scd:

A

hydration
analgesia
oxygenate/ventil
CTX and azithromycin

exchange transf if multilobe involvemnt or worsening hypoxemia, neuro abn, multi organ involvement

127
Q

What GU concern is more common in SCD?

A

priapism - aspirate blood and irrigate with alpha adrenergic agent

128
Q

What are the symptoms of polycythemia?

A

mild headache
vertigo/dizzy, blurry vision due to vol oload

hyperviscosity: thrombosis, plt dysfunc (epistaxis, spont bruising, GIB)

129
Q

What are the signs of polycythemia?

A

plethoric skin/mm
optic fundal venous congestions
splenomegaly
hf

130
Q

Causes of absolute erythrocytosis: list 8

A

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

131
Q

Causes of absolute erythrocytosis: list 5

A

emesis, diarrhea, diuretics, burns, low albumin

chronic plasma contraction: hypoxia, hypertension, tobacco or etoh use

132
Q

What is primary polycythemia vera?

A

chronic myeloprolif disorder caused by JAK2mutation

133
Q

polycythemia vera: symptoms

A

h/a
weak
dizzy
excess sweat
plethora
pruritis after hot water exposure

134
Q

polycythemia vera list 3 complications of disease

A

cva, mi, dvt
bleeding
risk leukemic or fibrotic transformation

135
Q

Labs: polycythemia vera

A

all cell lines involved and typically big with elevated hbg, rbc mass, plt and wbc big

136
Q

polycythemia vera diagnostic criteria

A

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

137
Q

polycythemia vera tx

A
  1. phlem to hct <45%
  2. daily aspirin 40-100mg po for primary prevention thrombosis
  3. high risk (hx thrombosis, age >60: hydroxyurea 500mg po bid
138
Q

Secondary polycythemia: defn?

A

appropr epo response to abn tissue oxygen levels (ie excluded by N art o2 sat)

139
Q

Secondary polycythemia: emergent tx

A

phlebotomy - 500ml and replace with saline same

true emerg = 1-1.5L of blood over 24 hour period

Rosens (48 decks)

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