Anemia Flashcards
Case
CC: pallor
J.O.M 9/F , sees you for the first time with the chief complaint of
pallor
HPI: 4 week history of easy fatiguability, exertional dyspnea,
lethargy
2 week history of pallor with note of icteric sclerae
ROS:
(-) fever
(-) wt loss
(-) rashes
(-) easy bruisability
(-) epistaxis
(-) bone pain
(-) gum bleeding
(-) melena/ hematochezia
(-) tea colored urine
PMHX: multiple histories of blood transfusion
FMHx: (+) blood dyscracia
PE: BP 100/50 HR 140 RR 28 Temp 37
(+) generalized pallor, Weight for age below -3 , Length for age
below -3
(+) slightly icteric sclera, pale conjunctiva (+) maxillary hyperplasia
(+) frontal bossing
(+) dynamic precordium (+) grade 3/6 systolic murmur, apex
displaced at 6th ICS LAAL
Distended abdomen with (+) hepatosplenomegaly
Pale nailbeds, (+) bipedal edema
Tanner of Breast - 1; Tanner of Pubic Hair - 1
Laboratory
CBC:
Hgb 5.0 (LOW) 12.0- 15.0 g/dL
Hct 18 (LOW) 36 – 48%
RBC 7 (HIGH) 3.5 – 5.5 ml/UL
MCV 65 (LOW) 80-100 FL
MCH 18 (LOW) 25-35 PG
RDW 12 11 – 16 FL
WBC 9.0 4.5 -11.0 K/UL
Segmenters 60 40-74
Lymphocytes 25 14-46
Monocytes 10 4-13
Platelet Count 350 150 – 450 K/UL
PBS: marked hypochromasia and microcytosis, nucleated RBCs
CXR: cardiomegaly with increased vascular markings
2D echo: dilated cardiomyopathy with poor contractility
Iron Studies:
Values Normal Values
Serum Iron 300 (HIGH)
Normal: 26 – 160 g/dL (females)
Transferrin
Normal: 250 204 - 360 g/dL
Ferritin 1350 (HIGH)
Normal: 12-160 ng/ml (females)
Hgb Electrophoresis:
Lanes 5 and 6: No Hb A or A2 is present, Hb F is 100%
What is the primary working impression?
I. Primary Working Impression:
Beta – Thalassemia Major/ Cooley Anemia
Basis:
o History:
o Fatigue
o Exertional Dyspnea/ Shortness of breath
o Pallor
o Multiple blood transfusions in the past – patients
require BT starting at 2 mos – 2yrs but rarely later
o Family member with similar illness – autosomal
recessive inheritance
o Possible complications: cardiac, endo
PE:
o Wide pulse pressure
o Tachycardic
o Generalized pallor
o Failure to thrive and short stature
o Typical facies (maxillary hyperplasia/ dental
malocclusion, flat nasal bridge, frontal bossing)
o Hepatosplenomegaly
o Complications: Cardiac dilated cardiomyopathy
What are the differentials?
- IRON DEFICIENCY ANEMIA
Rule in
-Anemia (signs and symptoms)
-Pallor, tachycardic, failure to
thrive
Rule out
-Not a genetic disease
-Unlikely to have hx of multiple
BT
-Will not have the typical facies
of thalassemia
-Unlikely to present with
hepatosplenomegaly
-Hgb Electrophoresis: clinches
the diagnosis
IDA vs Thalassemia
IDA
MCV low
MCH low
serum iron low
transferrin/TIBC increased
ferritin low
RBC low
RDW increased
Thalassemia
MCV low
MCH low
serum iron HIGH
transferrin/TIBC LOW
ferritin HIGH
RBC INCREASED
RDW N or LOW
- ANEMIA OF CHRONIC DISEASE
Rule in
Anemia (signs and symptoms)
Pallor, tachycardic, failure to
thrive
Rule out
Other signs and symptoms of
chronic illness (Infection: TB,
Osteomyelitis, bronchiectasis;
Renal: CKD, Rheumatologic:
SLE, RA, IBD)
Not a genetic disease
Unlikely to have hx of multiple BT
Will not have the typical facies
of thalassemia
Unlikely to present with
hepatosplenomegaly
Hgb Electrophoresis: clinches
the diagnosis
- LEAD TOXICITY
Rule in:
Anemia (signs and symptoms)
Pallor, tachycardic, failure to
thrive
Rule out:
Lacking in history of
significant lead exposure (old
house, gasoline station) to
suspect the diagnosis
Stigmata of Lead Toxicity: GI
symptoms (anorexia,
vomting, constipation,
abdominal pain, lead lines),
Neurobehavioral symptoms
(inattentiveness, impaired
cognition, learning problems,
weakness, peripheral palsies)
Not a genetic disease
Unlikely to have hx of multiple
BT
Will not have the typical facies
of thalassemia
Unlikely to present with
hepatosplenomegaly
Hgb Electrophoresis: clinches
the diagnosis
- SIDEROBLASTIC ANEMIA
Rule in
-Anemia (signs and symptoms)
-Pallor, tachycardic, failure to
thrive
-If congenital : may present
with hepatosplenomegaly
and multiple histories of BT
Rule out:
-genetic disease – X-linked
(congenital)
-Will not have the typical facies
of thalassemia
-Hgb Electrophoresis: clinches
the diagnosis
Difference between Thalassemia and Anemia of Chronic Disease
Thalassemia
MCV low
MCH low
serum iron HIGH
transferrin/TIBC low
ferritin HIGH
RBC Increased
RDW N or Low
Anemia of Chronic Disease
MCV N
MCH N
Serum iron Low
Transferrin/TIBC low
ferritin increased
Thalassemia vs lead toxicity
Thalassemia
MCV low
MCH low
serum iron HIGH
transferrin/TIBC low
ferritin HIGH
RBC Increased
RDW N or Low
Lead toxicity
MCV low
MCH low
*** basophilic stippling
Thalassemia vs Sideroblastic anemia
Thalassemia
MCV low
MCH low
serum iron HIGH
transferrin/TIBC low
ferritin HIGH
RBC Increased
RDW N or Low
Sideroblastic anemia
MCV low
MCH low
serum iron Increased
transferrin/TIBC Increased
ferritin HIGH
RBC Increased
RDW extremely high
***ringed sideroblast
Diagnostics
Blood Typing
CBC with pc with retic count
PBS
Hgb Electrophoresis
Additional Labs to monitor long standing complications -
Hemosiderosis
Complications
- Cardio
Dilated Cardiomypathy,
Congested Heart Failure, Cardiac
Arrythmias
2D echo, CXR,
ECG
- Endo hypothyroidism,
gonadal failure, hypoparathyroidism,
and diabetes mellitus
TSH, fT4, T3
LH, FSH
FBS, UA
PTH, Ca, Phos
Treatment
Treatment:
Transfusion therapy promotes general health and well-being and
avoids the consequences of ineffective erythropoiesis. A
transfusion program generally requires monthly transfusions, with
the pretransfusion hemoglobin level >9.5 and <10.5 g/dL.
In patients with cardiac disease, higher pretransfusion
hemoglobin levels may be beneficial.
Bone marrow transplantation has cured >1,000 patients who have
thalassemia major. Most success has been in children younger
than 15 yr of age without excessive iron stores and hepatomegaly
who have HLA-matched siblings. All children who have an HLAmatched
sibling should be offered the option of bone marrow
transplantation.
Splenectomy is the principal surgical procedure used for many
patients with thalassemia.
Conversely, splenectomy is justified
when the spleen becomes hyperactive, leading to excessive
destruction of RBCs and thus increasing the need for frequent
blood transfusions, resulting in more iron accumulation. Several
criteria are used to aid in the decision for splenectomy; a practical
one suggests that splenectomy may be beneficial in patients who
require more than 200-250 mL/kg of PRBC per year to maintain an
Hb level of 10 g/dL.
Diet: A normal diet is recommended, with emphasis on the following supplements: folic acid, small doses of ascorbic acid
(vitamin C), and alpha-tocopherol (vitamin E). Iron should not be
given, and foods rich in iron should be avoided.
Complications:
Transfusional hemosiderosis can be prevented by the use of
deferoxamine (Desferal). Deferoxamine is given subcutaneously
over 10–12 hr, 5–6 days a week. Side effects include ototoxicity
with high-frequency hearing loss, retinal changes, and bone
dysplasia with truncal shortening. Deferiprone is a new iron
chelator approved by the U.S. Food and Drug Administration for
children >2 yr
PLEASE READ p.185 table
RULE OF THUMB
Rule of thumb:
To determine lower limit of N for Hgb concentration:
- “The Eleven Plus One Rule”
- 11 + 0.1 x (age in yrs) = lower limit of N Hgb conc
To determine the lower limit of N for MCV:
- “The Seventy Plus One Rule”
- 70 + 1 x (age in yrs) = lower limit of N MCV
To determine the upper limit of N for MCV:
- 84 + 0.6 x (age in yrs) = upper limit of N MCV (until UL of 96)
Retic ct (% of circulating RBCs) NV = 0.5-1.5%: reflects rate of RBC
production sec to hemolysis or impaired BM function
What is IRON DEFICIENCY ANEMIA?
455: IRON DEFICIENCY ANEMIA (IDA)
- MC nutritional deficiency in children
Patho
- Insufficient total body iron to maintain normal
physiologic functions
- Imbalance of equilibrium between absorption and
excretion of iron
3 stages of high iron demand:
- Infants: most at risk; extremely rare during 1st 4-6 MOL
o Milk products (incl breastmilk) have low
iron stores
§ Depleted at 6mos so need iron
supp
- Toddler: Common cause in 1-3yo
- Adolescents – growth spurts, poor eating practices,
menstruation, pregnancies
Risk factors for IDA
infants and toddlers:
LBW
prematurity
perinatal blood loss
early cord clamping
excessive consumption of cow’s milk
Older children and adolescents:
Increased requirements (growth spurt, pregnancy)
Occult chronic blood loss (peptic ulcer; polyp, hemangioma)
menstrual blood loss
infection with intestinal hookworm, Trichuris, Plasmodium, Helicobacter pylori, Giardia lamblia
Excessive cow’s milk – chronic low grade hemorrhagic
enteropathy, low iron content, poor bioavailability of iron (50% in BM, 5-10% in MF), prevention of eating
iron-rich foods
- Lead poisoning, vegan/poor meat intake
- As iron stores become depleted: inc RDW –> dec serum
ferritin –> dec MCV –> dec Hgb
What are the clinical manifestations of IDA?
CM
1. Asx’c – most with mild to mod anemia
2. Hgb 6-10 g/dl – mild irritability
Hgb 7-8 g/dl – pallor: most impt clinical sign (palmar:
most sn)
Hgb <5 g/dl – lethargy, anorexia, easy fatigability,
systolic flow murmurs, high-output HF
3. Koilonychia – spoon nails
4. Pica – desire to eat nonnutritive substances
5. Pagophagia – desire to ingest rice
6. Irreversible neurocognitive effects
What are the diagnostics?
Dx
1. CBC – low RBC, MCV, MCHC; inc RDW; variable plt
(thrombosis if severe)
2. Low reticulocyte count (due to low substrate iron)
3. PBS – microcytic, hypochromic RBCs: due to dec Hgb
production or faulty function, polychromasia,
anisopoikilocytosis
4. Low serum iron (iron studies not required)
5. Low serum ferritin – earliest sign
6. High TIBC, transferrin, free erythrocyte protoporphyrin
Ferritin = blood iron stores
Transferrin, TIBC – transport iron in blood
Mnemonics for MICROCYTIC ANEMIA
Mnemonic for microcytic anemia: “TAILS”
Thalassemia
Anemia of inflammation
Iron deficiency anemia
Lead poisoning
Sideroblastic anemia
What is the management of IDA?
Mgt
1. Look for cause of IDA and address underlying problem
a. Control/evaluate for blood loss
- Dietary counselling if anemia due to nutritional cause
a. Delay introduction of cow’s milk until at least 1 yo
b. Limit intake of cow’s milk to 16-24 oz/d
c. Promote iron rich foods (red meat
(beef/lamb), liver, kidney, oily fish
(pilchards, sardines) - Iron supplementation/iron therapeutic trial – iron salts
3-6mkd of elemental iron OD-TID x 3-4 mos
a. Ferrous sulfate: 20% elemental iron
§ GI SE (constipation), staining of
teeth, palatability, metallic taste
§ Give prior to eating. Take with
juice/meat to enhance
absorption (Not milk)
b. Ferrous fumarate: 33% elemental iron
§ More acceptable taste,
expensive
c. Ferrous gluconate: 12% elemental iron
- Iron polymaltose complex causes less GI upset
- Continue tx for 2-3 mos after Hgb has normalized (to
replete hepatic stores)
- 6-12 mos at risk of developing IDA
- Adolescent females, children from LIC, fad dieters
- MV with iron is inadeq - Blood transfusion – for pxs with imminent HF or severe
anemia with ongoing blood loss, Hgb <7mg/dl - F/U – repeat CBC 4 weeks after iron tx
o Hgb should have risen by at least 1-2 g/dl,
often within N levels
- If severe: check for reticulocytosis within 2-3d of tx
- If poor response: consider other causes of anemia
- Retic count should inc in 4-6d
- WOF long term neurocognitive deficits
Expected response to iron therapy
12-24hrs: subjective improvement (increased appetite, decreased irritability)
26-48hrs: initial BM response (erythroid hyperplasia)
48-72hrs: reticulocytosis, which peaks at 507 days
4-30 days: increase Hgb levels
1-3 months: repletion of iron stores
What is thalassemia?
- Disorder wherein the alpha and globin chains are
disrupted due to disease causing variant in one or
more globin genes - Impaired production of either the alpha or beta hgb
chain
Pathophysio of iron
pathophysio of iron overload in thalassemia
Pathophysio of iron overload
- Chronic hemolysis + repeated BT + increased GIT absorption lead to iron overload. This results in high oxidative stress, high levels of free radicals, low levels of anti-oxidants
Alpha Thalassemia vs Beta thalassemia
—–ALPHA THALASSEMIA—–
-caused by deletions in one or more gene encoding for alpha globin chain
-vary depending on numbers of gene deletion
Manifestations:
Hydrops fetalis with Bars Hgb
(4 Foci deleted) –> severe microcytic anemia
Thalassemia Major (HbH Disease) –> moderate microcytic anemia
Thalassemia minor (2 foci deleted) –>mild, microcytic anemia
Silent Carrier (1 foci deleted) –> normal Hgb, normal MCV
Diagnostics:
Definitive diagnosis through hemoglobin electrophoresis
CBC: anemia and low red cell indices with normal red cell distribution width; decreased reticulocyte count due to ineffective erythrophoresis
PBS: microcytic, hypochromic RBCs, target cells and Heinz bodies
Management:
*Hematopoietic stem cell transplantation is the only cure for 4 foci deletion and for beta thalassemia major
*Frequent transfusions, iron chelation therapy with DEFEROXAMINE or DEFERASIROX as needed
* folate supplementation, low iron diet
*Splenectomy for those who develop hypersplenism (falling steady state Hgb with thrombocytopenia or rising transfusion requirements)
—–BETA THALASSEMIA—–
-caused by mutations in 1 or both of the beta globin chains
-severity correlates with the amount of B-globin production
Manifestations:
B-thalassemia Major (both beta globin genes mutated) –> severe microcytic anemia with target cells; transfusion dependent
B-thalassemia Intermedia (at least 1 beta globin genes mutated) –> moderate microcytic anemia; non-transfusion dependent
B-Thalassemia Minor/Trait (1 beta globin gene mutated) (carrier) –> mild, microcytic anemia
Diagnostics:
Definitive diagnosis through hemoglobin electrophoresis
CBC: anemia and low red cell indices with normal red cell distribution width; decreased reticulocyte count due to ineffective erythrophoresis
PBS: microcytic, hypochromic RBCs, target cells and Heinz bodies
Management:
*Hematopoietic stem cell transplantation is the only cure for 4 foci deletion and for beta thalassemia major
*Frequent transfusions, iron chelation therapy with DEFEROXAMINE or DEFERASIROX as needed
* folate supplementation, low iron diet
*Splenectomy for those who develop hypersplenism (falling steady state Hgb with thrombocytopenia or rising transfusion requirements)
Clinical manifestations
CM
“THAL”
Transfusion dependence
Hereditary – autosomal recessive
Anemia
Lifelong
1. Pallor, jaundice
2. Frontal Bossing, maxillary overgrowth, flat nasal bridge
3. Marked Hepatosplenomegaly
4. Bone deformities, pathologic fractures
5. Growth retardation/ failure (25-75%) – related to
nutritional deficiency (folate, Zn, vitamins D, selenium)
6. Need for repeated blood transfusions
Complications of multiple BT
- Iron depletion – most impt
- Cardiomyopathy, liver cirrhosis, DM, endocrine failure,
skin hyperpigmentation
Diagnostics of Thalassemia
Dx
1. CBC – mild to severe anemia with marked hypochromia
and microcytosis. Also of parents
2. PBS – abundant fragmented and target RBCs
3. Inc serum iron and ferritin
4. low reticulocyte ct
5. Hgb electrophoresis
- Beta thal = reduced/ absent HbA, elev HbA2, inc HbF
- Alpha thal = elev Hgb Barts
6. MRI T2, UTZ – hepatosplenomegaly, gallstones
7. Target organ monitoring – FBS, LFT, thyroid function
8. Bone scan
