Transcript Anemia Dell Children’s Medical Center April 12, 2014

Anemia
Dell Children’s Medical Center
April 12, 2014
Virginia Harrod, MD, PhD
Pediatric Hematology Oncology
Overview
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Definition of anemia
Review of CBC values
Review of Hemoglobin
Types of Anemia
– Microcytic, macrocytic, normocytic
• Diagnostic Evaluations and Workup
• When to consult or refer to Hematology
Definition of Anemia
• a condition in which the blood is deficient in
red blood cells, in hemoglobin, or in total
volume
http://www.merriam-webster.com/dictionary/anemia
What is in a CBC?
• WBC (white blood cell)
– Differential (neutr, lymphs, monos, eos, baso)
• Hemoglobin (RBC, Hct, MCV, MCHC)
• Platelets (MPV)
What is missing from a CBC?
• Reticulocyte count
– Gives an indication if the body “knows” something
is wrong and if it can respond appropriately
• Peripheral smear
– Gives us insight into processes
Definition of Anemia
Age (years)
Hemoglobin (g/dL)
Mean (low limit)
Hematocrit (%)
Mean (low limit)
0.5-1.9
12.5 (11.0)
37 (33)
2-4
12.5 (11.0)
38 (34)
5-7
13.0 (11.5)
39 (35)
8-11
13.5 (12)
40 (36)
12-14
Female
Male
13.5 (12.0)
14.0 (12.5)
41 (36)
43 (37)
15-17
Female
Male
14.0 (12.0)
15.0 (13.0)
41 (36)
46 (38)
18-49
Female
Male
14.0 (12.0)
16.0 (14.0)
42 (37)
47 (40)
Nathan and Oski’s Hematology of Infancy and Childhood 6th Ed., Ch10, pp409
Hemoglobin
• Structure
• Synthesis
• Function
http://themedicalbiochemistrypage.org/hemoglobin-myoglobin.php
Hemoglobin
• Structure
• Synthesis
• Function
• a2b2
http://sickle.bwh.harvard.edu/hbsynthesis.html
Hemoglobin
• Structure
• Synthesis
• Function
– Carry oxygen from lungs to body and carry CO2
from body to lungs
– Found in Red Blood Cells
• 97% of the RBC is hemoglobin
en.wikipedia.org
American Society of Hematology Image Bank Online
Classifications of Anemia
• Based on RBC size (MCV)
– Microcytic (hypochromic)
– Macrocytic
– Normocytic (normochromic)
• Based on Physiology
– Production problem
– Maturation problem
– Destruction problem
Macrocytic Anemias
• Megaloblastic marrow changes
– Vitamin B12 deficiency
– Folic acid deficiency
– Hereditary oroticaciduria
• Without megaloblastic changes
– Liver disease
– Hypothyroid
– Bone marrow failure
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Aplastic anemia
Fanconi’s anemia
Diamond Blackfan anemia
Myelodysplasia
Macrocytic Anemias
• Megaloblastic marrow changes
– Vitamin B12 deficiency
• Usually associated with pernicious anemia
– Loss of gastric parietal cells/intrinsic factor required for
absorption of vit B12 in ileum.
• Otherwise rare except some at risk groups:
– Lower socioeconomic group, infants, elderly
– Folic acid deficiency
– Hereditary oroticaciduria
Macrocytic Anemias
• Megaloblastic marrow changes
– Vitamin B12 deficiency
– Folic acid deficiency
• Natural food sources
– Dark green leafy veggies, fruit, nuts, beans, dairy, liver
– 01/1998 – US Government (FDA) – requiring supplementation
» Breads, cereals, pastas, rice, grains
• Uncommon (poor diet, alcoholism, malabsorptive d/o)
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Am J Clin Nutr. 2013 Oct;98(4):1042-7. doi: 10.3945/ajcn.113.059683. Epub 2013 Aug 14.
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Near-elimination of folate-deficiency anemia by mandatory folic acid fortification in older
US adults: Reasons for Geographic and Racial Differences in Stroke study 2003-2007.
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Odewole OA1, Williamson RS, Zakai NA, Berry RJ, Judd SE, Qi YP, Adedinsewo DA, Oakley GP Jr.
Macrocytic Anemias
• Megaloblastic marrow changes
– Vitamin B12 deficiency
– Folic acid deficiency
– Hereditary oroticaciduria
• Without megaloblastic changes
– Liver disease
– Hypothyroid
– Bone marrow failure
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Aplastic anemia
Fanconi’s anemia
Diamond Blackfan anemia
Myelodysplasia
Bone Marrow Failure
– Fanconi’s anemia
Characteristics
Smaller than average
Usually presents before teen years
Developmental defects (60%): thumb/arm
Developmental delays
GI disturbances
– Diamond Blackfan anemia
– Aplastic anemia
– Myelodysplasia
http://radiopaedia.org/articles/fanconi-anaemia
Bone Marrow Failure
– Fanconi’s anemia
– Diamond Blackfan anemia
Characteristics
Craniofacial malformations
Usually presents in infancy
Developmental defects (60%): thumb/arm
Cardiac, GU malformations
Low birth weight, growth delays
– Aplastic anemia
– Myelodysplasia
http://dbafoundation.org/testimonials/
DBA Foundation Support
Bone Marrow Failure
– Fanconi’s anemia
– Diamond Blackfan anemia
Characteristics
– Aplastic anemia
Present similar to leukemia
– Myelodysplasia
Pancytopenia: fever, bruising, preceding illnesses
Normal Marrow
MDS
Aplastic Anemia
ASH Image Bank Online
Microcytic Anemias
• Usually represents impaired synthesis
– Heme
• Assembly line is interrupted
• Iron
• Lead
– Globin
• Thalassemias
Iron Absorption
New Human Physiology, 2nd Ed., Paulev and Zubieta, 2004
Iron Absorption
New Human Physiology, 2nd Ed., Paulev and Zubieta, 2004
Iron Absorption
Calcium ?
New Human Physiology, 2nd Ed., Paulev and Zubieta, 2004
Iron Absorption
Calcium ?
Lead tox
New Human Physiology, 2nd Ed., Paulev and Zubieta, 2004
Iron Deficiency Anemia
• Low MCV
• Low Retic
• Low ferritin
• Common clinical scenarios:
– Pale child, high milk intake, “picky eater”, clinically
appears well (not fatigued, no fevers, etc)
Microcytic Anemias
• Usually represents impaired synthesis
– Heme
• Iron
• Lead
– Globin
• Thalassemias
ASH Image Bank Online
Thalassemia
• Alpha
– Decreased production of alpha globin chains
• Beta
– Decreased production of beta globin chains
– Beta major (b0), beta intermedia (b+)
• Typically autosomal recessive, but some not
Microcytic Anemias
• Usually represents impaired synthesis
– Heme
• Iron
• Lead
– Globin
• Thalassemias
– Basophilic
stippling
ASH Image Bank Online
Microcytic Anemias
• Usually represents impaired synthesis
– Heme
• Iron
• Lead
– Globin
• Thalassemias
ASH Image Bank Online
Microcytic Anemia Workup
Mentzer Index
Not reliable
Just measure ferritin
http://www.aafp.org/afp/2009/0815/p339.html
Normocytic anemias
• Hemolysis (destruction)
– External factor mediated
• Antibodiy mediated, microangiomathic, toxins, infectious,
hypersplenism
– Membrane disorders of RBC
• Spherocytosis, elipotocytosis, PNH (paroxysmal nocturnal
hemoglobinuria)
– Hemoglobinopathies (sickle cell disease)
• Hb S, Hb C
– Enzyme disorders
• G6PD, PK def
– Hemorrhage
– Some production disorders:
• Red cell aplasia, TEC, marrow replacement (leukemia)
Antibody Mediated
• Auto-immune hemolytic anemia (AIHA)
– Idiopathic or possibly infection, drugs, etc
– Warm and Cold antibodies
– Diagnostic indicators:
• Direct coombs
• Reticulocyte counts
• Microangiopathic/infectious
Membrane Disorders
• Spherocytosis
– Defect in spectrin
– Autosomal Dominant
– Often present with “newborn jaundice” (first day
of life)
– Family history of splenectomies
Membrane Disorders
ASH Image Bank Online
Sickle Cell Anemia
• Substitution on 6th position beta chain (val for
glutamic acid)
• Hemoglobin forms long polymers under
deoxygenated (hypoxic) states
• Shortened RBC life span
• Microvascular obstruction/ischemia/infarction
• 10% African Americans carry trait, other
populations too
Sickle Cell Anemia
• Life threatening concerns
– Splenic sequestration
– Infection (encapsulated organisms, functional
asplenia)
• Other concerns
– Aplastic crisis (parvo)
– Vaso-occlusive episodes (acute chest)
Sickle Cell Anemia
http://en.wikipedia.org/wiki/Sickle-cell_disease
ASH online image bank
Anemia Workup Algorithm
Janus, et al., Evaluation of Anemia in Children, Am Fam Physician 2010 Jun 15; 81(12): 1462-1471
Treatments
• All anemias
– Fix the problem
• Deficiencies – give iron, vitamin, etc
– Sickle cell/thal
• Control symptoms
• Hydroxyurea
• Transfusions
– Destruction issues
• Splenectomy, treat infection
– Marrow failure/leukemia
• Immune suppression, chemotherapy, marrow transplant
Consult Heme?
• All “genetic” conditions
• Iron deficiency anemia that doesn’t ‘get
better’
• Anemia resulting in transfusion or
hospitalization
• Phone consults are welcome for quick review
and ‘next step’ thoughts
In Review
•
•
•
•
Definition of anemia
Review of CBC values
Review of Hemoglobin
Types of Anemia
– Microcytic, macrocytic, normocytic
• Diagnostic Evaluations and Workup
• When to consult or refer to Hematology