Transcript Hemolytic Anemia

Hemolytic Anemia
Part I
FJ Albert, DO, DTM&H
Hospital Medicine
Lexington Medical Center
West Columbia, SC
Associate Professor
Clinical Internal Medicine
Edward Via College of Osteopathic Medicine
Carolinas Campus
Topic Summary
•
•
•
•
•
Anemia
Hemolytic Anemia
Hereditary Spherocytosis (HS)
Elliptocytosis
Paroxysmal Nocturnal Hemoglobinuria
(PNH)
• Pyruvate Kinase Deficiency
Topic Summary
• Glucose-6-Phosphate Dehydrogenase
Deficiency (G6PD)
• Thalassemias
• Sickle Cell Disease
• Disseminated Intravascular Coagulation
(DIC)
• Malaria
• Henoch-Schonlein Purpura (HSP)
Anemia
• Defined by hemoglobin value
• Hemoglobin <13.5 g/dL in women
• Hemoglobin <12 g/dL in men
Anemia
• Mean Corpuscular Volume (MCV)
– Size of a red blood cell
– Normal 80-100 fL
– Microcytic vs Macrocytic
• Mean Corpuscular Hemoglobin Concentration
(MCHC)
– Concentration of hemoglobin within a red blood cell
– Normal 32-36 g/dL
– Hypochromic vs Hyperchromic
Anemia Workup
•
•
•
•
Serum iron
Serum Total Iron Binding Capacity (TIBC)
Serum ferritin
Reticulocyte percentage/CBC smear
– Normal reticulocyte percentage 0.5-1.5%
Anemia Workup
• Iron deficiency anemia
– Low serum iron and high TIBC
– Low serum ferritin
• Anemia of chronic disease
– Low serum iron and low TIBC
– Normal or high serum ferritin
Hemolytic Anemia
• Elevated reticulocyte percentage
• Elevated serum LDH
• Elevated serum bilirubin (indirect
predominance)
• Low plasma haptoglobin
Haptoglobin
• RBC destruction releases hemoglobin in
plasma
• Free hemoglobin binds to haptoglobin
• Hemoglobin-haptoglobin complex
removed by liver
• Plasma haptoglobin, therefore, markedly
reduced with hemolytic anemia
Red Blood Cells
• Average survival is 110 to 120 days
• Two modes of destruction
– Increasing RBC age
– Hemolysis due to processes independent of
RBC age
Hereditary Spherocytosis
• Characterized by anemia, jaundice, and
splenomegaly
• Family history of hemolytic anemia
Hereditary Spherocytosis
• Alterations in genes that encode proteins
responsible for unifying RBC inner
membrane to the outer lipid bilayer
• Spectrin deficiency most common protein
deficiency seen in HS
• Passage of RBCs through spleen
progressive loss of RBC lipid layer
acquired spheroid shapeultimate RBC
hemolysis
Spherocytosis
• Complete Blood Count (CBC)
– Anemia
– Reticulocytosis
– Low Mean Corpuscular Volume (MCV)
– Increased Mean Corpuscular Hemoglobin
Concentration (MCHC)
– Increased Red Cell Distribution Width (RDW)
– Spherocytes seen on CBC smear
Spherocytosis
• Direct and Indirect Antiglobulin (Coombs)
serology is NEGATIVE with spherocytosis
• POSITIVE Direct and Indirect Antiglobulin
(Coombs) tests are associated with
autoimmune hemolytic anemias
Normal RBCs
Spherocytes
Spherocytes
• Presence of spherocytes seen in
– Hereditary Spherocytosis (HS)
– Glucose-6-phosphate deficiency (G6PD)
– Snake bites
– Sepsis secondary to Clostridium
– Microangiopathic hemolytic anemia
Confirming Diagnosis of
Hereditary Spherocytosis
• Serologic testing
– Eosin-5-maleimide binding test
– Acidified glycerol lysis time or the
cryohemolysis test (either one in combination
with the Eosin-5-maleimide binding test)
Hereditary Spherocytosis
Treatment
• RBC transfusions for symptomatic anemia
• Folic acid (1 mg/day orally), to support
erythropoiesis
• Consideration of splenectomy
– Eliminate hemolysis and anemia
• Early splenectomy reduces risk of bilirubin
gallstone formationreduces need for
cholecystectomy later in life
Splenectomy
• ALL patients who undergo splenectomy
(regardless of reason), are at increased
risk for infections/sepsis from
encapsulated bacteria
• Proper immunization and/or antibiotic
considerations for splenectomized patients
– Hemophilus Influenzae B
– Streptococcus Pneumoniae
– Neisseria Meningitidis
Elliptocytosis
• Also known as hereditary ovalocytosis
• Autosomal dominant transmission
• Inherited disorder of one or more red
blood cell membrane proteins
Elliptocytosis
• Spectrum of disease from asymptomatic
(most cases) to life-threatening
• Normal individuals have up to 5% elliptical
RBC forms
• Hereditary Elliptocytosis associated with
15-100% elliptical RBC forms
Elliptocytosis
• Diagnosed by peripheral smear
abnormalities and other specialized
laboratory tests and DNA testing
• Treatment
– Folic acid (1mg/day) orally
– Red blood cell transfusions
– Splenectomy for severe disease
Paroxysmal Nocturnal
Hemoglobinuria (PNH)
• Defect in the glycosylphosatidyl-inositol
(GPI) anchor of hemoglobin, due, in turn,
to a genetic abnormality (PIG-A gene)
• Clinical manifestations relate to
hematopoietic function abnormalities
Paroxysmal Nocturnal
Hemoglobinuria (PNH)
• Hemolytic anemia
– Especially after viral or bacterial infections
• Hypercoagulable state
– Venous thrombosis, especially hepatic or
other intraabdominal venous system
• Bone marrow hypoplasia/aplasia
• Progression to myelodysplastic syndrome
(MDS) or acute leukemia
Pyruvate Kinase Deficiency
• Most common congenital NON-
SPHEROCYTIC hemolytic anemia
• Autosomal recessive transmission
• Deficiency of erythrocyte Pyruvate Kinase
enzymehemolysis
• Mechanism of hemolysis not clear
Pyruvate Kinase Deficiency
• Severity of disease is highly variable
• Some have life-threatening, transfusion
requiring, hemolytic anemia from onset at
birth
• Some have fully compensated disease
with minimal hemolysis
Pyruvate Kinase Deficiency
• Intrauterine PRBC transfusions in affected
fetuses with severe anemia
• Phototherapy, in addition to possible PRBC
transfusions, for severe hyperbilirubinemia
during neonatal period
Pyruvate Kinase Deficiency
• Oral folic acid (1 mg/day) is common
• Splenectomy for severe disease
– Reduces symptoms
– Reduces frequency of PRBC transfusions
• Hematopoietic cell transplantation if no
benefit from splenectomy
Glucose-6-phosphate
dehydrogenase deficiency
(G6PD)
• Most common enzyme disorder of red
blood cells in humans
• X-linked transmission
• Mostly asymptomatic, except following
exposure to agents that cause hemolysis
G6PD Deficiency
• Glucose-6-phosphate dehydrogenase
catalyzes first step of the hexose
monophospate (HMP) shunt
• HMP shunt protects RBCs from oxidative
injury via NADPH production
• Enzyme deficiency results in RBC oxidative
injury
G6PD Deficiency
• List of more commonly used medications
to avoid with known G6PD deficiency
– Dapsone
– Nalidixic Acid
– Nitrofurantoin
– Primaquine
– Sulfamethoxazole (TMP-SMX; Bactrim/Septra)
G6PD Deficiency
• Foods notorious for hemolysis in
G6PD deficiency
– Fava beans
• Others that MAY cause hemolysis
with G6PD deficiency (individualized
based on mutations)
– Red wine, legumes, blueberries, tonic
water
– Henna (tattoo ink)
Fear the Fava!
Thalassemia
• The major hemoglobin in NORMAL adults
is hemoglobin A, consisting of one pair of
alpha globin chains and one pair of beta
globin chains
Thalassemia
• Thalassemia refers to a spectrum of
diseases characterized by reduced or
absent production of these pairs of alpha
or beta globin chains
• Definitive diagnosis of ALL thalassemias is
by hemoglobin electrophoresis
• Microcytic, hypochromic anemia
– Low MCV and low MCHC, respectively
Beta Thalassemia
• Beta thalassemia is due to impaired
production of beta globin chains
• Associated with relative excess of alpha
globin chains
Beta Thalassemia
• Beta thalassemia minor
– Majority are asymptomatic
– Ninety percent of hemoglobin is Hgb A
• Beta thalassemia intermedia
• Beta thalassemia major
– Absent or markedly reduced beta chains
– Hemoglobin A absent or markedly reduced
– Only hemoglobin F and A2 present
– Severe hemolytic anemia
Alpha Thalassemia
• Alpha thalassemia is due impaired
production of alpha globin chains
• Associated with relative excess of beta
globin chains
Alpha Thalassemia
• A normal individual possesses four
functional alpha globin genes
• Alpha thalassemia reflects a loss of one,
two, three, or four of these genes
Alpha Thalassemia
• Alpha thalassemia minima
– Three normal alpha globin chain genes
– Asymptomatic, with normal blood counts
• Alpha thalassemia trait
– Two normal alpha globin chain genes
– Mild anemia (microcytic, hypochromic)
Alpha Thalassemia
• Hemoglobin H disease
– One normal/functional alpha globin chain
gene
– Symptomatic at birth
– Neonatal jaundice and life long hemolytic
anemia
• Hydrops fetalis and hemoglobin Barts
– No inherited normal alpha globin chain genes
– Not compatible with extrauterine life
Sickle Cell Disease
• Homozygous for hemoglobin S (HbSS)
– Most severe form of disease
– Results from substitution of valine, for
glutamic acid, as the sixth amino acid of the
beta globin gene
Sickle Cell Disease
• Heterozygous for both hemoglobin S and
hemoglobin C (HbSC)
• Heterozygous for hemoglobin S (HbS)
– Sickle cell trait
– Asymptomatic
Sickle Cell Disease
• Clinical hallmarks of disease
– Vaso-occlusive processes (sickle cell pain
crisis)
– Red blood cell destruction via hemolysis
Sickle Cell Disease
• Exacerbations of disease usually occur
secondary to some type of physiologic
stressor
– Infection
– Volume depletion
– Emotional stress/sleep deprivation
Sickle Cell Disease
• Clinical manifestations of disease
– Anemia (hemolytic)
– Reticulocytosis (3-15 reticulocyte %)
– Unconjugated hyperbilirubinemia
– Elevated serum LDH
– Low serum haptoglobin
– Sickled RBCs on peripheral smear
– Howell-Jolly bodies on peripheral smear
• Reflects hyposplenia from splenic infarctions
Sickle Cell Anemia
Sickled RBCs and
Howell Jolly Bodies
Sickle Cell Disease Treatment
• Acute pain crisis treatment
– Determine possible source of infection
– Supplemental oxygenation
– IVF with hypotonic fluid (e.g. ½ NS) is
preferred
– Pain control (narcotics are first line)
Sickle Cell Disease
• Chronic disease management
– Folic acid (1mg/day) orally
– Hydroxyurea
– Multivitamin (MVI)
– Calcium with vitamin D supplementation
Sickle Cell Disease
• Chronic disease management
– Vaccination against encapsulated bacteria
(Streptococcus pneumoniae, Hemophilus
influenzae (HIB), and Neisseria meningitidis)
– Vaccination against Hepatitis B, seasonal
influenza, and H1NI influenza