RBC disorders Flashcards
What is Anemia
Reduction in circulating red blood cell (RBC) mass
Anemia generally presents with
Weakness, fatigue, and dyspnea 2. Pale conjunctiva and skin 3. Headache and light headedness 4. Angina, especially with preexisting coronary artery disease
Anemia labs
Anemia is defined as Hb < 13.5 g/dL in males and< 12.5 g/dL in females
normal Hb is 13.5-17.5 g/dL in males and 12.5-16.0 g/dL in females
MCV classification of anemia
anemia can be classified as microcytic
(MCV < 80 µm3), normocytic (MCV = 80-100 µm3), or macrocytic (MCV > 100 µm3).
Basic Principles of Microcytic Anemias
Anemia with MCV < 80 µm3
B. Microcytic anemias are due to decreased production of hemoglobin.
1. RBC progenitor cells in the bone marrow are large and normally divide multiple
times to produce smaller mature cells (MCV = 80-100 µm3). 2. Microcytosis is due to an “extra” division which occurs to maintain hemoglobin
concentration.
C. Hemoglobin is made of heme and glob in; heme is composed of iron and
protoporphyrin. A decrease in any of these components leads to microcytic anemia. D. Microcytic anemias include (1) iron deficiency anemia, (2) anemia of chronic
disease, (3) sideroblastic anemia, and (4) thalassemia.
Iron Deficiency Anemia lab measures
Serum iron-measure of iron in the blood
2. Total iron-binding capacity (TIBC) - measure of transferrin molecules in the
blood 3. % saturation - percentage of transferrin molecules that are bound by iron
(normal is 33%) 4. Serum ferritin - reflects iron stores in macrophages and the liver
Pathology of Iron Deficiency Anemia
Due to decreased levels of iron
1. ↓i ron →↓heme → ↓hemoglobin → m
icrocytic anemia
B. Most common type of anemia
1. Lack of iron is the most common nutritional deficiency in the world, affecting roughly 1/3 of world’s population.
Iron is consumed in heme (meat-derived) and non-heme (vegetable-derived) forms.
1. Absorption occurs in the duodenum. Enterocytes have heme and non-heme (DMT1) transporters; the heme form is more readily absorbed.
- Enterocytes transport iron across the cell membrane into blood via ferroportin.
- Transferrin transports iron in the blood and delivers it to liver and bone marrow macrophages for storage.
- Stored intracellular iron is bound to ferritin, which prevents iron from forming free radicals via the Fenton reaction.
Causes of Iron Deficiency Anemia
- Infants - breast-feeding (human milk is low in iron)
- Children-poor diet
- Adults (20-50 years) - peptic ulcer disease in males and menorrhagia or pregnancy in females
- Elderly - colon polyps/carcinoma in the Western world; hookworm
(Ancylostoma duodenale and Necator americanus) in the developing world - Other causes include malnutrition, malabsorption, and gastrectomy (acid aids than Fe 3+).iron absorption by
Stages of Iron deficiency
- Storage iron is depleted - ↓ferritin; ↑TIBC
- Serum iron is depleted - ↓serum iron; ↓% saturation
- Normocytic anemia - Bone marrow makes fewer, but normal-sized, RBCs.
- Microcytic, hypochromic anemia - Bone marrow makes smaller and fewer RBCs.
clinical features of iron deficiency anemia
Clinical features of iron deficiency include anemia, koilonychia, and pica
lab findings of iron deficiency anemia
- Microcytic, hypochromic RBCs with ↑red cell distribution width (RDW)
- ↓ferritin; ↑TIBC; ↓ serum iron; ↓% saturation
- ↑Free erythrocyte protoporphyrin (FEP)
Treatment for Iron deficiency anemia
Treatment involves supplemental iron (ferrous sulfate)
Plummer-Vinson syndrome
Plummer-Vinson syndrome is iron deficiency anemia with esophageal web and
atrophic glossitis; presents as anemia, dysphagia, and beefy-red tongue
Anemia of Chronic Disease
Anemia associated with chronic inflammation (e.g., endocarditis or autoimmune
conditions) or cancer; most common type of anemia in hospitalized patients
Pathology of iron deficiency anemia
Chronic disease results in production of acute phase reactants from the liver,
including hepcidin.
1. Hepcidin sequesters iron in storage sites by
(1) limiting iron transfer from
macrophages to erythroid precursors and
(2) suppressing erythropoietin (EPO) production; aim is to prevent bacteria from accessing iron, which is necessary for their survival.
decrease iron - decrease heme- decrease hemoglobin - microcytic
Lab findings of Anemia of Chronic Disease
↑ ferritin, TIBC, serum iron, and % saturation
2. ↑ Free erythrocyte protoporphyrin (FEP)
Treatment for Anemia of chronic disease
Treatment involves addressing the underlying cause.
Sideroblastic Anemia
Anemia due to defective protoporphyrin synthesis
1. protoporphyrin heme hemoglobin microcyt ic anemia
Protoporphyrin is synthesized via a series of reactions…
- Aminolevulinic acid synthetase (ALAS) converts succinyl CoA to
aminolevulinic acid (ALA) using vitamin B6 as a cofactor (rate-limiting step). - Aminolevulinic acid dehydratase (ALAD) converts ALA to porphobilinogen.
- Additional reactions convert porphobilinogen to protoporphyrin.
- Ferrochelatase attaches protoporphyrin to iron to make heme (final reaction; occurs in the mitochondria)
What happens to iron in sideroblastic anemia
Iron is transferred to erythroid precursors and enters the mitochondria to form
heme. If protoporphyrin is deficient, iron remains trapped in mitochondria.
1. Iron-laden mitochondria form a ring around the nucleus of erythroid precursors;
these cells are called ringed sideroblasts (hence, the term sideroblastic anemia, Fig. 5.2).
congenital vs acquired sideroblastic anemia
Sideroblastic anemia can be congenital or acquired.
1. Congenital defect most commonly involves ALAS (rate-limiting enzyme).
- Acquired causes include
i. Alcoholism - mitochondrial poison ii. Lead poisoning - inhibits ALAD and ferrochelatase iii. Vitamin B6 deficiency - required cofactor for ALAS; most commonly seen as a side effect of isoniazid treatment for tuberculosis
lab findings for sideroblastic anemia
Laboratory findings include increased ferritin , decreased TIBC, increased serum iron, and increased % saturation
(iron-overloaded state).
Thalassemia
A. Anemia due to decreased synthesis o f the glob in chains of hemoglobin
1. ⬇️globin- ⬇️hemoglobin ➡️microcytic anemia
B. Inherited mutation; carriers are protected against Plasmodium falciparum malaria. C. Divided into - and -thalassemia based on decreased production of alpha or beta
globin chains.
1. Normal types of hemoglobin are HbF ( 2 2) , HbA ( 2 2) , and HbA 2 ( 2 2).
compare lab findings for microcytic anemias
a- thalassemia
α-Thalassemia is usually due to gene deletion; normally, 4 alpha genes are present on
1. One gene deleted - asymptomatic
chromosome 16
2. Two genes deleted - mild anemia with ↑ RBC count; cis deletion is associated
with an increased risk of severe thalassemia in offspring.
i. Cis deletion is when both deletions occur on the same chromosome; seen in
Asians ii. Trans deletion is when one deletion occurs on each chromosome; seen in
3. Three genes deleted-severe anemia; chains form tetramers (HbH) that
Africans, including African Americans E. -Thalassemia is usually due to gene mutations (point mutations in promoter or
4. Four genes deleted-lethal in utero (hydrops fetalis); chains form tetramers damage RBCs; Hb Barts is seen on electrophoresis
b-thalassemia
Thalassemia is usually due to gene mutations (point mutations in promoter or splicing sites ); seen in individuals of African and Mediterranean descent
1. Two β genes are present on chromosome 11; mutations result in absent (β0) or diminished (β+) production of the β-globin chain.
2. β-Thalassemia minor (β/β+) is the mildest form of disease and is usually asymptomatic with an increased RBC count.
i. Microcytic, hypochromic RBCs and target cells are seen on blood smear (Fig.
5.3). ii. Hemoglobin electrophoresis shows slightly decreased HbA with increased
HbA (5%, normal 25%) and HbF (2%, normal 1%).
.
b thalassemia major
β-Thalassemia major (β0/β0) is the most severe form of disease and presents with
severe anemia a few months after birth; high HbF (α2γ 2) at birth is temporarily
protective.
i. Unpaired α chains precipitate and damage RBC membrane, resulting
in ineffective erythropoiesis and extravascular hemolysis (removal of circulating RBCs by the spleen).
ii. Massive erythroid hyperplasia ensues resulting in (1) expansion of
hematopoiesis into the skull (reactive bone formation leads to ‘crewcut’ appearance on x-ray, Fig. 5.4) and facial bones (‘chipmunk fades’), (2) extramedullary hematopoiesis with hepatosplenomegaly, and (3) risk of aplastic crisis with parvovirus B19 infection of erythroid precursors.
iii. Chronic transfusions are often necessary; leads to risk for secondary
hemochromatosis v. Electrophoresis shows HbA2 and HbF with little or no HbA.
iv. Smear shows microcytic, hypochromic RBCs with target cells and nucleated
red blood cells.
Basic Principles of Macrocytic Anemia
A. Anemia with MCV > 100 µm3; most commonly due to folate or vitamin B12
deficiency (megaloblastic anemia)
B. Folate and vitamin B12 are necessary for synthesis of DNA precursors.
1. Folate circulates in the serum as methyltetrahydrofolate (methyl THF); removal
of the methyl group allows for participation in the synthesis of DNA precursors. 2. Methyl group is transferred to vitamin B12 (cobalamin). 3. Vitamin B12 then transfers it to homocysteine, producing methionine.
C. Lack of folate or vitamin B12 impairs synthesis of DNA precursors.
1. Impaired division and enlargement of RBC precursors leads to megaloblastic
anemia. 2. Impaired division of granulocytic precursors leads to hypersegmented
neutrophils. 3. Megaloblastic change is also seen in rapidly-dividing (e.g., intestinal) epithelial
cells.
D. Other causes of macrocytic anemia (without megaloblastic change) include
alcoholism, liver disease, and drugs (e.g., 5-FU).
Folate Deficiency and causes
Macrocytic
A. Dietary folate is obtained from green vegetables and some fruits.
1. Absorbed in the jejunum B. Folate deficiency develops within months, as body stores are minimal. C. Causes include poor diet (e.g., alcoholics and elderly), increased demand (e.g.,
pregnancy, cancer, and hemolytic anemia), and folate antagonists (e.g., methotrexate, which inhibits dihydrofolate reductase).
Folate deficiency lab findings
D. Clinical and laboratory findings include
1. Macrocytic RBCs and hypersegmented neutrophils (> 5 lobes, Fig. 5.5)
2. Glossitis
3. ↓ s erum folate
4. ↑ serum homocysteine (increases risk for thrombosis)
5. Normal methylmalonic acid
Most common cause of B12 deficiency
Pernicious anemia is the most common cause of vitamin B12 deficiency.
1. Autoimmune destruction of parietal cells (body of stomach) leads to intrinsic
factor deficiency
B12 deficiency pathology
A. Dietary vitamin B12 is complexed to animal-derived proteins.
1. Salivary gland enzymes (e.g., amylase) liberate vitamin B12, which is then bound
by R-binder (also from the salivary gland) and carried through the stomach.
2. Pancreatic proteases in the duodenum detach vitamin Bl2 from R-binder.
3. Vitamin Bl2 binds intrinsic factor (made by gastric parietal cells) in the small
bowel; the intrinsic factor-vitamin B12 complex is absorbed in the ileum.
B. Vitamin B12 deficiency is less common than folate deficiency and takes years to
develop due to large hepatic stores of vitamin B12.
Less common cause of B12 deficiency
Other causes of vitamin B12 deficiency include pancreatic insufficiency and damage
to the terminal ileum (e.g., Crohn disease or Diphyllobothrium latum [fish
tapeworm]); dietary deficiency is rare, except in vegans.
lab findings in B12 deficiency
E. Clinical and laboratory findings include
1. Macrocytic RBCs with hypersegmented neutrophils
2. Glossitis
3. Subacute combined degeneration of the spinal cord
i. Vitamin B12 is a cofactor for the conversion of methylmalonic acid to
succinyl CoA (important in fatty acid metabolism). ii. Vitamin B12 deficiency results in increased levels of methylmalonic acid,
which impairs spinal cord myelinization. iii. Damage results in poor proprioception and vibratory sensation (posterior
column) and spastic paresis (lateral corticospinal tract).
4. ↓ serum vitamin B12
5. ↑ serum homocysteine (s imilar to folate deficiency), which increases risk for thrombosis
6. ↑ methylmalonic acid (unlike folate deficiency)
Basic principles of normocytic anemia
A. Anemia with normal-sized RBCs (MCV = 80-100 µm3)
B. Due to increased peripheral destruction or underproduction
1. Reticulocyte count helps to distinguish between these two etiologies.
Reticulocytes
A. Young RBCs released from the bone marrow
1. Identified on blood smear as larger cells with bluish cytoplasm (due to residual
RNA, Fig. 5.6)
B. Normal reticulocyte count (RC) is 1-2%.
1. RBC lifespan is 120 days; each day roughly 1-2% of RBCs are removed from circulation and replaced by reticulocytes.
C. A properly functioning marrow responds to anemia by increasing the RC to > 3%.
D. RC, however, is falsely elevated in anemia.
1. RC is measured as percentage of total RBCs; decrease in total RBCs falsely elevates percentage of reticulocytes.
E. RC is corrected by multiplying reticulocyte count by Hct/45.
1. Corrected count > 3% indicates good marrow response and suggests peripheral
destruction. 2. Corrected count < 3% indicates poor marrow response and suggests
underproduction.
Extravascular hemolysis
B. Extravascular hemolysis involves RBC destruction by the reticuloendothelial system (macrophages of the spleen, liver, and lymph nodes).
Extravascular hemolysis pathology
- Macrophages consume RBCs and break down hemoglobin.
i. Globin is broken down into amino acids.
ii. Heme is broken down into iron and protoporphyrin; iron is recycled.
iii. Protoporphyrin is broken down into unconjugated bilirubin, which is bound
to serum albumin and delivered to the liver for conjugation and excretion
into bile.
lab findings for extravascular hemolysis
Clinical and laboratory findings include
i. Anemia with splenomegaly, jaundice due to unconjugated bilirubin, and
increased risk for bilirubin gallstones ii. Marrow hyperplasia with corrected reticulocyte count > 3%
Intravascular hemolysis clinical lab findings
Intravascular hemolysis involves destruction of RBCs within vessels.
1. Clinical and laboratory findings include
i. Hemoglobinemia ii. Hemoglobinuria iii. Hemosiderinuria - Renal tubular cells pick up some of the hemoglobin that
is filtered into the urine and break it down into iron, which accumulates as
hemosiderin; tubular cells are eventually shed resulting in hemosiderinuria. iv. Decreased serum haptoglobin
Hereditary spherocytosis
NORMOCYTIC ANEMIAS WITH PREDOMINANT EXTRAVASCULAR HEMOLYSIS
A. Inherited defect of RBC cytoskeleton-membrane tethering proteins
1. Most commonly involves ankyrin, spectrin, or band 3
B. Membrane blebs are formed and lost over time.
1. Loss of membrane renders cells round (spherocytes) instead of disc-shaped.
2. Spherocytes are less able to maneuver through splenic sinusoids and are consumed by splenic macrophages, resulting in anemia.
Hereditary spherocytosis lab findings
Clinical and laboratory findings include
1. Spherocytes with loss of central pallor (Fig. 5.7) 2. ↑ RDW and ↑ mean corpuscular hemoglobin concentration (MCHC) 3. Splenomegaly, jaundice with unconjugated bilirubin, and increased risk for
bilirubin gallstones (extravascular hemolysis) 4. Increased risk for aplastic crisis with parvovirus B19 infection of erythroid
precursors
D. Diagnosed by osmotic fragility test, which reveals increased spherocyte fragility in
hypotonic solution
Treatment hereditary spherocytosis
Treatment is splenectomy; anemia resolves, but spherocytes persist and Howell-Jolly bodies (fragments of nuclear material in RBCs) emerge on blood smear
Sickle Cell Anemia
NORMOCYTIC ANEMIAS WITH PREDOMINANT EXTRAVASCULAR HEMOLYSIS
A. Autosomal recessive mutation in β chain of hemoglobin; a single amino acid change replaces normal glutamic acid (hydrophilic) with valine (hydrophobic).
B. Gene is carried by 10% of individuals of African descent, likely due to protective role against falciparum malaria.
C. Sickle cell disease arises when two abnormal β genes are present; results in >90% HbS in RBCs
D. HbS polymerizes when deoxygenated; polymers aggregate into needle-like structures, resulting in sickle cells (Fig. 5.9).
l. Increased risk of sickling occurs with hypoxemia, dehydration, and acidosis.
2. HbF protects against sickling; high HbF at birth is protective for the first few months of life.
Treatment for sickle cell
Treatment with hydroxyurea increases levels of HbF
Pathology of membrane damage in sickle cell
E. Cells continuously sickle and de-sickle while passing through the microcirculation,
resulting in complications related to RBC membrane damage.
1. Extravascular hemolysis - Reticuloendothelial system removes RBCs with
damaged membranes, leading to anemia, jaundice with unconjugated hyperbilirubinemia, and increased risk for bilirubin gallstones.
2. Intravascular hemolysis - RBCs with damaged membranes dehydrate, leading to
hemolysis with decreased haptoglobin and target cells on blood smear. 3. Massive erythroid hyperplasia ensues resulting in
i. Expansion of hematopoiesis into the skull (‘crewcut’ appearance on x-ray) and
facial bones (‘chipmunk fades’) ii. Extramedullary hematopoiesis with hepatomegaly iii. Risk of aplastic crisis with parvovirus B19 infection of erythroid precursors
vaso-oclusive crisis in sickle cell
F. Extensive sickling leads to complications of vaso-occlusion.
1. Dactylitis - swollen hands and feet due to vaso-occlusive infarcts in bones;
common presenting sign in infants 2. Autosplenectomy - shrunken, fibrotic spleen. Consequences include
i. Increased risk of infection with encapsulated organisms such as Streptococcus
pneumoniae and Haemophilus influenzae (most common cause of death in children); affected children should be vaccinated by 5 years of age.
ii. Increased risk of Salmonella paratyphi osteomyelitis
iii. Howell-Jolly bodies on blood smear
3. Acute chest syndrome - vaso-occlusion in pulmonary microcirculation
4. Pain crisis 5. Renal papillary necrosis - results in gross hematuria and proteinuria
i. Presents with chest pain, shortness of breath, and lung infiltrates
ii. Often precipitated by pneumonia
iii. Most common cause of death in adult patients
clinical presentation of sickle cell
Sickle cell trait is the presence of one mutated and one normal chain; results in<
50% HbS in RBCs (HbA is slightly more efficiently produced than HbS)
1. Generally asymptomatic with no anemia; RBCs with < 50% HbS do not sickle in
vivo except in the renal medulla. i. Extreme hypoxia and hypertonicity of the medulla cause sickling, which
results in microinfarctions leading to microscopic hematuria and, eventually,
decreased ability to concentrate urine.
lab findings for sickle cell anemia
H!
H. Laboratory findings
1. Sickle cells and target cells are seen on blood smear in sickle cell disease, but not
in sickle cell trait.
2. Metabisulfite screen causes cells with any amount of HbS to sickle; positive in
both disease and trait
3. Hb electrophoresis confirms the presence and amount of HbS .
i. Disease - 90% HbS, 8% HbF, 2% HbA2 (no HbA)
ii. Trait - 55% HbA, 43% HbS, 2% HbA2
Hemoglobin C
NORMOCYTIC ANEMIAS WITH PREDOMINANT EXTRAVASCULAR HEMOLYSIS
A. Autosomal recessive mutation in β
chain of hemoglobin
1. Normal glutamic acid is replaced by lysine. 2. Less common than sickle cell disease
B. Presents with mild anemia due to extravascular hemolysis
C. Characteristic HbC crystals are seen in RBCs on blood smear (Fig. 5.10)
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)
NORMOCYTIC ANEMIAS WITH PREDOMINANT INTRAVASCULAR HEMOLYSIS
A. Acquired defect in myeloid stem cells resulting in absent
glycosylphosphatidylinositol (GPI); renders cells susceptible to destruction by complement
1. Blood cells coexist with complement.
2. Decay accelerating factor (DAF) on the surface of blood cells protects against
complement-mediated damage by inhibiting C3 convertase. 3. DAF is secured to the cell membrane by GPI (an anchoring glycolipid). 4. Absence of GPI leads to absence of DAF, rendering cells susceptible to
complement-mediated damage.
B. Intravascular hemolysis occurs episodically, often at night during sleep.
1. Mild respiratory acidosis develops with shallow breathing during sleep and
activates complement. 2. RBCs, WBCs, and platelets are lysed. 3. Intravascular hemolysis leads to hemoglobinemia and hemoglobinuria
(especially in the morning); hemosiderinuria is seen days after hemolysis.
PNH test
Sucrose test is used to screen for disease; confirmatory test is the acidified serum test
or flow cytometry to detect lack of CD55 (DAF) on blood cells.
PNH main cause of death
Main cause of death is thrombosis of the hepatic, portal, or cerebral veins.
1. Destroyed platelets release cytoplasmic contents into circulation, inducing
thrombosis.
PNH complications
Complications include iron deficiency anemia (due to chronic loss of hemoglobin in the urine) and acute myeloid leukemia (AML), which develops in 10% of patients.
GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY
NORMOCYTIC ANEMIAS WITH PREDOMINANT INTRAVASCULAR HEMOLYSIS
A. X-linked recessive disorder resulting in reduced half-life of G6PD; renders cells
susceptible to oxidative stress
1. RBCs are normally exposed to oxidative stress, in particular H2O2•
2. Glutathione (an antioxidant) neutralizes H2O2, but becomes oxidized in the
process.
3. NADPH, a by-product of G6PD, is needed to regenerate reduced glutathione.
4. ↓G6PD ↓→ NADPH ↓→ r educed glutathione → oxidative injury by H2O2
→ intravascular hemolysis
2 variants of G6PD
B. G6PD deficiency has two major variants.
1. African variant - mildly reduced half-life of G6PD leading to mild
intravascular hemolysis with oxidative stress
2. Mediterranean variant - markedly reduced half-life of G6PD leading to marked intravascular hemolysis with oxidative stress
3. High carrier frequency in both populations is likely due to protective role against falciparum malaria
Heinz bodies
Occurs in G6PD
C. Oxidative stress precipitates Hb as Heinz bodies.
1. Causes of oxidative stress include infections, drugs (e.g., primaquine, sulfa drugs,
and dapsone), and fava beans.
2. Heinz bodies are removed from RBCs by splenic macrophages, resulting in bite
cells (Fig. 5.11).
3. Leads to predominantly intravascular hemolysis
G6PD presentation
Presents with hemoglobinuria and back pain hours after exposure to oxidative stress
screen for G6PD
Heinz preparation is used to screen for disease (precipitated hemoglobin can only
be seen with a special Heinz stain, Fig. 5.12); enzyme studies confirm deficiency
(performed weeks after hemolytic episode resolves).
IMMUNE HEMOLYTIC ANEMIA (IHA)
NORMOCYTIC ANEMIAS WITH PREDOMINANT INTRAVASCULAR HEMOLYSIS
A. Antibody-mediated (IgG or IgM) destruction of RBCs
AIHA IgG mediated pathology
B. IgG-mediated disease usually involves extravascular hemolysis.
1. IgG binds RBCs in the relatively warm temperature o f the central body (warm
agglutinin); membrane o f antibody-coated RBC is consumed by splenic
macrophages, resulting in spherocytes. 2. Associated with SLE (most common cause), CLL, and certain drugs (classically,
penicillin and cephalosporins)
i. Drug may attach to RBC membrane (e.g., penicillin) with subsequent binding
of antibody to drug-membrane complex ii. Drug may induce production of autoantibodies (e.g., α-methyldopa) that bind
self antigens on RBCs
3. Treatment involves cessation of the offending drug, steroids, IVIG, and, i f
necessary, splenectomy.
AIHA IgM mediated pathology
C. IgM-mediated disease can lead to intravascular hemolysis.
1. IgM binds RBCs and fixes complement in the relatively cold temperature of the
extremities (cold agglutinin). 2. RBCs inactivate complement, but residual C3b serves as an opsonin for splenic
macrophages resulting in spherocytes; extreme activation o f complement can lead
to intravascular hemolysis. 3. Associated with Mycoplasma pneumoniae and infectious mononucleosis.
Test for AIHA
Coombs test is used to diagnose IHA; testing can be direct or indirect.
1. Direct Coombs test confirms the presence of antibody- or complement-coated
RBCs. When anti-IgG/complement is added to patient RBCs, agglutination occurs i f RBCs are already coated with IgG or complement. This is the most important test for IHA.
2. Indirect Coombs test confirms the presence o f antibodies in patient serum. Anti-
IgG and test RBCs are mixed with the patient serum; agglutination occurs i f serum antibodies are present
MICROANGIOPATHIC HEMOLYTIC ANEMIA
A. Intravascular hemolysis that results from vascular pathology; RBCs are destroyed as
they pass through the circulation.
1. Iron deficiency anemia occurs with chronic hemolysis.
B. Occurs with microthrombi (TTP-HUS, DIC, HELLP), prosthetic heart valves, and
aortic stenosis; when present, microthrombi produce schistocytes on blood smear
(Fig. 5.13).
MALARIA
A. Infection of RBCs and liver with Plas modium (Fig. 5.14); transmitted by the female
Anophel es mosquito B. RBCs rupture as a part of the Plasmodium life cycle, resulting in intravascular
hemolysis and cyclical fever.
1. P falciparum - daily fever 2. P vivax and P ovale - fever every other day
C. Spleen also consumes some infected RBCs; results in mild extravascular hemolysis
with splenomegaly
Basic Principles of Anemia Due to underproduction
A. Decreased production of RB Cs by bone marrow; characterized by low corrected
reticulocyte count B. Etiologies include
1. Causes of microcytic and macrocytic anemia 2. Renal failure - decreased production of EPO by peritubular interstitial cells 3. Damage to bone marrow precursor cells (may result in anemia or pancytopenia)
parvovirus B19
underproduction
A. Infects progenitor red cells and temporarily halts erythropoiesis; leads to significant
anemia in the setting of preexisting marrow stress (e.g., sickle cell anemia).
B. Treatment is supportive (infection is self-limited).
Aplastic Anemia
Underproduction
A. Damage to hematopoietic stem cells, resulting in pancytopenia (anemia,
thrombocytopenia, and leukopenia) with low reticulocyte count
B. Etiologies include drugs or chemicals, viral infections, and autoimmune damage.
C. Biopsy reveals an empty, fatty marrow (Fig. 5.15).
D. Treatment includes cessation of any causative drugs and supportive care with
transfusions and marrow-stimulating factors (e.g., erythropoietin, GM-CSF,
and G-CSF).
1. Immunosuppression may be helpful as some idiopathic cases are due to
abnormal T-cell activation with release of cytokines. 2. May require bone marrow transplantation as a last resor
MYELOPHTHISIC PROCESS
underproduction
Pathologic process (e.g., metastatic cancer) that replaces bone marrow;
hematopoiesis is impaired, resulting in pancytopenia.
