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D&T - E1 > Pathoma - Red Blood Cell Disorders > Flashcards

Pathoma - Red Blood Cell Disorders Flashcards

1
Q

Anemia - Basic principles

A
  • Reduction in circulating RBC mass
  • Hemoglobin (Hb), hematocrit (Hct), and RBC count are used as surrogates for RBC mass, which are difficult to measure
  • Anemia is defined as 100 um^3)
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2
Q

Anemia - Signs and Symptoms

A

Anemia presents with signs and symptoms of hypoxia:

  • Weakness, fatigue, and dyspnea
  • Pale conjunctiva and skin
  • Headache and lightheadedness
  • Angina, especially with preexisting coronary artery disease
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3
Q

Microcytic Anemia - Basic Principles

A
  • Anemia with MCV
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4
Q

Microcytic Anemia - Subtypes

A
  • Iron deficiency anemia
  • Anemia of chronic disease
  • Sideroblastic anemia
  • Thalassemia
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5
Q

Iron Deficiency Anemia

A
  • Due to decreased levels of iron
  • ↓ iron → ↓ heme → ↓ hemoglobin → microcytic anemia
  • MOST COMMON TYPE OF ANEMIA → lack of iron is the most common nutritional deficiency in the world, affecting roughly 1/3 of the world’s population
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6
Q

Iron Deficiency Anemia - Iron absorption

A

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 transporters (DMT1); the heme form is more readily absorbed
  2. Enterocytes transport irons across the cell membrane into blood via ferroportin
  3. Transferrin transports iron in the blood and delivers it to the liver and bone marrow macrophages for storage
  4. Stored intracellular iron is bound to ferritin, which prevents iron from forming free radicals via the Fenton reaction
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7
Q

Iron Deficiency Anemia - Laboratory measurements of iron status

A
  • SERUM IRON: measure of iron in the blood
  • TOTAL IRON BINDING CAPACITY (TIBC): measure of transferrin molecules in the blood
  • % SATURATION - percentage of transferrin molecules that are bound by iron (normal is 33%)
  • SERUM FERRITIN - reflects iron stores in macrophages and the liver
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8
Q

Iron Deficiency Anemia - Causes

A

Iron deficiency is usually caused by dietary lack or blood loss:

  • 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 in iron absorption by maintaining the Fe2+ state, which is more readily absorbed than Fe3+)
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9
Q

Iron Deficiency Anemia - Stages of Iron Deficiency

A
  • STORAGE OF 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
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10
Q

Iron Deficiency Anemia - Clinical features

A
  • Anemia
  • Koilonychia
  • Pica
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11
Q

Iron Deficiency Anemia - Laboratory findings

A
  • Microcytic, hypochromic RBCs with ↑ red cell distribution width (RDW)
  • ↓ ferritin, ↑ TIBC, ↓ serum iron, ↓ % saturation
  • ↑ free erythrocyte protoporphyrin (FEP)
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12
Q

Iron Deficiency Anemia - Treatment

A

Involves supplemental iron (ferrous sulfate)

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13
Q

Iron Deficiency Anemia - Plummer-Vinson Syndrome

A
  • Iron deficiency anemia with esophageal web and atrophic glossitis
  • Presents as anemia, dysphagia, and beefy red tongue
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14
Q

Anemia of Chronic Disease

A
  • Anemia associated with chronic inflammation (eg endocarditis or autoimmune conditions) or cancer
  • Most common type of anemia in hospitalized patients
  • Chronic disease results in production of acute phase reactants from the liver, including HEPCIDIN
  • 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
  • ↓ available iron → ↓ heme → ↓ hemoglobin → microcytic anemia
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15
Q

Anemia of Chronic Disease - Laboratory finidngs

A
  • ↑ ferritin, ↓ TIBC, ↓ serum iron, and ↓ % saturation

- ↑ free erythrocyte protoporphyrin (FEP)

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16
Q

Anemia of Chronic Disease - Treatment

A

Involves addressing the underlying cause

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17
Q

Sideroblastic Anemia

A
  • Anemia due to defective protoporphyrin synthesis

- ↓ protoporphyrin → ↓ heme → ↓ hemoglobin → microcytic anemia

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18
Q

Sideroblastic Anemia - Protoporphyrin synthesis

A
  1. Aminolevulinic acid synthetase (ALAS) converts succinyl CoA to aminolevulinic acid (ALA) using vitamin B6 as a cofactor (RATE LIMITING STEP)
  2. Aminolevulinic acid dehydratase (ALAD) converts ALA to porphobilinogen
  3. Additional reactions convert porphobilinogen to protoporphyrin
  4. Ferrochelatase attaches protoporphyrin to iron to make heme (FINAL REACTION; OCCURS IN MITOCHONDRIA)

Iron is transferred to erythroid precursors and enters the mitochondria to form heme. If protoporphyrin is deficient, iron remains trapped in mitochondria

  • Iron laden mitochondria form a ring around the nucleus of erythroid precursors
  • These cells are called RINGED SIDEROBLASTS
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19
Q

Sideroblastic Anemia - Causes

A

Sideroblastic anemia can be congenital or acquired

  • Congenital defect most commonly involves ALAS (rate limiting enzyme)
  • Acquired causes include: alcoholism (mitochondrial poison), lead poisoning (inhibits ALAD and ferrochelatase), vitamin B6 deficiency (required cofactor for ALAS; most commonly seen as a side effect of isoniazid treatment for tuberculosis)
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20
Q

Sideroblastic Anemia - Laboratory findings

A

↑ ferritin, ↓ TIBC, ↑ serum iron, ↑ % saturation

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21
Q

Thalassemia

A
  • Anemia due to decreased synthesis of the globin chains of hemoglobin
  • ↓ globin → ↓ hemoglobin → microcytic anemia
  • Inherited mutation
  • Carrers are protected against Plasmodium falciparum malaria
  • Divided into α and β thalassemia based on decreased production of alpha or beta globin chains
  • Normal types of hemoglobin are HbF (α2γ2), HbA (α2β2), HbA2 (α2δ2)
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22
Q

α Thalassemia

A
  • Usually due to gene deletion, 4 alpha genes are present on chromosome 16
  • 1 gene deleted: asymptomatic
  • 2 genes deleted: milk anemia with ↑ RBC count; cis deletion is associated with an increased risk of severe thalassemia in offspring
  • Cis deletion is when both deletions occur on the same chromosome; SEEN IN ASIANS
  • Trans deletion is when one deletion occurs on each chromosome; SEEN IN AFRICANS, INCLUDING AFRICAN AMERICANS
  • 3 genes deleted: severe anemia; β chains form tetramers (HbH) that damage RBCs; HbH is seen on electrophoresis
  • 4 genes deleted: lethal in utero (hydrops fetalis); γ chains form tetramers (Hb Barts) that damage RBCs; Hb Barts is seen on electrophoresis
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23
Q

β Thalassemia

A
  • Usually due to gene mutations (point mutation in promoter or splicing sites); seen in individuals of African and Mediterranean descent
  • 2 β genes are present on chromosome 11
  • Mutations result in absent βo or diminished β+ production of the β globin chain
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24
Q

β Thalassemia Minor

A

Minor β/β+ is the mildest for of disease and is usually asymptomatic with an increased RBC count

  • Microcytic, hypochromic RBCs and target cells are seen on blood smear
  • Hemoglobin electrophoresis shows slightly decreased HbA with increased HbA2 (5%, normal 2.5%) and HbF (2%, normal 1%)
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25
Q

β Thalassemia Major

A

Major (βo/βo) is the most severe form of disease and presents with severe anemia a few moths after birth; high HbF (α2γ2) at birth is temporarily protective

  • Unpaired α chains precipitate and damage RBC membrane, resulting in ineffective erythropoiesis and extravascular hemolysis (removal of circulating RBCs by the spleen)
  • Massive erythroid hyperplasia ensues resulting in (1) expansion of hematopoiesis into the skull (reactive bone formation leads to ‘CREWCUT’ appearance on x-ray) and facial bones (‘chipmunch facies’), (2) extramedullay hematopoiesis with hepatosplenomegaly and (3) risk of aplastic crisis with parvovirus B19 infection of erythroid precursors
  • Chronic transfusions are often necessary; leads to risk for secondary hemochromatosis
  • Smear shows microcytic, hypochromic RBCs with target cells and nucleated RBCs
  • Electrophoresis shows HbA2 and HbF with little or no HbA
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26
Q

Macrocytic Anemia - Basic Principles

A
  • Anemia with MCV > um^3
  • Most commonly due to folate or vitamin B12 deficiency (megaloblastic anemia)
  • Other causes of macrocytic anemia (without megaloblastic change) include alcoholism, liver disease, and drugs
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27
Q

Macrocytic Anemia - Basic Principles - Importance of folate and B12

A

Folate and vitamin B12 are necessary for synthesis of DNA precursors

  • Folate circulates in the serum as methyltetrahydrofolate (methyl THF)
  • Removal of the methyl group allows for participation in the synthesis of DNA precursors
  • Methyl group is transferred to vitamin B12 (cobalamin)
  • Vitamin B12 then transfers it to homocytstein, producing methionine

Lack of folate or vitamin B12 impairs synthesis of DNA precursors

  • Impaired division and enlargement of RBC precursors leads to megaloblastic anemia
  • Impaired division of granulocytic precursors leads to hypersegmented neutrophils
  • Megaloblastic change is also seen in rapidly-dividing (eg intestinal) epithelial cells
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28
Q

Macrocytic Anemia - Folate Deficiency

A
  • Dietary folate is obtained from green vegetables and some fruits (absorbed in jejunum)
  • Folate deficiency develops within months, as body stores are minimal
  • Causes include poor diet (eg alcoholics and elderly), increased demand (eg pregnancy, cancer and hemolytic anemia) and folate antagonists (eg methotrexate, which inhibits dihydrofolate reductase)
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29
Q

Macrocytic Anemia - Folate Deficiency - Clinical and Laboratory Findings

A
  • Macrocytic RBCs and hypersegmented neutrophils (>5 lobes)
  • Glossitis
  • ↓ serum folate
  • ↑ serum homocysteine (increase risk for thrombosis)
  • Normal methylmalonic acid
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30
Q

Macrocytic Anemia - Vitamin B12 Deficiency

A

Dietary B12 is complexed to animal-derived proteins

  • Salivary gland enzymes (eg amylase) liberate B12, which is then bound by R-binder (also from the salivary gland) and carried through the stomach
  • Pancreatic proteases in the duodenum detach B12 from R-binder
  • B12 binds intrinsic factor (made by gastric parietal cells) in the small bowel; intrinsic factor-B12 complex is absorbed in the ileum

B12 deficiency is less common than folate deficiency and takes years to develop due to large hepatic stores of B12

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31
Q

Macrocytic Anemia - Vitamin B12 Deficiency - Causes

A

Pernicious anemia is the most common cause of B12 deficiency
- Autoimmune destruction of parietal cells (body of stomach) leads to intrinsic factor deficiency

Other causes of B12 deficiency include pancreatic insufficiency and damage to the terminal ileum (eg Crohn’s disease or Diphyllobothrium latum (fish tapeworm))

Dietary deficiency is rare, except in vegans

32
Q

Macrocytic Anemia - Vitamin B12 Deficiency - Laboratory and Clinical Findings

A
  • Macrocytic RBCs with hypersegmented neutrophils
  • Glossitis
  • Subacute degeneration of the spinal cord
  • ↓ serum vitamin B12
  • ↑serum homocysteine (similar to folate deficiency), which increases the risk of thrombosis
  • ↑ methylmalonic acid (unlike folate deficiency)
33
Q

Macrocytic Anemia - Vitamin B12 Deficiency - Subacute degeneration of the spinal cord

A
  • Vitamin B12 is a cofactor for the conversion of methylmalonic acid to succinyl CoA (important in fatty acid metabolism)
  • B12 deficiency results in increased levels of methylmalonic acid, which impairs spinal cord myelinization
  • Damage results in poor propioception and vibratory sensation (posterior column) and spastic pareisis (lateral corticospinal tract)
34
Q

Normocytic Anemia

A
  • Anemia with normal sized RBCs (MCV = 80-100 um^3)
  • Due to increased peripheral destruction or underproduction
  • Reticulocyte count helps to distinguish between these 2 etiologies
35
Q

Normocytic Anemia - Reticulocytes

A

Young RBCs released from the bone marrow
- Identified on blood smear as larger cells with bluish cytoplasm (due to residual RNA)

Normal reticulocyte count

  • RBC lifespan is 120 days
  • Each day 1-2% of RBCs are removed from circulation and replaced by reticulocytes

A properly functioning marrow responds to anemia by increasing the RC to > 3%

RC, however, is falsely elevated in anemia

  • RC is measured as percentage of total RBCs
  • Decrease in total RBCs falsely elevates percentage of reticulocytes

RC is corrected by multiplying count by Hct/45

  • Corrected count > 3% indicates good marrow response and suggests peripheral destruction
  • Corrected count
36
Q

Normocytic Anemia - Peripheral RBC Destruction (Hemolysis)

A
  • Divided into extravascular and intravascular hemolysis

- Both result in anemia with a good marrow response

37
Q

Normocytic Anemia - Peripheral RBC Destruction (Hemolysis) - Extravascular Hemolysis

A

Extravascular hemolysis involves RBC destruction by the reticuloendothelial system (macrophages of the spleen, liver, and lymph nodes)

Macrophages consume RBCs and bread down hemoglobin

  • Globin is broken down into amino acids
  • Heme is broken down into iron and protopophyrin; iron is recycled
  • Protoporphyrin is broken down into unconjugated bilirubin, which is bound to serum albumin and delivered to the liver for conjugation and excretion into bile
38
Q

Normocytic Anemia - Peripheral RBC Destruction (Hemolysis) - Extravascular Hemolysis - Clinical and Laboratory Findings

A
  • Anemia with splenomegaly, jaundice due to unconjugated bilirubin, and increased risk for bilirubin gallstones
  • Marrow hyperplasia with corrected reticulocyte count > 3%
39
Q

Normocytic Anemia - Peripheral RBC Destruction (Hemolysis) - Intravascular Hemolysis

A

Involves destruction of RBCs within vessels

40
Q

Normocytic Anemia - Peripheral RBC Destruction (Hemolysis) - Intravascular Hemolysis - Clinical and Laboratory Findings

A
  • Hemoglobinemia
  • Hemoglobinuria
  • Hemosiderinuria (renal tubular cells pick up some of the hemoglobin that is filtered into the urin and break it down into iron, which accumulates as hemosiderin; tubular cells are eventually shed resulting in hemosiderinuria)
  • Decreased serum haptoglobin
41
Q

Normocytic Anemias with Predominant Extravascular Hemolysis

A
  • Hereditary Spherocytosis
  • Sickle Cell Anemia
  • Hemoglobin C
42
Q

Hereditary Spherocytosis

A

Inherited defect of RBC cytoskeleton membrane tethering proteins
- Most commonly involves ankyin, spectrin, or band 3

Membrane blebs are formed and lost over time

  • Loss of membrane renders cells round (spherocytes) instead of disc shaped
  • Spherocytes are less able to maneuver through splenic sinusoids and are consumed by splenic macrophages, resulting in anemia
43
Q

Hereditary Spherocytosis - Clinical and Laboratory Findings

A
  • Spherocytes with loss of central pallor
  • ↑ RDW and ↑ mean corpuscular hemoglobin concentration (MCHC)
  • Splenomegaly, jaundice with unconjugated bilirubin, and increased risk for bilirubin gallstones (extravascular hemolysis)
  • Increased risk for aplastic crisis with parvovirus B19 infection of erythroid precursors
44
Q

Hereditary Spherocytosis - Diagnosis

A

Diagnosed by osmotic fragility test, which reveals increased spherocyte fragility in hypotonic solution

45
Q

Hereditary Spherocytosis - Treatment

A
  • Splenectomy
  • Anemia resolves, but spherocytes persis and Howell-Jolly bodies (fragments of nuclear material in RBCs) emerge on blood smear
46
Q

Sickle Cell Anemia

A
  • Autosomal recessive mutation in β chain of hemoglobin
  • A single AA change replaces normal glutamate (hydrophilic) with valine (hydrophobic)
  • Gene is carried in 10% of individuals of African descent, likely due to protective role against falciparum malaria
  • Sickle cell disease arises when 2 abnormal β genes are present
  • Results in > 90% HbS in RBCs
47
Q

Sickle Cell Anemia - Sickle cell formation

A

HbS polymerizes when deoxygenated; polymers aggregate into needle-like stuctures, resulting in sickle cells

  • Increased risk of sickling occurs with hypoxemia, dehydration and acidosis
  • HbF protects against sickling
  • High HbF at birth is protective for the first few months of life
  • Treatment with hydroxyurea increases levels of HbF``
48
Q

Sickle Cell Anemia - Complications related to RBC membrane damage

A
  • EXTRAVASCULAR HEMOLYSIS: reticuloendothelial system removes RBCs with damaged membranes, leading to anemia, jaundice with unconjugated hyperbilirubinemia, and increased risk for bilirubin gallstones
  • INTRAVASCULAR HEMOLYSIS: RBCs with damaged membranes dehydrate, leading to hemolysis with decreased haptoglobin and target cells on blood smear
  • MASSIVE ERTHYROID HYPERPLASIA ENSUES RESULTING IN: expansion of hematopoiesis into the skull (‘crewcut’ appearance on x-ray) and facial bones (‘chipmunk facies’), extramedullary hematopoiesis with hepatomegaly, risk of aplastic crisis with parvovirus B19 infection of erythroid precursors
49
Q

Sickle Cell Anemia - Vaso-occlusion

A
  • DACTYLITIS: swollen hands and feed due to vaso-occlusive infarcts in bones; common presenting sign in infacts
  • AUTOSPLENECTOMY: shrunken, fibrotic spleen; consequences include: increased risk of infection with encapsulated organisms such as Streptococcus pneumonia and Haemophilius influenza (most common cause of death in children); affected children should be vaccinated by 5 years; increased risk of Salmonella paratyphi osteomyelitis; Howell-Jolly bodies on blood smear
  • ACUTE CHEST SYNDROME: vaso-occlusion in pulmonary microcirculation: presents with chest pain, dyspnea, and lung infiltrates; often precipitated by pneumonia; most common cause of death in adult patients
  • PAIN CRISIS
  • RENAL PAPILLARY NECROSIS: results in gross hematuria and proteinuria
50
Q

Sickle Cell Anemia - Trait

A

Sickle cell trait is the presence of 1 mutated and 1 normal β chain; results in

51
Q

Sickle Cell Anemia - Laboratory Findings

A
  • Sickle cells and target cells are seen on blood smear in sickle cell disease, but not in sickle cell trait
  • Metabisulfite screen causes cells with any amount of HbS to sickle; positive in both disease and trait
  • Hb electrophoresis confirms the presence and amount of HbS
  • DISEASE: 90% HbS, 8% HbF, 2%HbA2, NO HbA
  • TRAIT: 55% HbA, 43% HbS, 2% HbA2
52
Q

Hemoglobin C

A

Autosomal recessive mutation in β chain of hemoglobin

  • Normal glutamate replaced by lysine
  • Less common than sickle cell disease

Presents with mild anemia due to extravascular hemolysis

Characteristic HbC crystals are seen in RBCs on blood smear

53
Q

Normocytic Anemia with Predominant Intravascular Hemolysis

A
  • Paroxysmal Nocturnal Hemoglobinuria (PNH)
  • Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
  • Immune Hemolytic Anemia (IHA)
  • Microangiopathic Hemolytic Anemia
  • Malaria
54
Q

Paroxysmal Nocturnal Hemoglobinuria (PNH)

A

Acquired defect in myeloid stem cells resulting in absent glycosylphosphatidylinositol (GPI); renders cells susceptible to destruction by complement

  • Blood cells coexist with complement
  • Decay accelerating factor (DAF) on the surface of RBCs protects against complement mediated damage by inhibiting C3 convertase
  • DAF is secured to the membrane by GPI (an anchoring glycolipid)
  • Absence of GPI leads to absence of DAF, rendering cells susceptible to complement mediated damage
55
Q

Paroxysmal Nocturnal Hemoglobinuria (PNH) - Intravascular hemolysis

A

Intravascular hemolysis occurs episodically, often at night during sleep

  • Mild respiratory acidosis develops with shallow breathing during sleep and activates complement
  • RBCs, WBCs and platelets are lysed
  • Intravascular hemolysis leads to hemoglobinemia and hemoglobinuria (especially in the morning)
  • Hemosiderinuria is seen days after hemolysis
56
Q

Paroxysmal Nocturnal Hemoglobinuria (PNH) - Diagnosis

A
  • 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

57
Q

Paroxysmal Nocturnal Hemoglobinuria (PNH) - Cause of death

A

Main cause of death is thrombosis of the hepatic, portal or cerebral veins
- Destroyed platelets release cytoplasmic contents into circulation, inducing thrombosis

58
Q

Paroxysmal Nocturnal Hemoglobinuria (PNH) - Complications

A
  • Iron deficiency anemia (due to chronic loss of hemoglobin in the urine)
  • Acute myeloid leukemia (AML), which develops in 10% of patients
59
Q

G6PD Deficiency

A

X linked recessive disorder resulting in reduced half-life of G6PD; renders cells susceptible to oxidative stress

  • RBCs are normally exposed to oxidative stress, particularly H2O2
  • Glutathione (an antioxidant) neutralizes H2O2 but becomes oxidized in the process
  • NADPH, a by product of G6PD, is needed to regenerate glutathione
  • ↓ G6PD → ↓ NADPH → ↓ reduced glutathione → oxidative injury by H2O2 → intravascular hemolysis
60
Q

G6PD Deficiency - Variants

A

African variant:
- Mildly reduced half-life of G6PD leading to mild-intravascular hemolysis with oxidative stress

Mediterranean variant:
- Markedly reduced half-life of G6PD leading to marked intravascular hemolysis with oxidative stress

High carrier frequency in both populations is likely due to protective role against falciparum malaria

61
Q

G6PD Deficiency - Heniz Bodies

A

Oxidative stress precipitates Hb as Heinz bodies

  • Causes of oxidative stress include infections, drugs (eg primaquine, sulfa drugs and dapsone) and fava beans
  • Heinz bodies are removed from RBCs by splenic macrophages, resulting in bite cells
  • Leads to predominantly intravascular hemolysis
62
Q

G6PD Deficiency - Presentation

A
  • Hemoglobinuria

- Back pain hours after exposure to oxidative stress

63
Q

G6PD Deficiency - Diagnosis

A
  • Heinz preparation is used to screen for disease (precipitated (hemoglobin can only be seen with a special Heinz stain)
  • Enzyme studies confirm deficiency (performed weeks after hemolytic episode resolves)
64
Q

Immune Hemolytic Anemia (IHA)

A

Antibody mediated (IgG or IgM) destruction of RBCs

65
Q

Immune Hemolytic Anemia (IHA) - IgG mediated

A

IgG mediated disease usually involves extravascular hemolysis

  • IgG binds RBCs in the relatively warm temperature of the central body (warm agglutinin); membrane of antibody coated RBC is consumed by splenic macrophages, resulting in spherocytes
  • Associated with SLE (most common cause), CLL, and certain drugs (classically, penicillin and cephalosporins)
  • Drugs may attach to RBC membrane with subsequent binding of antibody to drug-membrane complex
  • Drug may induce production of autoantibodies (eg α-methyldopa) that bind self antigens on RBCs
  • Treatment involves cessation of the offending drug, steroids, IVIG and if necessary, splenectomy
66
Q

Immune Hemolytic Anemia (IHA) - IgM mediated

A

IgM mediated disease also usually involves extravascular hemolysis

  • IgM binds RBCs and fixes complement in the relatively cold temperatures of the extremities (cold agglutinin)
  • RBCs inactivate complement, but residual C3b serves as an opsonin for splenic macrophages resulting in spherocytes; extreme activation of complement can lead to intravascular hemolysis
  • Associated with Mycoplasma pneumonia and infectious mononucleosis
67
Q

Immune Hemolytic Anemia (IHA) - Diagnosis

A

Coombs test is used to diagnose IHA; testing can be direct or indirect

68
Q

Immune Hemolytic Anemia (IHA) - Diagnosis - Direct Coombs Test

A

Direct Coombs Test

  • Confirms the presence of antibody or complement coated RBCs
  • When anti-IgG/complement is added to patients RBCs, agglutination occurs if RBCs are already coated with IgG or complement
  • This is the most important test for IHA
69
Q

Immune Hemolytic Anemia (IHA) - Diagnosis - Indirect Coombs Test

A

Indirect Coombs Test

  • Confirms the presence of antibodies in patient serum
  • Anti-IgG and test RBCs are mized with the patient serum
  • Agglutination occurs if serum antibodies are present
70
Q

Microangiopathic Hemolytic Anemia

A

Intravascular hemolysis that results from vascular pathology

  • RBCs are destroyed as they pass through circulation
  • Iron deficiency anemia occurs with chronic hemolysis

Occurs with microthrombi (TTP-HUS, DIC, HELLP), prosthetic heart valves, and aortic stenosis
- When present, microthrombi produce schistocytes on blood smear

71
Q

Malaria

A

Infection of RBCs and liver with Plasmodium, transmitted by the female Anopheles mosquito

RBCs rupture as a part of the Plasmodium life cycle, resulting in intravascular hemolysis and cyclical fever

  • P falciparum - daily fever
  • P vivax and P ovale - fever every other day

Spleen also consumes some infected RBCs; resulting in mild extravascular hemolysis with splenomegaly

72
Q

Anemias due to underproduction

A

Decreased production of RBCs by bone marrow; characterized by low corrected reticulocyte count

Etiologies include:

  • Causes of microcytic and macrocytic anemia
  • Renal failure: decreased production of EPO by peritubular interstitial cells
  • Damage to bone marrow precursor cells (may result in anemia or pancytopenia)

Includes:

  • Parvovirus B19
  • Aplastic anemia
  • Myelophthisic process
73
Q

Parvovirus B19

A
  • Infects progenitor red cells and temporarily halts erythropoiesis; leads to significant anemia in the setting of preexisting marrow stress (eg sickle cell anemia)
  • Treatment is supportive (infection is self-limited)
74
Q

Aplastic anemia

A
  • Damage to hematopoietic stem cells, resulting in pancytopenia (anemia, thrombocytopenia, and leukopenia) with low reticulocyte count
  • Etiologies include drugs or chemicals, viral infections, and autoimmune damage
  • Biopsy reveals an empty, fatty marrow
75
Q

Aplastic anemia - Treatment

A

Treatment includes cessation of any causative drugs and supportive care with transfusions and marrow stimulating factors (eg erythropoietin, GM-CSF, and G-CSF)

  • Immunosuppression may be helpful as some idiopathic cases are due to abnormal T cell activation with release of cytokines
  • May require bone marrow transplantation as a last resort
76
Q

Myelophthisic Process

A

Pathologic process (eg metastatic cancer) that replaces bone marrow; hematopoiesis is impaired, resulting in pancytopenia

D&T - E1 (11 decks)

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