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Heme/Onc Pathoma > Chapter 5: Anemia COPY COPY > Flashcards

Chapter 5: Anemia COPY COPY Flashcards

1
Q

How does iron transport work in the body?

A
  1. Enterocyte takes up iron from the gut
  2. Enterocyte decides whether to the send iron into the blood or not
    • The body has the ability to take up iron but does nto have the ability to get rid of iron so only want to bring in iron to the body when it is needed
    • Ferroportin is the transporter used to move iron from the enterocyte into the body
  3. Once iron gets into the blood, iron binds to Transferrin
    • ​​Unbound iron can generate free radicals so it is always bound
  4. Transferrin trasnports iron and delivers it to the liver and bone marrow macrophages for storage
    • In the macrophages, iron is bound to ferritin to prevent iron from generating free radicles
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2
Q

What is ferritin needed for?

A

Iron storage in macrophages

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3
Q

What are target cells?

A
  • membrane gets damaged so cell loses fluid and shirnks
  • as a result, a bleb of hemoglobin can form in the middle of the cell
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4
Q

What is the cause of microcytic anemias?

A
  • Decreased production of hemoglobin
  • Microcytosis is due to an extra division which occurs to maintain hemoglobin concentration
    • Erythroblast divides many times to make RBC but can get microcytic anemia if it divides too many times
    • If there is not enough hemoglobin, RBCs can try to maintain hemoglobin concentration by dividing an extra time
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5
Q

What is hemoglobin composed of?

A
  1. Heme
    • Iron
    • Protoporphyrin
  2. Globin
  • Decrease in any of these components can lead to microlytic anemia
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6
Q

What are the five major microcytic anemias?

A

T: Thalassemia

A: Anemia of Chronic Disease

I: Iron Deficiency

L: Lead Poisoning

S: Sideroblastic Anemia

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7
Q

What are the most common causes of iron deficiency?

A

Infants: Breast feeding (Little iron in breast milk)

Children: poor diet

Adults (20-50 yrs): peptic ulcer disease in males and menorrhagia or pregancy in females

Elderly: colon polyps/carincoma in the western world

  • hookworm (Ancylostoma duodenale and Necator americanus) in the developing work

Other causes: malnutrition, malabsorbtion, gastrectomy

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8
Q

Why can a gastrectomy cause iron deficiency?

A

FE2+ goes in 2 the body

  • Fe2+ is more easily absorbed than Fe3+
  • acid maintains Fe2+ state
  • gastrectomy, where a patient loses part of the stomach can result in decreased acid resulting in decreased bioavailability since iron is stuck in Fe3+ state
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9
Q

What are the stages of iron deficiency?

A
  1. Use up all stored iron
    • measure of storage iron is ferritin
    • when storage iron is depleted, ferritin goes down
    • since ferritin goes down, TBC (total binding capacity) goes up
      • TBC measures transferrin
    • whenever ferritin is low, the liver will pump out more transferrin to go find iron
  2. Serum iron is used up
    • serum iron decreases
    • % saturation decreases
      • if serum iron is being consumed, less transferrin molecules in the serum will have iron bound to it
      • normal saturation is 33% (1 of 3 transferrin have iron bound to it)
  3. Normalcytic anemia
    • as the bone marrow begins to recognize that iron isn’t available to make heme, it will make a sacrafice
    • prefers making quality RBCs even if there are less
  4. Microcytic hypochromic anemia
    • severe anemia
    • patient develops inability to make normal RBCs
    • bone marrow is making smaller cells with less hemoglobin
    • hypochromic: less color b/c less hemoglobin
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10
Q

What is RDW?

A
  • RDW measures spectrum of RBC size
  • if there is a wide spectrum in RBC size, the RDW would be high
  • there is nomral and small cells in iron deficiency so has high RDW
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11
Q

What are the lab findings for iron deficiency?

A
  • microcytic hypochromatic RBCS with increased RDW
  • Decrease ferritin, Increased TIBC, decrease serum iron, decrease % saturation
  • Increase in free erythrocyte protoporphyrin
    • Heme = iron + protoporphyrin
      • in iron deficiency, iron is down but there is no issue with protoporphyrin
      • some of the protoporphyrin won’t be bound to iron b/c there isn’t enough so some protoporphyrin will float in the serum freely
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12
Q

What is the treatment for iron deficiency?

A

Ferrour sulfate: iron supplementation and treat underlying cause

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13
Q

Plummer-Vinson Syndrome

A
  • iron deficiency anemia with esophageal web and atrophic glossitis
    • esophageal web: mucosal protrusions in the esophagus
    • blocks the esophagus so can choke on food
  • presents as anemia, dysphagia and beefy red tongue
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14
Q

What does hepcidin do?

A
  • Sequesters iron in storage sites so it can’t be used: prohibits iron from being used
  • purpose of hepcidin is to prevent bacteria from acessing iron b/c they use it for their survival
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15
Q

What is anemia of chronic disease?

A
  • anemia associated with chronic inflammation (ex. endocarditis or autoimmune) 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
      2. Suppressing erythropoietin production
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16
Q

What are the lab findings in anemia of chronic disease?

A
  • Ferratin levels are elevated
    • storage iron piles up so ferritin levels are high
  • Transferrin levels are decreased
    • anytime ferritin is high, TIBC will go down
    • bone marrow can’t use iron stored in macrophages so it will use the iron in the serum
  • Serum iron is decreased
  • % saturation is decreased
  • Increase in free erythrocyte protoporphyrin
    • Heme = Fe + protoporphyrin
      • have decreased iron but proto is fine so have proto free in plasma
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17
Q

What is the cause of sideroblastic anemia?

A
  • defective protoporphyrin synthesis
  • iron is transferred to erythroid precursors and enters the mitochondria to form heme
  • if protophorphyrin is deficient, iron remains trapped in the mitochondria
    • results in formation of ringed sideroblasts: iron accumulating in a circle around nucleus
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18
Q

Protoporphyrin Synthesis

A
  1. Aminolevulinic acid synthetase (ALAS) converts succinyl CoA to aminolevulinic avid (ALA)
    • rate limiting step
    • Vitamin B6 is a cofactor
  2. Aminolevulinic acid dehydratase (ALAD) converts ALA to porphobilinogen
  3. Additional reactions convert prophobilinogen to protoporphyrin
  4. Ferrochelastase attaches protophorpyrin to iron to make heme
    • this takes place in the mitochondria
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19
Q

What are the causes of sideroblastic anemia?

A
  • congential defect most commonly involves ALAS (rate limiting step)
  • Acquired causes include
    • Alcoholism: mitochondrial poison
    • Lead poisoning: inhibits ALAD (porphobilinogen formation) and ferrochelatase (attaches iron to heme)
    • Vitamin B6 deficiency: required cofactor for ALAS
      • most commonly seen as a side ffect of isoniazid treatment for TB
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20
Q

Lab Findings for Sideroblastic Anemia

A
  • Ferratin levels increased
    • iron is trapped in the mitochondria
  • TIBC levels decreased
  • Serum levels increased
    • tons of iron in the mitochondria leads to cells dying and iron leaking out into the serum
  • % saturation increased
  • Iron overloaded state
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21
Q

What causes a-Thalassemia and what are the different versions of it?

A
  • usually due to a gene deletion
  • 4 alpha genes are present on chromosome 16
  1. One gene deleted: asymptomatic
  2. Two genes deleted: mild anemia with increased RBC count
    • Cis deletion: deletion on same chromsome: seen in Asians: associated with increased risk of severe thalassemia in offspring
    • Trans deletion: deletion on each chromsome: seen in Africans
  3. Three genes deleted: severe anemia
    • Beta chains form tetramers that damage RBCs
    • HbH seen on electrophoresis
  4. Four genes deleted: lethal in utero (hydrops fetalis)
    • gamma chains form tetramers (Hb Barts) that damage RBC
    • Hb Barts seen on electrophoresis
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22
Q

What type of mutation is found in beta Thalassemia patients?

A
  • point mutations in promoter or splicing sites on chromosome 11
  • mutations result in absent (B0) or diminished (B+) production of the B globin chain
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23
Q

What are the findinigs associated with B-Thalassemia minor (B+/B+)?

A
  • mildest form of the disease and 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 an increase in HbA2 and HbF
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24
Q

What are the clinical findings in B-Thalassemia Major (B+/B+)?

A
  • Most severe form of the disease and presents with severe anemia a few months after birth
    • high HbF at birth is temporarily protective
  • Unpaired alpha chains precipitate and damage RBC membrane resulting in ineffective erythropoiesis and extravascular hemolysis
    • Damaged RBCs are destroyed by the spleen
  • Massive erythroid hyperplasia ensues causing:
    1. Expansion of hematopoiesis into the skull (reactive bone fomration leads to crewcut appearance on X-ray) and facial bones (chipmunk faces)
    2. Extramedullary hematopoiesis with hepatosplenomegaly
    3. Risk of aplastic crisis with parovirus B19 infection of erythroid precursors
      • have to shut down RBC production which is a problem for someone with very few RBCs to begin with
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25
Q

What are the lab findings in B-Thalassemia Major (B+/B+)?

A
  • Smear shows microlytic, hypochromic RBCs with target cells (cells that have a bleb of membrane in the middle of the RBC) and nucleated RBCs
    • If RBCs are made in an abnormal location, some nucleated RBCs can escape into the blood
  • Electrophoresis shows HbA2 and HbF2 with little or no HbA
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26
Q

How is Folate and Vitamin B12 involved with DNA precursor formation?

A
  1. THF is absorbed and quickly methylated in the body
    • Needs to lsoe methy group to form DNA precursors
  2. Vitamin B12 takes the methyl group
  3. Vitamin B12 gives the methyl group to homcysteine forming methionine
  • If there is a folate (THF) deficiency, no DNA precursors will be made
  • If there is no Vitamin B12, THF can’t pass the methyl group off and can’t participate in DNA precursor synthesis
27
Q

What effect does folate or Vitamin B12 deficiency have on RBCs? What other types of cells are affected?

A
  • Impaired division and enlargement of RBC precursors leads to megaloblastic anemia
    • one less division occurs b/c there isn’t enough DNA precursor available to continue dividing
  • Impaired division of granulocytic precursors leads to hypersegmented neutrophils
  • Megaloblastic change is also seen in rapidly-dividing epithelial cells
28
Q

What are the causes of macrocytic anemia?

A
  • Major cause is folate or B12 deficiency
  • Other causes of macrocytic anemia without megaloblastic change include alcoholism, liver disease and drugs
29
Q

What are the causes of folate deficiency and how long does it take to develop?

A
  • Foliate deficiency develops within months as body stores are minimal
  • Causes include poor diet, increased demand (pregnancy, cancer, and hemolytic anemia), and folate antagonists (methotrexate which inhibits dihydrofolate reductase)
30
Q

What are the clinical and laboratory findings associated with folate deficiency?

A
  • Macrocytic RBCs and hypersegmented neutrophils (more than 5 lobes)
  • Glossitis: inflammation of the tongue
  • Decrease in serum folate
  • Increase in serum homocysteine
    • if there is no folate, can’t pass methyl group to Vitamin B12
    • As a result, homocysteine can’t combine with a methyl group and will be stuck as homocysteine
  • Normal Methylmalonic Acid
    • Methylmalonic acid is converted to succinyl CoA by Vitamin B12
    • will be normal in these patients b/c B12 is normal
31
Q

How is Vitamin B12 absorbed and stored?

A
  • B12 gets cleaved from the animal protein and gets boudn to R-Binder
    • R-Binder is produced by the salivary glands
  • B12/R-Binder travel through the esophagus and stomach together to get to the small bowel
  • Pancreatic proteases in the duodenum cleave R-Binder from B12
  • B12 then binds to intrinsic factor
    • intrinsic factor is produced in the partietal cells in the body of the stomach
  • B12 and intrinsic factor are absorbed in the ileum
32
Q

How long does it take for Vitamin B12 deficiency to have an effect?

A
  • less common than folate deficiency
  • Takes years to develop bc of large hepatic stores of vitamin B12
33
Q

What are the causes of Vitamin B12 deficiency?

A
  • Pernicious anemia is the most common cause of vitamin B12 deficiency
    • autoimmune destruction of parietal cells (body of stomach) leads to intrinsic factor deficiency
    • need intrinsic factor to bind VB12 b/c the ileum recognizes the VB12 and IF complex: complex is what is absorbed
  • Pancreatic insufficiency
    • Need pancreatic proteases to cleave R-Binder from VB12 so it can bind to intrinsic factor
  • Damage to Terminal Ileum
    • Place where VB12 is stored
  • Dietary deficiency is rare except in vegans
34
Q

Parietal Cell Ps

A
  1. Have proton pumps (makes stomach acid)
  2. Pink
  3. Associated with Pernicious anemia
35
Q

Clinical and lab findings for Vitamin B12 deficiency

A
  • Macrocytic RBCs with hypersegmented neutrophils
  • Glossitis
  • Subacute combined degeration of the spinal cord
    • Vitamin B12 is a cofactor for the conversion of methylmalonic acid to succinyl CoA
    • Vitamin V12 deficiency results in increased levels of methylmalonic acid, which impairs spinal cord myelinization
    • damage results in poor proprioception and vibratory sensation and spastic paresis
  • Decreased serum B12
  • Increased serum homocysteine which increases risk for thrombosis
    • if VB12 is not present, can’t pass methyl group to homocysteine so will be stuck as homocysteine
  • Increase in Methylmalonic acid (unlike folate deficiency)
36
Q

What are the two causes of normocytic anemias and how can they be distinguished from each other?

A
  • Due to increased peripheral destruction of RBCs or underproduction of RBCs
  • Reticulocyte count can help distinguish
    • Reticulocytes are young RBCs released from the bone marrow
    • identified on blood smear as larger cell with bluish cytoplasm (due to resideual RNA)
    • Normal reticulocyte count is 1-2%
    • a proplry functioning marrow responds to anemia by increasing the reticulocyte count to >3%
    • If corrected count is greater than 3%, bone marrow is intact and cells are being destroyed
    • If corrected count is less than 3%, bone marrow is not working properly
37
Q

Reticulocyte Count Correction

A
  • RC is corrected by multiphlying reticulocyte count by Hematocrit/45
38
Q

What is the process of extravascular hemolysis?

A
  • Involves RBC destruction by the reticuloendothelial system
    • macrophages of the spleen, liver and lymph
  • Macrophages consume and break down hemoglobin
    • Globin is broken down into amino acids
    • Heme is broken down into iron and protoporphyrin
      • Iron is recycled
      • Protoporphyrin is broken down into unconjugated bilirubin which is bound to serum albumin and delivered to the liver for cojugation and excretion into bile
39
Q

What are the clinical and lab findings associated with extravascular hemolysis?

A
  • Anemia with splenomegaly since spleen is consuming the RBCs
  • Jaundice due to unconjugated bilirubin and increased risk for bilirubin gallstones
    • liver can only conjugate a certain amount of bilirubin at a time
    • liver can’t conjugate the excess bilirubin so its floats around in the blood (jaundice)
    • eventually, liver will conjugate bilirubin and throw it into bile so get super saturation of bilirubin in the bile
      • increases risk of gallstones
  • Marrow hyperplasia with corrected reticulocyte count >3%
    • bone marrow is healthy and increases production of cells
40
Q

What is intravascular hemolysis and what are the clinical/lab findings associated with it?

A
  • destruction of RBCS within vessels
  • Clinical/lab findings include:
    • hemoglobinemia: hemoglobin leaks into blood
    • hemoglobinuria: hemoglobin leaks into urine
    • 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
    • decreased serum haptoglobin
      • destruction of RBC in blood vessel will cause hemoglobin to pass directly into the blood
      • first response of the body is to bind a scavenger molecule called haptoglobin to it
      • haptoglobin takes hemoglobin to the spleen to be reprocessed
      • free haptoglobin levels will decrease when binding to hemoglobin in serum
41
Q

What is the cause of heriditary spherocytosis?

A
  • inherited defect of RBC cytoskeleton-membrane tethering proteins
    • most commonly involves ankyrin, spectrin or band 3
    • in normal RBCs, the cytoskeleton which maintains the shape of the cell is tethered to the cell membrane by tethering molecules
    • in spherocytes, the tethering molecules are disrupted
    • results in little blebs of membrane coming off the RBC
    • the blebs are removed by the spleen when the blood cell moves through the spleen
    • over time, as you lose membrane, you lose the ability to form the biconcave shape and the RBC becomes spherocytic (circular)
    • spherocytes are less able to manuever through splenic sinusoids and are consumed by spelinc macrophages, resulting in anemia
      • the spherocytes work fine but eventually the cells won’t be able to get through the spleen and are destroyed by macrophages
42
Q

What are the clinical and lab finding of spherocytosis?

A
  • Spherocytes with loss of central pallor
  • Increase RDW and increase mean corpuscular hemoglobin concentration
    • cells gets smaller so hemoglobin gets more concentrated in the cell
  • Splenomegaly
    • macrophages of the spleen undergo hypertropy as they eat RBCs
  • Jaundice with unconjugated bilirubin and increased risk for bilirubin gallstones
  • Increased risk for aplastic crisis with parovirus B19 infection of erythroid precursors
    • only have a few RBCs so shutting down production b/c of virus is bad
43
Q

How is hereditary spherocytosis diagnosed?

A
  • osmotic fragility trst which reveals increased spherocyte fragility in hypotonic solution
    • normal cell can take on water and won’t burst in hypotonic solution
    • Spherocyte will
44
Q

What is the treatment for Hereditary Spherocytosis?

A
  • Splenectomy
    • anemia resolves but spherocytes persist and Howell Jolly bodies (fragments of nuclear material in RBCS emerge on blood smear)
      • It is the job of the spleen to remove fragments of extra nuclear material from the RBC but spleen can’t do that since spleen isn’t there
45
Q

What is the cause of Sickle Cell Anemia?

A
  • autosomal recessive mutation of B chain of hemoglobin
    • a single amino acid change replaces normal glutamic acid with valine
  • Sickle Cell disease arises when two abnormal B genes are present results into >90% HbS in RBCs
  • Sickle Cell trait is the presence of one mutated and one normal B chain resulting in RBC <50% HbS
    • generally asymptomatic with no anemia
    • RBCS with <50% do not sickle except in the renal medulla
46
Q

Pathophysiology of Sickle Cell

A
  • HbS polymerizes when deoxygenated (placed under stress)
  • Polymers aggregate into needle-like structures 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
  • Cells continuously sickle and de-sickle when passing through the microcirculation, resulting in complications related to RBC membrane damage
    • Extravascular hemolysis: reticuloendothelial system removes RBCs with damaged membranes leading to anemia, jaundice with unconjugated hyperbilirubinemia and increased risk of bilirubin gallstones
    • Intravascular hemolysis: RBCs with damaged membranes dehydrate leading to hemolysis with decreased haptoglobin and target cells on blood smear
    • Massive Erythroid hyperplasia ensues resulting in:
      • Expansion of hematopoiesis into the skull (crewcut appearance on x-ray) and facial bones (chipmunk face)
      • Extramedullary hematopiesis with hepatomegaly
      • Risk of aplastic crisis with parovirus B19 infection of erythroid precursors
47
Q

What are the effects of extensive sickling?

A
  • leads to complications of vaso-occlusion
  • Dactylitis: swollen hands and feet due to vaso-occlusive infarcts in bones: common in infants
  • Autosplenectomy: shrunken, fibrotic spleen
    • at risk for increased infections from encapsulated organisms such as Strep pneumo and Haemophilus influenzae
    • most common cause of death in children
    • affected children should be vaccinated by 5 years of age
    • increased risk of Salmonella paratyphi osteomyelitis
    • Howell-Jolly bodies on blood smear
      • no spleen so cells with nuclear material will not be removed
  • Acute Chest Syndrome: vaso-occlusion in pulmonary microcirculation
    • presents with chest pain, SOB, and lung infiltrates
    • often precipitated by pneumonia
    • most common cause of death in adult patients
  • Pain crisis: other bones or organs
  • Renal Papillary necrosis: results in gross hematuria and proteinuria
48
Q

Sickle Cell Anemia Lab Findings

A
  • Sickle cells and target cells are seen on blood smear in sickle cell disease but not in sickle cell trait
  • Metabisfulfite screen causes cells with any amount of HbS to sick: positive in both disease and trait
  • Hb electrophoresis confirms the presence and amount of HbS
49
Q

What is Hemoglobin C?

A
  • Autosomal recessive mutation in Beta chain of hemoglobin
    • normal glutamic acid is replaced by lysine
    • less common than sickle cell
  • Presents with mild anemia due to extravascular hemolysis
  • Characteristic HbC cystals are seen in RBCs on blood smear
50
Q

What is the cause of Paroxysmal Nocturnal Hemoglobinuria?

A
  • acquired defect in PIGA gene affecting myeloid stem cells
  • Results in glycosylphosphatidylinositol (GPI): renders cells susceptible to destruction by complement
    • RBCs protect themselves from compliment by having DAF and MIRL on their surface
    • these two molecules inactivate compliment
    • DAF and MIRL are conencted to the RBC by an anchoring protein: GPI
    • in PNH have acquired defect so GPI is not present on cells so suceceptible to complement-mediated damage
51
Q

What are the clinical/lab finds of Paroxysmal Nocturnal Hemoglobinuria?

A
  • Intravascular hemolysis occurs episodically: especially at night
    • mild respiratory acidosis develops with shallow breathing during sleep and activates compliment
    • RBCs, WBCs and platelets are lysed
  • Intravascular hemolysis leads to hemoglobinemia and hemoglobinuria especially in the morning
  • Sucrose test is used to screen for the disease: confirmatory test is the acidified serum test or flow cytometry to detect lack of CD55 (DAF) on blood cells
    • CD55 uses GPI as a linker molecule
  • Main causes of death is thrombosis of the hepatic, portal or cerebral veins
    • destroyed platelets release cytoplasmic contents into circulation, inducing thrombosis
  • Complications include iron deficiency anemia (due to chronic loss of hemoglobin in the urine) and acute myeloid leukemia if they get more mutations in the stem cell
52
Q

How does G6PD effect RBCs?

A
  • RBCs live in an environment of oxidative stress
  • to protect themselves, they use glutathione which takes free radicals from molecules such as H2O2 and neutralizes them
  • For glutathione to continue working, the oxidatized glutathione needs to be reduced back
  • NADPH (produced from G6PD) does this
  • no G6PD = no NADPH
  • No NADPH = no ability to regenerate reduced glutatione
  • Have increased oxidative damage to RBCs
53
Q

What are the two variants of G6PD deficiency?

A

X-linked recessive disorder

  1. African variant
    • mildy reduced half-life of G6PD leading to mild intravascular hemolysis with oxidative stress
    • mildly reduced half life = only the older cells will be destroyed
  2. Mediterranean Variant
    • Markedly reduced half-life of G6PD leading to marked intravascular hemolysis with oxidative stress
    • markedly reduced half life = G6PD is absent in RBCs signifcantly earlier than they should be
54
Q

What are the clinical/lab findings in G6PD deficiency?

A
  • Oxidative stress precipates Hb as Heinz bodies
    • causes of oxidative stress include infections, drugs, and fava beans
    • Heinz bodies are removed from RBCs by splenic macrophages, resulting in bite cells
    • leads to predominantely intravascular hemolysis
  • presents with hemoglobinuria and back pain hours after exposure to oxidative stress
  • Heinz prep is used to screen for disease
  • Enzyme studies confirm deficiency: performed weeks after hemolytic episode resolves b/c all the alive cells during the attack still have G6PD
55
Q

What is Immune Hemolytic Anemia?

A
  • antibody mediated (IgG or IgM) destruction of RBCs
56
Q

IgG Immune Hemolytic Anemia

A
  • IgG mediated disease usually involves extravascular hemolysis
  • IgG binds RBCs in the relatively warm temperature of the central body
    • membrane of antibody-coated RBC is consumed by spenic macrophages, resulting in formation of spherocytes: losing membrane so cell becomes spherocytic
  • Associated with Lupus, CLL and certain drugs
    • drugs may attach to RBC membrane with subsequent binding of antibody to drug-membrane complex
    • Drug may induce production of autoantibodies that bind self antigens on RBC
  • Treatment involves cessation of the offending drug, steroids, IVIG (spleen eats IVIG instead of the RBCs), and if necessary, splenectomy
57
Q

IgM Immune Hemolytic Anemia

A
  • IgM-mediated disease usually involves intravascular hemolysis
    • IgM binds RBCs and fixes complement in the relatively cold temperature of the extremities (cold agglutinins)
    • Associated with Mycoplasma pneumonie and infectious mono
58
Q

How is Immune Hemolytic Anemia diagnosed?

A

Direct Coombs test

59
Q

What is Microangiopathic Hemolytic Anemia?

A
  • intravascular hemolysis that results from vascular pathology
    • in the small vessel, get some sort of thrombis that blocks the blood vessel partially
    • causes sheering of RBCs that are trying to go through
    • causes formation of schistocytes
    • Iron deficiency anemia occurs with chronic hemolysis
  • Occurs with microthrombi (TTP-HUS, DIC) prosthetic heart valves, and aortic stenosis
60
Q

What is Malaria?

A
  • Infection of RBCs and liver with Plasmodium: transmitted by female Anopheles mosquito
  • RBCs rupture as a part of the Plasmodium life cycle, results 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
61
Q

How does Parvovirus B19 cause anemia?

A
  • infects progenitor red cells and temporarily halts erythropoiesis leading to significant anemia in the setting of preexisting marrow stress (ex. sickle cell)
  • treatment is supportive
62
Q

What is aplastic anemia?

A
  • Damage to hematopoietic stem cells resulting in pancytopenia (anemia, thrombocytopenia and leukopenia) with low retikulocyte count
  • etiologies include drugs or chemicals, viral infections and autoimmune damage
  • biopsy reveals an empty, fatty marrow
  • treatment includes cessation of any causative drugs and supportive care with transfusions and marrow-stimulating factors
    • Immunosuppression may help as some idiopathic cases are due to abnormal T cell activation with release of cytokines
    • May require bone marrow transplant
63
Q

Myelopthisic Process

A
  • pathologic process (ex. metastatic cancer) that replaces bone marrow
  • hematopoiesis is impaired resulting in pancytopenia

Heme/Onc Pathoma (10 decks)

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