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4_5_6_Hematology Flashcards

1
Q

What is anemia? (in terms of physiology and in terms of lab values)

A

Reduction in circulating RBC mass

Males = Hb <12.5 g/dL

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2
Q

Classic signs and symptoms of hypoxia (secondary to anemia)

A 
Weakness
Fatigue
Dyspnea
Pale conjunctiva and skin (Pallor)
Headache, lightheadedness
Angina (esp. w/ preexisting CAD)
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3
Q

What metrics are used as surrogates to measure RBC mass?

A

Hb (Hemoglobin)
Hct (Hematocrit - %blood volume composed of RBC)
RBC count

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4
Q

Why are Hb, Hct and RBC count considered surrogate measures of RBC mass?

A

They are concentration dependent.

You could infuse saline and decrease all of their values without changing the RBC Mass.

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5
Q

What are the MCV cutoffs for microcytic, normocytic and macrocytic anemias?

A

Microcytic 100

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6
Q

What is the underlying cause of ALL microcytic anemias?

A

Decreased hemoglobin production

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7
Q

Why does decreased hemoglobin production lead to microcytic anemia?

A

RBC progenitor cells are large and divide multiple times to make smaller mature cells.
Decreased hemoglobin forces the cells to make one extra division to maintain Hb concentration, thus smaller cells, thus microcytic.

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8
Q

What are the four microcytic anemias?

A 
Insufficient Fe (iron deficiency, anemia of chronic disease)
Insufficient protoporphyrin (Sideroblastic anemia)
Insufficient globin (Thalassemia)
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9
Q

What is the most common type of anemia?

A

Iron deficiency anemia.

1/3 of world’ population.

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10
Q

What are our two sources of dietary iron?

A

Heme-iron = meat derived

Non-heme Iron = vegetable derived

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11
Q

Where is iron absorbed in the gut?

A

Duodenum

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12
Q

Describe the physiology of how Iron is absorbed in the gut

A

1) Enterocytes have a special transporter for either heme or non-heme iron that moves it into the cell. But heme iron is more readily absorbed.
2) Ferroportin transports iron across cell membrane into blood
3) Transferrin transport iron in the blood and delivers it to liver and bone marrow macrophages for storage

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13
Q

How is iron stored in the body?

A

Bound to ferritin. Prevents iron from forming free radicals via the Fenton Reaction

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14
Q

What are the laboratory measurements of iron status?

A

Serum Iron
Total Iron-binding capacity
% saturation
Serum ferritin

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15
Q

What is Total Iron Binding Capacity?

A

Measures total levels of transferrin (regardless of whether iron is bound to it)

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16
Q

What % saturation? What should this value normally be?

A

Percentage of transferrin molecules that are bound by iron.

Know that this is usually 1/3 (33%)

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17
Q

What does serum ferritin tell you?

A

Reflects iron stores in macrophages adn the liver

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18
Q

What are the two ways you can get iron deficiency?

A

Dietary deficiency

Blood loss

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19
Q

What are the most common ways these age groups develop Iron deficeincy?

1) Infants
2) Children
3) adults
4) Eldery

A 
Infants = breast feeding (breast milk is low in iron)
Children = poor diet
ADults = peptic ulcer disease in men. menorrhagia or pregnancy in females
Elderly = colon polyps/carcinoma in west; hookworm in developing world
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20
Q

How does gastrectomy lead to iron deficiency?

A

Acid normally aids Iron absorption by maintaining Fe2+ state (which is easier absorbed)
Gastrectomy reduces acid secretion, so less efficient Fe absorption

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21
Q

Describe the stages of iron deficiency. (Which sources of iron in your body are used up 1st, 2nd etc..?)

A

1) Storage iron is depleted first = low ferritin; high TIBC
2) Serum iron depleted 2nd = low serum Fe; low % saturation
3) Normocytic anemia - marrow makes fewer RBCs that are normal sized
4) Microcytic, hypochromic anemia - smaller and fewer RBCs as Fe-deficeincy worsens

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22
Q

What is the relationship between TIBC and Ferritin

A

Always the opposite. When ferritin goes down, TIBC goes up.
IT’s as if when we run low on Fe stores, the body sends out transferring to scavenge for Fe wherever it can, thus increasing TIBC.

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23
Q

Clinical features of iron deficiency

A

Anemia
Koilonychia (spoon shaped nails)
Pica - chewing on abnromal things for iron like dirt

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24
Q

Laboratory for microcytic anemias

A

Blood smear = Microcytic, hypochromic RBCs with increased RDW
Serology = low ferrin, high TIBC, low serum Fe, low % saturation
High Free Erythrocyte Protoporphyrin (FEP)

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25
Q

What is Free Erythrocyte Protoporphyrin?

A

Protoporphyrin floating in the blood without a heme.
Elevated in Fe-deficiency anemias because theres no defect in protoporphyrin synthesis, its just the last step of inserting an Fe can’t be done.

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26
Q

What is RDW?

A

RBC Distribution Width - How variable is the size of RBCs on a blood smear.

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27
Q

Treatment of Fe-deficeincy anemia

A

Treat underlying cause of Iron deficeincy

Iron supplementation

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28
Q

What is Plummer Vinson Syndrome?

A

Iron deficeincy anemia with esophageal web and atrophic glossitis
Esophageal webs are highly associated with this syndrome, which also has Fe-deficiency anemia

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29
Q

What is anemia of chronic disease?

A

Anemia associated with chronic INFLAMMATION or cancer.

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30
Q

Why does anemia of chronic disease cause a microcytic anemia?

A

Chronic disease produces acute inflammatory reactants in liver (including hepcidin)
Hepcidin sequesters iron in storage by 1) Keeping Fe stored in macrophages 2) suppressing EPO
Decreased Fe = Decreased Heme = Decreased Hb = microcytic anemia

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31
Q

Why does the body release sequester Iron in inflammatory states?

A

Any inflammation and the body thinks its a bacterial infection.
Fe is a critical nutrient for bacteria.
Sequestering Fe is a way to kill the bacteria

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32
Q

Laboratory findings of Anemia of Chronic disease.

A

Serology: high ferritin; low TIBC; low Serum Fe; low % saturation
High Free Erythrocyte PRotoporphyrin

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33
Q

Treatment of Anemia of Chronic Disease

A

Address underlying cause

Exogenous EPO is useful in some patients esp. those w/ cancer.

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34
Q

What is sideroblastic anemia?

A

Anemia due to defective protoporphyrin synthesis

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35
Q

Why does sideroblastic anemia cause a microcytic anemia?

A

Decreased protoporphyrin = decreased heme = decreased hemoglobin = microcytic anemia

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36
Q

What are the three key reactions in protoporphyrin synthesis? Where in the cell do they occur?

A

Cytosol rxns:
1) Succinyl Coa to ALA (using ALAS w/ B6 cofactor)
2) ALA to Prophobilinogen (using ALAD)
Prophobilinogen -> Protoporphyrin (magic! many unimportant steps)
Mitochondrial rxns:
3) Protoporphyrin to heme (using Ferrochelatase w/ Fe)

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37
Q

What is the histologic appearance of RBCs in sideroblastic anemia? explain the biology behind this appearance

A

Ringed sideroblast = Erythroid precursors with a ring of iron-laden mitochondria around the nucleus.

Fe enters mitochondira to be loaded onto protoporphyrin but a defect in heme enzymes synthesis means Fe gets trapped with nowhere to go.

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38
Q

Causes of sideroblastic anemia

A

Congenital or aquired
Congenital = usually ALAS defect
Acquired
- alcoholism (mitochondrial poison)
- Lead poisoning (inhibits ALAD and ferrochelatase)
- B6 deficeincy (most commonly isoniazid (TB drug) side effect)

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39
Q

Laboratory findings in Sideroblastic Anemia

A

high ferritin; low TIBC

high serum Fe; High % saturation

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40
Q

What is a Thalassemia

A

Anemia due to decreased SYNTHESIS of globin chains of hemoglobin due to an inherited mutation.

Different from mutation in globin chain like in sickle cell anemia.

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41
Q

Why does thalassemia cause a microcytic anemia?

A

Low globin = low hemoglobin = microcytic anemia

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42
Q

What are the different types of hemoglobin?

A 
HbF = fetal =alpha2gamma2
HbA = alpha2beta2
HbA2 = alpha2delta2
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43
Q

What are alpha-thalassemias?

A

Usually deletion of an alpha-globin gene (we have 4 alleles total)

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44
Q

What happens with one alpha-globin gene deletion

A

asymptomatic alpha thalassemia

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45
Q

What happens with two alpha-globin gene deletions?

A

mild anemia with increased RBC count.
If both genes are on the same chromosome = CIS deletion. more common in asians. increased risk of severe thalassemia in offspring.

If genes are on different chromosomes = Trans deletion. more common in africans/african americans.

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46
Q

What happens with three alpha-globin gene deletions?

A

Severe anemia.
Beta globins start forming tetramers since there aren’t enough alpha-globin dimers (called HbH).
No problem in utero. No ß-globin yet. just one alpha globin gene is Sufficient for HbF

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47
Q

What happens when all four alpha-globin genes are deleted?

A

Lethal in utero. aka Hydrops Fetalis

Gamma globin tetramers form (HbBarts) and damages RBCs.

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48
Q

What is Beta THalassemia?

A 
Gene mutation (usually point mutation in promoter or splicing sight) common in African and MEditerraneans
Mutation results in absent (ß0 = beta null) or diminished (ß+) production of beta globin chain. 
We have two beta-globin alleles to work with.
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49
Q

WHat is Beta Thalassemia Minor

A

B/B+ = one normal beta globin with one beta positive

Mildest form of disease and usually asymptomatic with increase RBC count

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50
Q

What are the laboratory findings of beta thalassemia minor?

A

Blood smear = microcytic, hypochromic RBCs and target cells

Electrophoresis = slightly decreased HbA with increased HbA2 and HbF

51
Q

What is Beta Thalassemia Major

A

B0/B0 = most severe form of disease.
SEvere anemia a few month safter birth.
No disease in utero. HbF from birth is temporarily protective.

52
Q

Describe the pathophysiology of ß-thalassemia major

A

alpha tetramers aggregate and damage RBCs
results in ineffective erythropoiesis (premature death of RBC) and extravascular hemolysis (removal of ciculating RBCs by spleen)

53
Q

What are the physical findings of ß-thalassemia major?

A

Massive Erythroid hyperplasia ensures resulting in:

1) expansion of hematopoiesis into skull (crewcut appearance on x-ray) and face (chipmunk face)
2) Extramedullary hematopoiesis with hepatosplenomegaly
3) Risk of aplastic crisis with PArvo B19 infection (infection of erythroid precursors)

54
Q

Therapy for ß-thalassemia major

A

Chronic transfusions are often necessary - can lead to secondary hemochromatosis

55
Q

LAboratory findings in ß-thalassemia major

A

blood smear = microcytic hypochromic RBCs with target cells and nucleated RBCs. (nucleated RBCs escape when made in extramedullary locations)

Electrophoresis shows little or no HbA with increased HbA2 and HbF

56
Q

Explain what target cells are.

A

Excess membrane in RBC or reduced hemoglobin means the cell isn’t full enough to maintain biconcave shape.
Small bleb of membrane in the middle pops up allowing some Hb to stay in the middle, creating target appearance.

57
Q

What is megaloblastic Anemia? What changes do you see associated with it?

A

Any macrocytic anemia involving Folate and B12 deficiency. Both needed for DNA precursors, thus rapidly dividing cells become big from not being able to divide. 1) Enlargement of RBC precursors 2) Hypersegmented neutrophils (>5 lobes) 3) Enlargement of other rapidly dividing cells (like epithelium of intestine)

58
Q

Explain the role of folate and B12 in the synthesis of DNA precursors:

A
  1. Folate is methylated, circulating as methyl THF in the body and needs to be demethylated in order to participate in the synthesis of DNA precursors. 2. The methyl group is transferred to vitamin B12. 3. Vitamin B12 then transfers it to homocysteine, making methionine.;
59
Q

What causes macrocytic anemia without megaloblastic change?

A
  1. Alcoholism2. Liver Disease3. Drugs;
60
Q

Compare the source of folate and vitamin B12 in the diet and their sites of absorption:

A

Folate is obtained from green vegetables and some fruits and is absorbed in the jejunum. Vitamin B12 is complex to animal-derived proteins and is absorbed in the ileum.;

61
Q

Why does deficiency of folate develop within a shorter time span than vitamin B12 deficiency, which often takes years?

A

Body stores of folate are minimal while there are large hepatic stores of vitamin B12.;

62
Q

What are the causes of folate deficiency?

A
  1. Poor diet (alcoholics and elderly)2. Increased demand (pregnant, cancer, hemolytic anemia)3. Folate antagonists (methotrexate, inhibits dihydrofolate reductase);
63
Q

What are the clinical and laboratory findings that are common to both folate deficiency and vitamin B12 deficiency? What findings differ and can be used to differentiate between the two?

A

Same – macrocytic RBCs and hypersegmented neutrophils; glossitis;increased serum homocysteine (increased risk of thrombosis)
Folate deficiency: reduced serum folate and normal methymalonic acid
B12 deficiency: Elevated methylmalonic acid (conversion to succinyl coA requires B12), reduced serum B12,;

64
Q

Why is subacute combined degeneration of the spinal cord seen in vitamin B12 deficiency?

A

Vitamin B12 is a cofactor for the conversion of methylmalonic acid to succinyl CoA (important for fatty acid metabolism)Deficiency of B12 results in increased levels of methylmalonic acid, which impairs spinal cord myelinzation, resulting in poor proprioception and vibratory sensation (DCML) and spastic paresis (Lateral cortical spinal tract);

65
Q

How does Vitamin B12 get into the body? Begin from physiologic processes in the mouth all the way to absorption.

A
  1. Salivary gland enzymes such as amylase liberate vitamin B12, which is then bound by R-binder also produced by the salivary grand) and is carried to the stomach.2. Pancreatic proteases in the duodenum detach vitamin B12 from R-binder.3. Vitamin B12 binds intrinsic factor (made in stomach by gastric parietal cells) in the small bowel – this complex of B12 and intrinsic factor is absorbed in the ileum.;
66
Q

Most common cause of Vitamin B12 deficiency?

A

Pernicious anemia – autoimmune destruction of parietal cells in stomach that leads to deficiency of intrinsic factor.;

67
Q

Besides pernicious anemia, what else has been associated with Vitamin B12 deficiency?

A
  1. Pancreatic insufficiency (as pancreas produces enzymes that cleave B12 from R-binder)2. Damage to terminal ileum (e.g. Crohn’s disease, Diphyllobothrium latum - tapeworm)3. Dietary deficiency in vegans – otherwise rare.;
68
Q

What is the main question in order to determine the cause of NORMOCYTIC anemia? What lab test can answer this question?

A

Whether it is due to peripheral destruction of RBC’s or underproduction.Reticulocyte count helps to distinguish between these two etiologies by telling us how active RBC production is in the marrow;

69
Q

What are reticulocytes? How can they be identified on a blood smear? What is the “normal reticulocyte count?

A

Reticulocytes = Young RBC’s released from the bone marrowIdentified as larger cells with bluish cytoplasm due to residual RNA. Normal amount = 1-2%, which is how many RBCs die every day and need a reticulocyte to replace it.

70
Q

A properly functioning marrow responds to anemia by increasing the reticulocyte count (RC) to >3% – however it can be falsely elevated in anemia – Explain. What is the correction?

A

RC is measured as a percentage of total RBC’s – with a decrease in total RBC’s falsely elevating the percentage of reticulocytes.
Corrected RC = Hct/45 *RC

Corrected RC >3% = peripheral destruction
Corrected RC <3% = underproduction

71
Q

Both extravascular and intravascular hemolysis result in anemia with a high corrected RC - True or False?

A

True – not an issue with production but peripheral destruction.;

72
Q

What is the difference between extravascular and intravascular hemolysis?

A

Extravascular hemolysis involves RBC destruction by the reticuloendothelial system (i.e. macrophages of the spleen, liver, and lymph nodes)Intravascular hemolysis involves destruction within vessels.;

73
Q

In Extravascular Hemolysis (EH) Macrophages consume RBC’s and break down hemoglobin. What happens to the Hb components?

A
  1. Globin is brokem down into amino acids2. Heme is broken down into iron, which is recycled and protoporphyrin.Protoporphyrin is broken down into unconjugated bilirubin, which is bound to serum albumin and delivered to the liver for conjugation and excretion in bile.;
74
Q

What are the clinical and laboratory findings of EXTRAVASCULAR hemolysis?

A
  1. Anemia with splenomegaly 2. Jaundice due to unconjugated bilirubin in serum as liver has fixed capacity 3. Increased risk for bilirubin gallstones 4. Marrow Hyperplasia with corrected reticulocyte count >3%;
75
Q

What are the clinical and laboratory findings of INTRAVASCULAR hemolysis?

A
  1. Hemoglobinemia 2. Hemoglobinuria 3. Hemosiderinuria (renal tubular cells pick up some of the Hb that is filtered into the urine and break it down into iron, which accumulates as hemosiderin;tubular cells are eventually shed resulting in hemosiderinuria) 4. Decreased serum haptoglobin (initially);
76
Q

What is haptoglobin?

A

Binds free hemoglobin and takes it to the spleen in order to conserve iron and prevent damage. Often decreased during intravascular hemolysis.;

77
Q

Spherocytosis in an inherited defect of RBC cytoskeleton-membrane tethering proteins. What are the most commonly involved proteins?

A
  1. Spectrin 2. Ankyrin 3. Band 31;
78
Q

Why do RBC’s become spheres in spherocytosis? How does this result in anemia?

A

Membrane blebs are formed and lost over time resulting in the loss of the disc shaped.Spherocytes are less able to maneuver through the splenic sinusoids and are consumed by splenic macrophages, resulting in anemia.;

79
Q

What are the clinical and laboratory findings associated with spherocytosis?

A
  1. Spherocytes with a loss of central pallor 2. Increased RDW and MCHC (mean corpuscular hemoglobin concentration) 3. Splenomegaly + Jaundice with unconjugated bilirubin + bilirubin gallstones 4. Increased risk for aplastic crisis with parvovirus B19 (which infects erythroid precursors)
80
Q

How does one diagnose hereditary spherocytosis?

A

Osmotic fragility test. Dunk in hypotonic solution. spherocytes explode bec/ not enough membrane to accommodate influx of fluid. normal cells resistant.

81
Q

What is the treatment for spherocytosis?

A

Splenectomy –> Anemia resolves but spherocytes persist and howell jolly bodies (fragments of nuclear material in RBCs) emerge on blood smear;

82
Q

Sickle cell anemia is associated with an autosomal recessive mutation causing a single amino acid change in the Hb chain – what is the change?

A

Glutamic acid (hydrophilic) to valine (hydrophobic);

83
Q

What percentage of individuals of African descent carry the sickle cell anemia gene?

A

10% – due to protective role against falciparum malaria;

84
Q

Sickle cell disease arises when two abnormal ___ genes are present – resulting in >90% of Hb___ in RBCs:

A

Beta; HbS

85
Q

How does HbS result in the pathology seen in sickle cell anemia?

A

HbS polymerize when deoxygenated – aggregating into needle-like structures, resulting in sickle cell.;

86
Q

What factors can induce sickling?

A
  1. Hypoxemia 2. dehydration 3. acidosis
87
Q

High levels of HbF are protective for the first few months of life in sickle cell anemia patient. What treatment can maintain these high levels of HbF?

A

Hydroxyurea;

88
Q

Explain how both extravascular and intravascular hemolysis play a role in sickle cell anemia:

A

Cells continuously sickle and de-sickle while passing through the microcirculation, resulting in complications related to RBC membrane damage. Extravascular hemolysis occurs as the reticuloendothelial system removes damaged RBCs.
Intravascular hemolysis occurs as RBCs with damaged membranes dehydrate, eventually leading to hemolysis (not the predominant method of hemolysis though);

89
Q

Sickle Cell Anemia is associated with massive erythroid hyperplasia and risk of aplastic crisis with B19 virus - True or False?

A

True;

90
Q

What are the complications of vaso-occlusion associated with irreversible sickling?

A
  1. Dactylitis – swollen hands and feet due to infarcts in bones (common in infants) 2. Autosplectomy – i.e. shrunken fibrotic spleen 3. Acute chest syndrome (due to vaso-occlusion in pulmonary circulation) 4. Pain Crisis 5. Renal Papillary Necrosis (gross hematuria and proteinuria);
91
Q

What are consequences of autosplenectomy often seen in sickle cell anemia?

A
  1. Increased risk of infection with encapsulated organisms such as Streptococcus pneumoniae and haemophilus influenza (most common cause of death in affected children – require vaccination)2. Increased risk of salmonella paratyphi osteomyelitis3. Howell Jolly Bodies on blood smear (nucleus not removed);
92
Q

Describe the presentation of acute chest syndrome in sickle cell anemia patients?

A

Present with chest pain, shortness of breath and lung infiltrates;often precipitated by Pneumonia - vasodilation of pulmonary capillary beds causes slow transit time, increased sickling and pain int he lungs from sickles. most common cause of death in adult patients*;

93
Q

What is sickle cell trait?

A

The presence of one mutated and one normal Beta chain – resulting in <50% HbS in RBCs (HbA is slightly more efficiently produced than HbS);

94
Q

RBCs with <50% HbS do not sickle such that sickle trait individuals are generally asymptomatic and present with no anemia – True or False?

A

Mostly true — except that these RBC’s may sickle in the renal medulla as a result of the extreme hypoxia and hypertonicity of the medulla. This causes microinfarcts leading to microscopic hematuria and eventual decrease in the ability to concentrate urine.;

95
Q

Diagnosis of both sickle cell disease and sickle cell trait can be done on a blood smear - True or False?

A

False — while sickle cells and target cells are seen on blood smear in sickle cell DISEASE – they do not sickle in TRAIT.;

96
Q

Given that blood smear is ineffective at detecting sickle cell trait, what tests can identify both sickle cell disease and trait?

A

Metabisulfite screen – causes cells with any amount of HbS to sickle
Additionally, Hb electrophoressis confirms the presence and amount of HbS;

97
Q

Compare and contrast values seen on Hb electrophoresis in sickle cell disease and trait:

A

Disease: 90% HbS, 8% HbF, 2% HbA2, NO HbATrait: 55% HbA, 43% HbS, 2% HbA2;

98
Q

What is hemoglobin C? Why is it associated with anemia? How can you identify it on blood smear?

A

Caused by an autosomal recessive mutation in Beta chains of hemoglobin that switches glutamic acid to lysine (instead of valine like in SCA)8. Less common than sickle cell disease, it presents with mild anemia due to extravascular hemolysis. Characteristic HbC crystals are seen in RBCs on blood smear.;

99
Q

What is the defect with Paroxysmal Nocturnal Hemoglobinuria (PNH)? What does complement have to do with it?

A

Results from an acquired defect in myeloid stem cells resulting in absent GPI, which normally anchors DAF and MIRL. DAF and MIRL protects against complement-mediated damage by inhibiting C3 convertase.Absence of GPI leads to absence of DAF, rendering cells susceptible to complemented mediated damage.;

100
Q

Explain the “PN” part of PNH (paroxysmal nocturnal hemoglobinuria):
What are clinical signs of PNH?

A

Mild respiratory acidosis develops with shallow breathing at night during sleep and acidosis activates complement. Complement causes intravascular hemolysis of the RBCs which lack DAF and MIRL to protect against lysis. You wake up with dark pee (hemoglobinuria) after a night of acidosis.

Signs: Hemoglobinemia, hemoglobinuria, hemosiderinuria.

101
Q

How can you screen for PNH? How do you confirm the diagnosis?

A

Sucrose test can be used to screen for the disease as it activates complement. Confirmatory testing: Acidified serum test (acidemia triggers complement) or flow cytometry to detect lack of CD55 (DAF) on blood cells.;

102
Q

What is the main cause of death in PNH patients? Describe the pathophysiology.

A

Hepatic, portal or cerebral vein thrombosis.
Inability of all blood cells to defend against complement (not just RBCs)
Destroyed platelets release cytoplasmic contents into circulation, inducing thrombosis;

103
Q

What are the two complications of PNH?

A
  1. Iron deficiency anemia (due to chronic loss of Hb in the urine)2. Acute myeloid leukemia (AML) in 10% of patients;
104
Q

Why does the reduced half-life of G6PD in G6PD deficiency (x-linked recessive) lead to intravascular hemolysis?

A

RBC’s succumb to oxidative damage.
Lack of G6PD = unable to reduce NADPH, which reduces glutathione. Glutathione is no longer available to neutralized ROS like H2O2.
Oxidative stress –> Intravascular hemolysis.

105
Q

What are the two variants of G6PD deficiency? Which is more severe.

A

African variant – mildly reduced half-life of G6PD resulting in 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.;

106
Q

Why do you se bite cells in G6PD deficiency?

A

Oxidative stress precipitates Hb as Heinz bodies – causes of such stress include infections, drugs and fava beans.Heinz bodies are removed from RBC’s by splenic macrophages resulting in the “bite cell”; NOT the predominant methdo of hemolysis though. the cell is still alive its just a bite cell

107
Q

Why do patients with G6PD deficiency present with back pain?

A

G6PD def. leads to intravascular hemolysis, resulting in hemoglobinemia/uria —> Hb is nephrotoxic.;

108
Q

How do you screen for G6PD deficiency? What is a limitation of this screen?

A

Heinz preparation is used to screen for G6PD deficiency (precipitated Hb can only be seen with a special Heinz stain) – must be performed weeks after hemolytic episode resolves because at the time, all cells lacking the enzyme are dead, resulting in a false-negative.;

109
Q

How does IgG mediated immune hemolytic anemia (IHA) differ from that mediated by IgM?

A

IgG = extravascular IgM = intravascular;

110
Q

How does IgG IHA work?

A
  1. IgG binds RBCs in the relatively warm temperature of the central body; 2. Membrane of antibody coated RBC is consumed by splenic macrophages –> resulting in spherocytes;
111
Q

What is IgG IHA associated with? What is the most common cause?

A
  1. SLE (most common cause) 2. CLL 3. Drugs (penicillin and cephalosporin);
112
Q

How can penicillin and methyldopa cause an IgG mediated hemolytic anemia? Explain.

A

Penicillin may attach to RBC membrane with subsequent binding of antibody to drug-membrane complex.
Methyldopa induces the production of autoantibodies that bind the self-antigens on RBCs.;

113
Q

List treatment options for IgG IHA:

A
  1. Cessation of offending drug (e.g. cephalosporin, penicillin, methyldopa) 2. Steroids (slow production of antibody) 3. IVIG (splenic macrophages eat it instead)4. Splenectomy (eliminate source of antibody/destruction);
114
Q

How does IgM mediated hemolytic anemia work? What infectious agents is it associated with?

A

IgM binds RBCs and fixes complement in the relatively cold temperature of the extremities –> MAC complex mediated destruction

Associated with 2 bugs: Mycoplasma pneumoniae and Infectious mononucleosis;

115
Q

Both the direct and indirect coombs test can be used to diagnose IHA – how do they work and which one is preferred?

A

Direct coombs test confirms the presence of antibody-coated RBCs. Anti-IgG is added to patient RBC’s – agglutination occurs if the RBCs are already coated with antibody – this is the most important test for IHAIndirect coombs test confirms the present of antibodies in patient serum. Anti-IgG and test RBC’s are mixed with patient serum; agglutination occurs if serum antibodies are present.;

116
Q

What is microangiopathic hemolytic anemia? What are some common causes? What do you see on blood smear?

A

Intravascular hemolysis that results from vascular pathology – RBCs are destroyed as they pass through the microcirculation and get sheared by vascular thrombi. Associated with:(1) TTP (platelet thrombi due to lack of ADAMST13 (2) HUS (toxin produced by strain of E. Coli)(3) DIC (platelet fibrin thrombi)(4) HELLP(5) Prosthetic heart valves + aortic stenosis (crush RBC’s)
Microthrombi produce schitocytes on blood smear.;

117
Q

Infection of RBCs and liver by what microbe that is transmitted by the female anopheles mosquito?

A

Plasmodium (malaria);

118
Q

Why causes the intravascular hemolysis in malarial infection? Is there any extravascular hemolysis?

A

RBC’s rupture as a part of the Plasmodium life cycle, resulting in intravascular hemolysis and cyclical fever. P. Falciparum (daily fever) and P. Vivax/Ovale (fever every other day). Spleen also consumes some infected RBC’s – resulting in mild extravascular hemolysis with splenomegaly.;

119
Q

A low corrected RC is indicative of what cause of anemia?

A

Decreased production of RBC’s by bone marrow;

120
Q

What etiologies are associated with anemia due to underproduction?

A
  1. Microcytic and Macrocytic anemia 2. Renal failure (decreased production of EPO) 3. Damage to bone marrow precursors (may result in anemia or pancytopenia);
121
Q

How can parvovirus B19 cause anemia?

A

This virus infects progenitor red cells and temporarily halts erythropoiesis and can lead to significant anemia in the setting PRE-EXISTING marrow stress (e.g. sickle cell anemia)Treatment is supportive as infection is self-limited.;

122
Q

Biopsy of an individual with pancytopenia (anemia, thrombocytopenia, and leukopenia) reveals an empty, fatty marrow – what is your diagnosis? What etiologies are associated with this disease?

A

Aplastic Anemia – damage to hematopoietic stem cells

Etiologies include drug, chemicals, viral infections, and autoimmune damage;

123
Q

What is the treatment for Aplastic Anemia?

A
  1. Cessation of any causative drugs;2. Supportive care with transfusions and marrow-stimulating factors (e.g. EPO, 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.;
124
Q

What is a myelophthisic process?

A

Pathologic process (e.g. metastatic cancer) that replaces bone marrow – impairing hematopoiesis and resulting in pancytopenia.;

Pathoma (3 decks)

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