Fa: Hem / Onc - Pathology (Rbc & Platelets) - 3

Front 1

What is the cause of Paroxysmal Nocturnal Hemoglobinuria?

Back 1

↑ Complement mediated RBC Lysis:
- Impaired synthesis of GPI anchor for decay-accelerating factor that protects RBC membrane from complement
- Acquired mutation in a hematopoietic stem cell

Front 2

What is there risk of in patients with Paroxysmal Nocturnal Hemoglobinuria?

Back 2

Increased incidence of acute leukemias

Front 3

What lab findings are there in Paroxysmal Nocturnal Hemoglobinuria?

Back 3

- Coombs (-) Hemolytic anemia
- Pancytopenia
- Venous Thrombosis
- CD55 / 59 (-) RBCs on flow cytometry

Front 4

How do you treat Paroxysmal Nocturnal Hemoglobinuria?

Back 4

Eculizumab

Front 5

What are the types of extrinsic hemolytic normocytic anemias?

Back 5

- Auto-immune hemolytic anemia
- Microangiopathic anemia
- Macroangiopathic anemia
- Infections

Front 6

What are the types of autoimmune hemolytic anemia?

Back 6

- Warm agglutinin (IgG)
- Cold agglutinin (IgM)

Front 7

What is warm agglutinin auto-immune hemolytic anemia associated with?

Back 7

- IgG
- Chronic anemia seen in in SLE, CLL, or with certain drugs (eg, α-methyldopa)
- Can be idiopathic

Front 8

What is cold agglutinin auto-immune hemolytic anemia associated with?

Back 8

- IgM
- Acute anemia triggered by cold, seen in CLL, Mycoplasma pneumonia infections, or infectious mononucleosis
- Can be idiiopathic

Front 9

What are the lab results for patients with auto-immune hemolytic anemia?

Back 9

Coombs test (+)

Front 10

What are the types of Coombs tests? What do they indicate?

Back 10

- Direct Coombs test: anti-Ig antibody (Coombs reagent) added to patient's blood, RBCs agglutinate if RBCs are coated in Ig
- Indirect Coombs test: normal RBCs added to patient's serum, if serum has anti-RBC surface Ig, RBCs agglutinate when anti-Ig antibodies (Coombs reagent) is added

Front 11

What test adds anti-Ig antibody (Coombs reagent) to patient's blood? What is a positive result?

Back 11

Direct Coombs test:
- Positive: RBCs agglutinate, indicates RBCs are coated with Ig

Front 12

What test adds normal RBCs to the patient's serum and then adds anti-Ig antibodies (Coombs reagent)? What is a positive result?

Back 12

Indirect Coombs test:
- Positive: RBCs agglutinate when reagent is added if serum has anti-RBC surface Ig

Front 13

What causes Microangipathic Anemia?

Back 13

RBCs are damaged when passing through obstructed or narrowed vessel lumina
- Seen in DIC, TTP-HUS, SLE, and malignant hypertension

Front 14

What causes Macroangipathic Anemia?

Back 14

RBCs are damaged mechanically because of prosthetic heart valves or aortic stenosis

Front 15

What are the findings of patients with Microangipathic vs Macroangiopathic Anemia?

Back 15

Both have schistocytes (helmet cells) on blood smear due to destruction of RBCs

Difference is based on cause

Front 16

What infections can cause an extrinsic hemolytic normocytic anemia?

Back 16

- Malaria
- Babesia

Front 17

What type of anemia has the following lab values:
- Serum iron: ↓
- Transferrin or TIBC: ↑
- Ferritin: ↓
- % Transferrin Saturation (serum iron/TIBC): ↓↓

What is the primary change?

Back 17

Iron Deficiency Anemia

Primary change is ↓ in serum iron

Front 18

What type of anemia has the following lab values:
- Serum iron: ↓
- Transferrin or TIBC: ↓
- Ferritin: ↑
- % Transferrin Saturation (serum iron/TIBC): -

What is the primary change?

Back 18

Anemia of Chronic Disease

Primary change is ↑ in ferritin

Front 19

What type of anemia has the following lab values:
- Serum iron: ↑
- Transferrin or TIBC: ↓
- Ferritin:↑
- % Transferrin Saturation (serum iron/TIBC): ↑↑

What is the primary change?

Back 19

Hemochromatosis

Primary change is ↑ in serum iron

Front 20

What type of anemia has the following lab values:
- Serum iron: -
- Transferrin or TIBC: ↑
- Ferritin: -
- % Transferrin Saturation (serum iron/TIBC): ↓

What is the primary change?

Back 20

Pregnancy or OCP use

Primary change is ↑ in Transferrin or TIBC (indirectly measures transferrin)

Front 21

What is the function of Transferrin?

Back 21

Transports iron in the blood

Front 22

What is the function of Ferritin?

Back 22

Primary iron storage protein in body

Front 23

Why does transferrin decrease in anemia of chronic disease?

Back 23

Evolutionary reasoning: pathogens use circulating iron to thrive, the body has adapted a system in which iron is stored within the cells of the body and prevents pathogens from acquiring circulating iron

Front 24

Which types of anemia have decreased transferrin (protein that transports iron in blood)?

Back 24

- Anemia of chronic disease
- Hemochromatosis

Front 25

Which types of anemia have increased transferrin (protein that transports iron in blood)?

Back 25

- Iron deficiency anemia
- Pregnancy / OCP use (primary change)

Front 26

Which types of anemia have decreased ferritin (1° iron storage protein in body)?

Back 26

Iron deficiency anemia

Front 27

Which types of anemia have increased ferritin (1° iron storage protein in body)?

Back 27

- Anemia of chronic disease (1° change)
- Hemochromatosis

Front 28

Which types of anemia have decreased % transferrin saturation?

Back 28

- ↓↓ in iron deficiency anemia
- ↓ in pregnancy / OCP use

Front 29

Which types of anemia have increased % transferrin saturation?

Back 29

Hemochromatosis

Front 30

What are the types of leukopenias?

Back 30

- Neutropenia
- Lymphopenia
- Eosinopenia

Front 31

What is the definition and possible causes of Neutropenia?

Back 31

- Absolute neutrophil count <1500 cells / mm3

Causes:
- Sepsis / post-infection
- Drugs (including chemotherapy)
- Aplastic anemia
- SLE
- Radiation

Front 32

What is the definition and possible causes of Lymphopenia?

Back 32

- Absolute lymphocyte count <1500 cells / mm3 (<3000 cells/mm3 in children)

Causes:
- HIV
- DiGeorge syndrome
- SCID
- SLE
- Corticosteroids
- Radiation
- Sepsis
- Post-operative

Front 33

How do corticosteroids affect levels of leukocytes?

Back 33

- Corticosteroids cause neutrophilia, but eosinopenia and lymphopenia
- Corticosteroids ↓ activation of neutrophil adhesion molecules, impairing migration out of the vasculature to sites of inflammation
- In contrast, corticosteroids sequester eosinophils in lymph nodes and cause apoptosis of lymphocytes

Front 34

What are the possible causes of Eosinopenia?

Back 34

- Cushing syndrome
- Corticosteroids

Front 35

What is the name of the hereditary or acquired conditions of defective heme synthesis? What do they lead to?

Back 35

Porphyrias:
- Leads to accumulation of heme precursors

Front 36

How does lead affect heme synthesis?

Back 36

Lead inhibits specific enzymes needed in heme synthesis, leading to a condition similar to porphyrias

Front 37

What are the types of porphyrias?

Back 37

- Acute intermittent porphyria
- Porphyria cutanea tarda

Front 38

What enzymes in heme synthesis are affected by lead poisoning?

Back 38

- Ferrochelatase
- ALA dehydratase

Front 39

What substrates accumulate as a result of lead poisoning?

Back 39

- Protoporphyrin
- δ-ALA (blood)

Front 40

What are the presenting symptoms of lead poisoning?

Back 40

- Microcytic anemia
- GI and kidney disease
- Children: exposure to lead paint → mental deterioration
- Adults: environmental exposure (battery, ammunition, radiator factor) → headache, memory loss, demyelination

Front 41

What enzyme is affected by Acute Intermittent Porphyria?

Back 41

Porphobilinogen Deaminase

Front 42

What substrates accumulate as a result of Acute Intermittent Porphyria?

Back 42

- Porphobilinogen
- δ-ALA
- Corporphobilinogen (urine)

Front 43

What are the presenting symptoms of Acute Intermittent Porphyria?

Back 43

Symptoms 5 P's:
- Painful abdomen
- Port wine-colored urine
- Polyneuropathy
- Psychological disturbances
- Precipitated by drugs, alcohol and starvation

Front 44

What can cause presentation of symptoms of Acute Intermittent Porphyria?

Back 44

- Drugs
- Alcohol
- Starvation

Front 45

What enzyme is affected by Porphyria Cutanea Tarda?

Back 45

Uroporphyrinogen Decarboxylase

Front 46

What substrates accumulate as a result of Porphyria Cutanea Tarda?

Back 46

Uroporphyrin (tea-colored urine)

Front 47

What are the presenting symptoms of Porphyria Cutanea Tarda?

Back 47

- Blistering cutaneous photosensitivity
- Tea-colored urine (due to uroporphyrin)

Front 48

What disease is caused by a defective Ferrochelatase and ALA dehydratase? What accumulates and what are the presenting symptoms?

Back 48

Lead Poisoning
- Accumulation of protoporphyrin and δ-ALA (blood)
- Microcytic anemia
- GI and kidney disease
- Children: exposure to lead paint → mental deterioration
- Adults: environmental exposure (battery, ammunition, radiator factor) → headache, memory loss, demyelination

Front 49

What disease is caused by a defective Porphobilinogen Deaminase? What accumulates and what are the presenting symptoms?

Back 49

Acute Intermittent Porphyria
- Accumulation of Porphobilinogen, δ-ALA, and Coporphobilinogen (urine)

Symptoms 5 P's:
- Painful abdomen
- Port wine-colored urine
- Polyneuropathy
- Psychological disturbances
- Precipitated by drugs, alcohol and starvation

Front 50

How do you treat Acute Intermittent Porphyria?

Back 50

Glucose and Heme, which inhibit ALA synthase

Front 51

What disease is caused by a defective Uroporphyrinogen Decarboxylase? What accumulates and what are the presenting symptoms?

Back 51

Porphyria Cutanea Tarda
- Accumulation of uroporphyrin (tea-colored urine)
- Blistering cutaneous photosensitivity

Front 52

What is the most common porphyria?

Back 52

Porphyria Cutanea Tarda
- Defect in uroporphyrinogen decarboxylase
- Accumulation of uroporphyrin (tea-colored urine)
- Blistering cutaneous photosensitivity

Front 53

What enzyme is defective in sideroblastic anemia?

Back 53

δ-Aminolevulinic Acid Synthase (rate-limiting step of heme synthesis
- X-linked

Front 54

How does the level of heme affect ALA synthase activity?

Back 54

↓ Heme → ↑ ALA Synthase activity
↑ Heme → ↓ ALA Synthase activity

(ALA Synthase is the rate-limiting step in heme synthesis)

Front 55

What tests can be used to assess for coagulation disorders? What do they test?

Back 55

- PT test - function of common and EXTRINSIC pathway (factors I, II, V, VII, and X)
- PTT test - function of common and INTRINSIC pathway (all factors except VII, and XIII)

Front 56

Defects in what factors can cause an increased PT time?

Back 56

Factors I, II, V, VII, and X

Front 57

Defects in what factors can cause an increased PTT time?

Back 57

All factors except VII and XIII

Front 58

Which disorders cause a normal PT but a prolonged PTT?

Back 58

Hemophilia A and B
- Hemophilia A: deficiency of Factor VIII
- Hemophilia B: deficiency of Factor IX

Affects intrinsic pathway

Front 59

What are the signs / symptoms associated with hemophilia A or B?

Back 59

- Prolonged PTT but normal PT
- Macrohemorrhage in hemophilia: hemarthroses (bleeding into joints), easy bruising

Front 60

How do you treat Hemophilia A or B?

Back 60

Hemophilia A: treat with recombinant factor VIII