hyperproliferative

Question 1

increased RBC destruction results in (3)

Answer 1

1. shortened RBC survival
2. increase in erythropoiesis as the bone marrow compensates
3. increased in reticulocytes

Question 2

are we going to see an increased reticulocyte increase in hyperproliferative anemia

Answer 2

yep

Question 3

Depends on severity & rate of hemolysis
Pallor (pale skin)
Fatigue
Dyspnea
Icterus (yellow conjunctiva)
Jaundice (yellow skin)
Enlarged spleen (extra-vascular)
Dark urine (intra-vascular)

Answer 3

acute manifestation of hyperproliferative anemia

Question 4

Pigment Gallstones

Skin ulcers

Aplastic crises
- Associated with parvovirus infection
- Severe anemia and reticulocytopenia
Congestive heart failure

Folic acid deficiency

Answer 4

chronic manifestations of hyperproliferative anemia

Question 5

lab findings in hemolytic anemia

1. _________reticulocyte count
2. __________ peripheral blood smear
3. _________ indirect bilirubin in serum
4. ______ haptoglobin - consumption
5. ___________ LDH (lactate dehydrogenase)
6. __________urine urobilinogen
7. Intravascular: (3)

Answer 5

1.Increased reticulocyte count
2.Abnormal peripheral blood smear
3.Increased indirect bilirubin in serum
4.Low haptoglobin - consumption
5.Increased LDH (lactate dehydrogenase)
6.Increased urine urobilinogen
7. Intravascular:
Hemoglobinemia
Hemoglobinuria
Urine hemosiderin

Question 6

Hereditary Spherocytosis (HS)

1. prevalence
2. inheritance
3. Defects in
4. Effects on vertical interactions between the
5. Decreased membrane
6. Loss of membrane through RES
7. MCHC will be
8. diagnostic
9. clinical

Answer 6

1. most common inherited membrane defect (1 in 2,500 N. Europe)
2. Autosomal dominant 75% Recessive 25%
3. Defects in spectrin, ankyrin, band 3, pallidin (band 4.2)
4. Effects on vertical interactions between the membrane skeleton and the lipid bilayer
5. Decreased membrane deformability
6. Loss of membrane through RES
   RBC becomes spherical
7. MCHC will be increased
8. EMA binding (eosin-5-maleimide)
   fluorescent dye binding to RBC
   membrane proteins, lower in HS
9. splenomegaly, gallstones, hyper-hemolytic crises

Question 7

Abnormal osmotic fragility test *

Answer 7

Hereditary Spherocytosis (HS)

Question 8

Hereditary Elliptocytosis (HE)

2. Effects on _____ interactions between cytoskeletal proteins
3. inheritance
4. severity of hemolytic anemia?
5. ______on peripheral blood smear

Answer 8

1. defects in spectrin, protein 4.1, glycophorin C
2. Effects on horizontal interactions between cytoskeletal proteins
3. Autosomal dominant
4. Mild hemolytic anemia (milder than HS)
5. Elliptocytes on peripheral blood smear

Question 9

G6PD deficiency:

1. inheritance
2. variants (a) and (b)
3. common cause of
4. on smear we expect to see
5. positive ______ with supravital stains
6. diagnosis

. 7. avoid

Answer 9

1. x-linked
2. (a) african variant- mild only older rbc are enzyme deficient(b) mediterranean- all rbc deficient
3. common cause of neonatal jaundice
4. ghost cells and bite cells
5. positive Heinz bodies
6. (a) african variant cannot be diagnosed after acute oxidant stress (b) Mediterranean at any time
7. avoid sulfa drugs, fava beans

Question 10

Enzyme defects in the EMG pathway can lead to RBC hemolysis

most common deciency is

Answer 10

pyruvate kinase deficiency

Question 11

Pyruvate kinase deficiency:

1. inheritance
2. Deficiency in ____ production induces cell rigidity
3. Causes
4. Diagnosis made by
5. _________ RBC on smear during hemolytic episodes
6. Treatment:

Answer 11

1. Autosomal recessive disorder
2. Deficiency in ATP production induces cell rigidity
3. Causes red cell hemolysis, splenomegaly, Jaundice
4. Diagnosis made by enzyme assay
5. Abnormal RBC on smear during hemolytic episodes
6. Treatment: red cell transfusions and/or splenectomy

Question 12

Warm AIHA

1. Caused by _____ antibodies RBC agglutination at warm temps
2. Causes: Idiopathic
   Malignancy (Lymphoma, multiple myeloma) Rheumatologic disease
3. associated Drugs
4. treatment

Answer 12

Warm AIHA

1. Caused by IgG antibodies RBC agglutination at warm temps
2. Causes: Idiopathic
   Malignancy (Lymphoma, multiple myeloma) Rheumatologic disease
3. associated Drugs
   - Methyl-Dopa
   - Quinidine
   - PCN
4. treatment- treat underlying cause, suppression of immune system, RBC transfusion of severe, splenectomy

Question 13

Cold AIHA

1. Caused by ____ antibodies Red cell agglutination in cold
2. ___ fixes complement on RBC surface
3. causes:
4. associated with Infections:
5. treatment
6. what is not effective

Answer 13

1. Caused by IgM antibodies Red cell agglutination in cold
2. IgM fixes complement on RBC surface
3. causes: Idiopathic and Malignancy: Lymphomas or solid tumors (infrequent)
4. associated with Infections:
   
   • Mycoplasma
   • EBV (infectious mononucleosis)
   • HIV infection
5. treatment: transfusion of warm blood, plasmapheresis, rituximab to modulate the B cell activity
6. steroids/splenectomy not effective

Question 14

Detects antibodies against RBC in serum (e.g. alloantibodies in hemolytic disease of newborn, transfusion reactions; autoAb in severe AIHA)

Answer 14

Indirect Antiglobulin (Coombs) Test:

Question 15

warm autoimmune hemolysis is

Answer 15

Hemolysis is generally extravascular with spleen removing 
  antibody coated (opsonized) red cells

Question 16

Coombs test detects

Answer 16

C3 on RBC

warm/cold autoimmune hemolysis

Question 17

Cold autoimmune hemolysis is

Answer 17

intravascular and extravascular

Question 18

IgG Antibodies that form against RBC/drug complex i.e. a neoepitope.
Drug or RBC alone won’t react with Ab
Example: Penicillin at high doses.
Removal of drug, stops hemolysis, Ab lost in 2-3 months

Answer 18

Hapten

Question 19

Ab against drug itself but drug-Ab complex binds RBC, activates complement with hemolysis. Occasionally C3+ Coombs test positive. Example: Quinidine
Removal of drug stops hemolysis.
IgG antibody lost in 2-3 months

Answer 19

innocent bystander

Question 20

Drug induces Abs against RBC antigens.
Direct and indirect Coombs are positive.
Hemolysis persists after removal of drug 
until Ig G antibody lost 3-4 months.  
Example: Methyldopa, Fludarabine

Answer 20

autoimmune

Question 21

Damage to the red cells from
constant pounding, while marching
or running. No abnormal cells on
peripheral blood smears.

Answer 21

march hemoglobinuria

Question 22

(4) infections that can cause anemia

Answer 22

1. malaria
2. bartonellosis
3. babesiosis
4. clostridium perfringens

Question 23

Patients with extensive burns may experience ________ hemolysis.

Answer 23

intravascular

Question 24

RBC membrane damage that occurs as RBCs traverse abnormal surfaces or fibrin network deposited on the endothelium

Morphologic hallmark:
schistocytes on blood smear

Answer 24

microangipathic hemolysis

Question 25

causes of microangiopathic hemolysis

Answer 25

1. hemangioma 2. artificial valves 3. DIC- disseminated intravascular coagulopathy 4. TTP- thrombotic thrombocytopenic purpura 5. HUS- hemolytic uremic syndrome

Question 26

Acquired clonal disorder of bone marrow stem cells; due to a mutation in “PIG-A” gene

Answer 26

paroxysmal nocturnal hemoglobinuria

Question 27

paroxysmal nocturnal hemoglobinuria: 1. Deficient synthesis of ____ membrane anchor 2. Absence of ___ linked proteins CD59, CD55 (DAF): Absence of these proteins renders _____ by complement, especially at night (pH is lower) 3. Chronic intravascular hemolysis due to 4. Associated with

Answer 27

1. Deficient synthesis of glycosylphosphatidylinositol (GPI) membrane anchor 2. Absence of GPI linked proteins CD59, CD55 (DAF) Absence of these proteins renders RBC sensitive to lysis by complement, especially at night (pH is lower) 3. Chronic intravascular hemolysis due to complement-mediated destruction of red cells 4. Associated with thromboses, aplastic anemia, muscle dystonia (bowel spasms), pulmonary hypertension