RBC Disorders Flashcards
1
Q
What is the role of ferroportin?
A
Transports iron enterocytes –> blood
2
Q
What is the role of transferrin?
A
Transports iron in blood –> liver & bone marrow macrophages
3
Q
How are measures of serum ferritin & TIBC related?
A
Always opposite! Iron stores versus iron transferrin in blood
4
Q
What is the most common of iron deficiency anemia in:
- Infants
- Children
- Adults
- Elderly
A
- Breast feeding, prematurity
- Poor diet
- Peptic ulcer disease (males) or menorrhagia/pregnancy (females)
- Colon polyps/carcinoma or hookworm
5
Q
Why are individuals with a gastrectomy at risk for iron deficiency anemia?
A
Acid secreted by parietal cells in stomach aids in iron absorption by maintaining Fe2+ state
6
Q
What are the four stages of iron deficiency anemia?
A
- Storage iron depleted
- Serum iron depleted
- Normocytic anemia: fewer cells but normal size
- Microcytic, hypochromic anemia
7
Q
What are some clinical features of iron deficiency anemia?
A
Pica and koilonychia (spoon shaped nails)
8
Q
What are some lab findings of iron deficiency anemia?
A
- Microcytic, hypochromic RBCs w/ increased RDW
- Decreased ferritin, increased TIBC, decreased saturation, decreased serum iron
- Increased free erythrocyte protoporphyrin
9
Q
What is Plummer-Vinson syndrome?
A
Iron deficiency anemia with:
- Esophageal web –> dysphagia
- Atrophic glossitis –> beefy-red tongue
10
Q
What is the most common type of anemia in hospitalized patients?
A
Anemia of chronic disease
11
Q
How does hepcidin play a role in anemia of chronic disease?
A
Hepcidin sequesters iron storage by:
1) Limiting iron transfer from macrophages to erythroid precursors
2) Suppressing EPO production
* Body thinks its an infection and wants to prevent bacteria from getting iron!
12
Q
What are the ringed sideroblasts in sideroblastic anemia?
A
Iron enters mitochondria to form heme; defect in protoporphyrin synthesis so no protoporphyrin; iron stays in mitochondria –> iron-laden mitochondria form a ring around nucleus = ringed sideroblasts
13
Q
What are some causes of sideroblastic anemia?
A
- Congenital: commonly involves ALAS
- Alcoholism: mitochondrial poison
- Lead poisoning: denatures ferrochelatase and ALAD
- B6 Deficiency: B6 cofactor for rate limiting step; commonly side effect of isoniazid treatment for TB
14
Q
Why is there a high serum iron concentration in sideroblastic anemia?
A
Iron overloaded state: excess iron in cells generates radicals –> cause cells to die –> BM macrophages eat up this iron & some released into blood
15
Q
The alpha genes involved in alpha thalassemia are on what chromosome?
A
Four alpha genes on chromosome 16
16
Q
How does alpha thalassemia minor present?
A
Two gene delations lead to mild anemia with increased RBC count
Cis deletion –> East Asians; worse, increased risk in offspring
Trans deletion –> Africans
17
Q
Three alpha gene deletions lead to?
A
Formation of HbH = beta4 –> severe anemia
18
Q
Four alpha gene deletions lead to?
A
Hydrops fetalis: lethal in utero
Formation of Hb Barts = gamma4 - damage RBCs
19
Q
What is the inheritance pattern of thalassemias?
A
Autosomal recessive
20
Q
Which populations are Beta thalassemias commonly seen in?
A
Individuals with African or Mediterranean descent
21
Q
What chromosome are the beta genes for hemoglobin production on?
A
Two beta genes on Chromosome 11
22
Q
What is beta thalassemia minor characterized by?
A
Asymptomatic with increased RBC
Microcytic, hypochromic RBCs and target cells on blood smear
Hb electrophoresis: increased HbA2
23
Q
What is beta thalassemia major characterized by?
A
- Alpha tetramers aggregate and damage RBCs –> ineffective erythropoeisis; making defective RBCs that are eaten by spleen = extravascular hemolysis
- Massive erythyroid hyperplasia –> crewcut skull, facial bones, hepatosplenomegaly (hematopoiesis), risk of aplastic crisis with B19
- Chronic transfusions; may lead to secondary hemochromatosis
- Blood smear with microcytic, hypochromic RBCs with target cells and nucleated RBCs
- Hb electrophoresis with no HbA, increased HbA2 and HbF
24
Q
When does beta thalassemia major usually present?
A
A few months after birth; before that, patients have HbF to compensate
25
Why do we see target cells in thalassemias? What else are they seen in?
Target cells involve loss of central pallor of RBCs and center is instead pink. Decreased Hb in cytoplasm forms membrane blebs where Hb goes to.
*Also seen in other hemoglobinopathies (sickle cell), iron deficiency anemia and liver disease
26
What are some features of macrocytic anemias?
1. Megaloblastic anemia (big RBCs and other cells)
2. Hypersegmented neutrophils (impaired division of granulocytes)
3. Megaloblastic changes in rapidly-dividing epithelial cells (ex: intestinal)
27
What are some causes of macrocytic anemia besides folate and B12 deficiency?
Alcoholism, liver disease, drugs (5-FU, phenytoin)
| *Do not see megaloblastic changes - nuclei are mature
28
What is the most common cause of folate deficiency?
Alcoholics! Poor diet
29
What are some clinical and lab findings of folate deficiency?
1. Macrocytic RBCs & hypersegmented neutrophils
2. Glossitis
3. Decreased serum folate
4. Increased serum homocysteine
5. Normal metylmalonic acid
30
What is the most common cause of B12 deficiency?
Pernicious anemia: autoimmune destruction of parietal cells; seen in middle-older age & associated with other autoimmune diseases
31
What are some other causes of B12 deficiency?
1. Pancreatitis
2. Damage to terminal ileum
3. Dietary deficiency (rare)
32
What are some clinical and lab findings of B12 deficiency?
1. Macrocytic RBCs & hypersegmented neutrophils
2. Glossitis
3. Degeneration of spinal cord - irreversible
4. Decreased serum B12
5. Increased serum homocysteine
6. Increased metylmalonic acid
33
How do you is reticulocyte count corrected for in anemia? How is this number analyzed?
RC X Hematocrit/45
1. Corrected count > 3% --> good bone marrow compensation; peripheral RBC destruction causing anemia
2. Corrected count < 3% --> poor bone marrow compensation; bone marrow underproduction causing anemia
34
What are some features of extravascular hemolysis?
1. Anemia with splenomegaly (eating RBCs)
2. Jaundice (unconjugated bilirubin)
3. Increased risk for bilirubin gallstones
4. Marrow hyperplasia (trying to make more RBCs)
35
How would you describe extravascular hemolysis?
RBC destruction by reticuloendothelial system (spleen, liver, lymph nodes)
36
How would you describe intravascular hemolysis?
Destruction of RBCs within vessels
37
What are some clinical and lab findings of intravascular hemolysis?
1. Hemoglobinemia
2. Hemoglobinuria
3. Hemosiderinuria: from hemosiderin accumulations in tubular cells
4. Decreased free serum haptoglobin
38
What is the inheritance pattern of hereditary spherocytosis?
Autosomal dominant
39
What is the defect in hereditary spherocytosis?
Defect of RBC cytoskeleton-membrane tethering proteins (spectrin, ankyrin, band 3.1)
40
Why are spherocytes seen in hereditary spherocytosis?
No cytoskeleton to maintain shape --> loss of membrane --> round cells with loss of central pallor
41
What is the extravascular hemolysis in hereditary spherocytosis?
Spherocytes unable to maneuver through splenic sinusoids --> eaten by spleen
42
What are the clinical and laboratory findings of hereditary spherocytosis?
1. Spherocytes with loss of central pallor
2. Increased RDW and MCHC
3. Extravascular signs
4. Increased risk for aplastic crisis w/ Parvovirus B19
43
How do you diagnose hereditary spherocytosis?
Osmotic fragility test; spherocyte bursts in hypotonic solution (water enters cell) because has no membrane
44
How do you treat hereditary spherocytosis?
Splenectomy: anemia bye bye but spherocytes stay & may see Howell-Jolly bodies
45
Sickle cell anemia involves which mutation?
Autosomal recessive mutation in Beta chain; glutamic acid --> valine
46
How many abnormal genes are needed for someone to have sickle cell disease?
Two mutated beta genes --> >90% HbS
47
What conditions cause HbS to sickle?
Deoxygenated states: acidosis, high altitude, dehydration, hypoxemia
48
How does sickle cell involve extravascular hemolysis?
Cells sickle and de-sickle --> RBC membrane damage
| Reticuloendothelial system eats up RBCs with damaged membranes
49
How does sickle cell involve intravascular hemolysis?
RBCs with damaged membranes dehydrate --> hemolysis --> decreased haptoglobin and target cells
50
What does irreversible sickling lead to, which in turn causes the major complications of sickle cell disease?
Vaso-occlusion
51
What are 5 complications of vaso-occlusion in sickle cell?
1. Dactylitis (common in infants)
2. Autosplenectomy (increased risk of infection w/ encapsulated organisms; salmonella typhi osteomyelitis, HJ bodies)
3. Acute chest syndrome (often following pneumonia - increases chances of deoxygenation)
4. Pain crisis
5. Renal papillary necrosis (hematuria, proteinuria)
52
What is sickle cell trait characterized by? What place in the body might be susceptible to damage?
One normal, one mutated chain. < 50% HbS in RBCs so does not sickle except in RENAL MEDULLA
*Extreme hypoxia and hypertonicity of medulla can cause sickling
53
What is the metabisulfite screening test used for?
Causes with any amount of HbS (sickle cell disease and trait) to sickle
54
What is the inheritance pattern for Hemoglobin C? What is the mutation?
Autosomal recessive; glutamic acid --> lysine
55
How do individuals with Hemoglobin C present?
Mild anemia due to extravascular hemolysis; hemoglobin C crystals in RBCs on smear
56
How does someone get paroxysmal nocturnal hemoglobinuria (PNH)?
ACQUIRED defect in myeloid stem cells resulting in absent GPI
57
What are the roles of decay accelerating factor (DAF) and Membrane Inhibitor of Reactive Lysis (MIRL)?
On surface of RBCs and protect against complement-mediated damage by inhibiting C3 convertase
58
Why is paroxysmal nocturnal hemoglobinuria episodic and at night?
Shallow breathing during night leads to a mild respiratory acidosis which activates complement
59
Which types of cells are lysed in PNH?
RBCs, WBCs, platelets
60
Which test is used to screen for PNH?
Sucrose test.
61
Which test is used to diagnose PNH?
Acidified serum test or flow cytometry (detects lack of CD55/CD59)
62
What is the main cause of death in individuals with PNH?
Thrombosis of hepatic, portal or cerebral veins; destroyed platelets release cytoplasmic contents into circulation --> thrombosis
63
Name 2 complications of PNH.
1. Iron deficiency anemia (losing Hb)
| 2. AML (10% of patients; more susceptible to a 2nd mutation)
64
What is the inheritance pattern for G6PD deficiency?
X linked recessive
65
What are the two major variants of G6PD deficiency? Which is more severe?
1. African Variant: mildly reduced half life of G6PD --> no G6PD in older RBCs --> only older RBCs lysed
2. Mediterranean Variant: markedly reduced half life of G6PD --> older & younger RBCs lysed
66
What are Heinz bodies?
Precipitated Hb
67
Under what conditions will you see symptoms of G6PD deficiency?
Oxidative stress: infections, drugs (primaquine, sulfa, dapsone), fava beans
68
How do extravascular and intravascular hemolysis occur in G6PD deficiency? Which is predominant?
Splenic macrophages bite Heinz bodies --> bite cells --> some extravascular hemolysis can occur where macrophages eat entire cell but mostly intravascular hemolysis
69
What do patients with G6PD deficiency present with?
Hemoglobinuria and back pain (Hb is nephrotoxic) hours after oxidative stress
70
What is used to screen for G6PD deficiency?
Heinz preparation
71
What is used to diagnose G6PD deficiency? When is this test performed?
Enzyme studies; performed weeks after hemolytic episode resolves
72
What are the two types of immune hemolytic anemia?
IgG mediated (extravascular hemolysis) and IgM mediated (intravascular hemolysis)
73
Which disease does the blood smear of IgG-mediated immune hemolytic disease resemble?
Hereditary spherocytosis! You also see spherocytes with warm agglutinins
74
How do spherocytes form in IgG-mediated immune hemolytic disease?
IgG binds RBCs in warm temperature of central body --> splenic macrophages consume antibody-coated RBC --> spherocytes --> spherocytes eventually eaten by splenic macrophages
75
What is IgG-mediated immune hemolytic anemia associated with?
SLE (MCC), CLL, drugs (penicillin & cephalosporins)
76
How can drugs induce IgG-mediated immune hemolytic anemia?
1. Drug may attach to RBC membrane and antibody binds to complex (penicillin)
2. Drug may induce production of autoantibodies that bind to self antigens on RBCs (methyldopa)
77
How do you treat IgG-mediated immune hemolytic anemia?
Treat underlying cause, IVIG, splenectomy (two birds one stone)
78
What process causes hemolysis in IgM-mediated immune hemolytic anemia?
IgM binds RBCs and fixes complement in cold temperature of extremities
79
What is IgM Mediated immune hemolytic anemia associated with?
Mycoplasma pneumoniae and infectious mononucleosis
80
Which test is used to diagnose immune hemolytic anemia? Which is more important?
Coombs test - direct and indirect
| Direct most important test for IHA
81
What is malaria transmitted by?
Anopholes mosquito
82
What organs/cells does Plasmodium infect?
RBCs and liver
83
What type of hemolysis occurs in malaria? What is the cause of the hemolysis?
Intravascular hemolysis and cyclical fever occur as a part of the Plasmodium life cycle
84
Is there any extravascular hemolysis in malaria?
Yes! Spleen consumes some infected RBCs --> mild extravascular hemolysis with splenomegaly
85
What are some causes of anemia due to underproduction?
Renal failure (decreased EPO), damage to bone marrow precursor cells
86
How does Parvovirus B19 cause red cell aplasia?
Infects RBC precursors and halts erythropoiesis --> significant anemia in people dependent on RBCs!
87
How do you treat Parvovirus B19?
Supportive treatment; self-limited infection
88
What is aplastic anemia? What is it caused by?
Damage to HSCs resulting in pancytopenia & low reticulocyte count; causes: drugs/chemicals, viral infections, autoimmune damage
89
What does the biopsy of someone with aplastic anemia show?
Empty, fatty marrow
90
How do you treat aplastic anemia?
Treat underlying cause; can use immunosuppression and may need bone marrow transplant
91
What is a myelopthisic process?
Pathologic process (metastatic cancer) that replaces bone marrow --> impairs hematopoiesis --> pancytopenia
