Haemolytic anaemia Flashcards
(120 cards)
1
Q
Designate the specific types of hemolytic anemias as due to either intrinsic or extrinsic red blood cell defects
A
- At each stage, check whether they are intravascular or extravascular
- Intrinsic: pathology within the red blood cell itself: INTRINSIC
- Extrinsic: pathology outside of the cell
2
Q
List the different causes of intrinsic red blood cell defects
A
- Membrane defects
Hereditary Spherocytosis
Hereditary elliptocytosis
Paroxysmal Nocturnal Hemoglobinuria - Abnormal Haemoglobin (we don’t have Thalassemia here = MICROCYTIC ANAEMIA)
Sickle cell Disease
HbC disease - Deficient Enzymes
G6DP deficiency
Pyruvate Kinase deficiency
MAD
3
Q
List the different causes of extrinsic red blood cell defects
A
- Blood loss > 1 week (reticulocytosis)
- Immune-mediated hemolysis
- Micro/ macroangiopathic hemolytic anemia
- Malaria
4
Q
Distinguish between intrinsic and extrinsic RBC defects
A
Intrinsic - defect withing the RBS itself
structural proteins, enzymes, membrane defects
Extrinsic - defects outside of the RBC
mechanical destruction, autoimmune
5
Q
Distinguish between intravascular and extravascular hemolysis
A
Intravascular - a disease in which hemolysis occurs within the blood vessel (abnormal)
- Hemoglobinuria
Extravascular - disease in which hemolysis occurs outside of the blood vessel (spleen)
- Jaundice
6
Q
Explain the finding of hemoglobinuria due to intravascular hemolysis
A
- RBC is being destroyed within the blood vessel (not where it normally gets destroyed)
- Releasing Hb in the vasculature
- Hb most likely won’t get further degraded (because it’s not at the level of the spleen)
- Hb will get filtered through the kidney
= hemoglobinuria
red urine after waking up or after exercise
7
Q
Describe the process of red blood cell destruction by extravascular hemolysis
A
- reticuloendothelial system
- spleen
- RBCs removed from the vasculature, taken to cords of Billroth, splenic macrophage will destroy it
- heme -> Biliverdin -> Bilirubin (unconjugated/ indirect = lipid soluble = JAUNDICE/ ICTERUS)
- SPLEEN gets destroyed - susceptible to encapsulated microorgansims
8
Q
What is the most common cause of Iron Deficiency Anaemia?
A
Loss of Blood through menstruation (in women)
9
Q
What type of anaemia is Haemolytic anaemia?
A
Normocytic anemia
Increased reticulocytosis - bone marrow trying to compensate for the loss (corrected reticulocyte count > or equal to 3%)
10
Q
What type of anaemia is Haemolytic anaemia?
A
Normocytic anemia
Increased reticulocytosis - bone marrow trying to compensate for the loss (corrected reticulocyte count > or equal to 3%)
11
Q
List 3 pathologies that lead to extravascular hemolysis
A
- Sickle cell
- Spherocytosis
- IgG + C3b (autoimmune) - opsonins
12
Q
Describe the laboratory findings related to extravascular hemolysis
A
- Jaundice
- Unconjugated Bilirubin increased
- Lactate dehydrogenase increased
13
Q
Explain why haptoglobin levels are decreased in intravascular hemolysis
A
- Haptoglobin = binds with high affinity to free Hb
- High levels of Hb use up Haptoglobin
- Measure free Haptoglobin
- Complex removed by macrophages
- UCB is not high enough to produce jaundice
14
Q
List laboratory findings related to intravascular hemolysis
A
- decreased Haptoglobin
- Increased Lactate Dehydrogenase (non- specific)
15
Q
Explain why jaundice is either mild or not found in intravascular hemolysis
A
- Hb not broken down
- Not enough unconjugated bilirubin to cause Jaundice
16
Q
Clinical Findings of Hemolytic anemias - intravascular features
A
- Hemoglobinemia + hemoglobinuria
- decreased serum haptoglobin
- increased serum LDH
17
Q
Clinical Findings of Hemolytic anemias - extravascular features
A
- Jaundice
- increased serum LDH
18
Q
Clinical Findings of Hemolytic anemias - both
A
- increased serum LDH
19
Q
Explain why hereditary spherocytosis results in extravascular hemolysis
A
- spherocytes are broken down by the spleen as they are abnormal RBCs
- Spherocytes - membrane fragments are lost and the rbcs lose their biconcave shape - misshapen RBCs are cleared by the spleen - ANEMIA
- Jaundice
20
Q
State the 2 proteins most commonly mutated in hereditary spherocytosis
A
- Ankyrin
- Spectrin
In cell membrane
21
Q
Identify spherocytes on a peripheral blood smear
A
- Spherical
- No central parlor
- Can differentiate between spherocytes and warm autoimmune hemolysis by Coombs test (anti-human globulin test) - negative in hereditary spherocytosis
2 diff:
- HS
- Warm type of autoimmune hemolytic anemia
22
Q
Explain the osmotic fragility test used to diagnose hereditary spherocytosis
A
- Spherocytes are more fragile
- They have a decreased ability to expand
- osmotic pressure increases in spherocytes
- when placed in saline - they cells expand
23
Q
Why do pigment stones form in Hereditary Spherocytosis?
A
- Due to increased destruction of RBCs
- Increase in bilirubin - pigment stones
- Splenomegaly
24
Q
Describe the consequences of a parvovirus B19 infection in a patient with hereditary spherocytosis
A
- Bone marrow shut down
- Aplastic crisis with Parvovirus infection - decreased RBC lifespan
25
State the test used to diagnose hereditary spherocytosis
- Negative Coombs test to differentiate between autoimmune disease and HS
- Diagnosis: Osmotic fragility test
- Spherocytes contain more Hb - when in a hypotonic solution, they expand and burst - increased hemolysis
- Decreased ability to expand
26
State the result of a Coombs test in a patient with hereditary spherocytosis
- Negative
- No antibodies on RBCs
27
Recognize that glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate shunt
- rate-limiting step in the pentose pathway shunt
- forms NADPH- needed for glutathione (protects RBC from antioxidants)
- Mutations decrease the half-life of the enzymes
- normal - 62 days
mutation - 13 days (not a lot of time for an enzyme)
28
State the inheritance pattern for G6PD deficiency
- X-linked recessive
- Males at greater risk
- Females can have the trait
29
What type of anemia does G6PD deficiency causes?
Normocytic hemolytic anemia
30
Describe the relationship between the pentose phosphate pathway, NADPH, and glutathione
- G6PD needed in the Pentose pathway
- forms NADPH
- needed for the recycling of glutathione (which fights against free radicals)
- Protects the RBC from free radical damage+ and repairs damage caused by oxidative stress
31
Explain the findings of Heinz bodies and bite cells in G6PD deficiency
- G6PD deficiency leads to oxidative damage
- Hb precipitation - causes denatured RBCs = Heinz bodies
- Cells with membrane damage + are partially consumed by macrophages
- The damaged cells are cleared in the spleen (bite cells)
32
What type of beans cause oxidative stress?
Fava beans
33
What type of beans cause oxidative stress?
Fava beans
- eaten in the Mediterranean countries, Italy, Lebanon
- free radical
34
What drugs cause oxidative stress?
Antimalarial drugs
Atovaquone/Proguanil (Malarone) Chloroquine. Doxycycline. Mefloquine. Primaquine
35
Is G6PD deficiency intravascular or extravascular?
- based upon the exposure to the oxidative stress
- both exist with G6PD DEF
- If it is completely bitten by the phagocytic cells - INTRAVASCULAR HEMOLYSIS
- If it is just a bite cell - RBC is taken out of the vasculature and degraded by the spleen - EXTRAVASCULAR
- Patient can have jaundice or hemoglobinuria/ hemoglobinemia
36
What other condition can be present alongside G6PD def?
- Catalase-positive susceptibility (staphylococcus)
- Neutrophils are affected (they need NADPH to make NADPH oxidase - which is used in phagocytosis)
- Not just seen in chronic granulomatous disease - only one cell affected (neutrophils)
- In G6PD DEF - two cells are affected - RBC and neutrophils
37
What does NADPH stand for?
nicotinamide adenine dinucleotide phosphate (NADPH)
38
What is the principal function of glutathione in erythrocytes?
Prevent oxidative damage
39
Which of the following are inclusions within red blood cells composed of denatured hemoglobin?
Heinz bodies
40
Which cells are characteristic of an acute attack in a patient with G6PD deficiency?
bite cell
41
What happens to the RBC when a patient with G6PD def has oxidative stress?
- Hb within RBC gets damaged and precipitates
- Hb within RBC that becomes unrecognizable - becomes an antigen
- Phagocytic cells are attracted to it - bite taken out of it
42
What is a bite cell?
Cells with membrane damage + are partially consumed by macrophages
43
The reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) is required in which conversion?
Oxidized glutathione to reduced glutathione
44
Which of the following primarily protects the erythrocyte against free radical damage?
Reduced Glutathione (GSH)
45
Recognize the ethnicities most commonly affected by G6PD deficiency
- African
- Mediterranean
- X-linked
46
List the clinical findings associated with the episodic hemolysis of G6PD deficiency
- palor, fatigue, jaundice
47
List the common triggers for an episode of hemolysis in a patient with G6PD deficiency
- caused by: fava beans, oxidizing drugs(sulfonamides, nitrofurans, antimalarials), infection
48
State the deficiency that leads to paroxysmal nocturnal hemoglobinuria (PNH)
- GPI- linked proteins on RBCs, neutrophils, and platelets
49
Explain why patients with PNH may present with a thrombus
- excess stimulation of platelet function - thrombi formation
- all over body
- portal hypertension - if portal vein thrombosis
50
Explain why patients with PNH present with hemoglobinuria
- intravascular hemolysis
- episodic, nocturnal
- haptoglobin decreases as it binds to Hb
- The complex is excreted by the kidneys in urine
- Fe is lost alongside Hb
- results in iron deficiency anemia
51
Which types of cells are affected in paroxysmal nocturnal hemoglobinuria?
RBCs, neutrophils, and platelets
52
What are the manifestations of portal vein thrombosis?
Hemorrhoids, Caput medusae, Esophageal varices, and ascites
53
Which structures with thrombosis result in Budd-Chiari syndrome?
Hepatic vein
54
Which type of anemia can be accompanied by paroxysmal nocturnal hemoglobinuria?
iron deficiency anemia
55
What is deficient as a result of paroxysmal nocturnal hemoglobinuria?
GPI-linked proteins
56
Describe the normal function of decay-accelerating factor
- a type of GPI -linked protein
- a factor that controls complement activity
57
Explain the consequence of an absence of decay-accelerating factor
- cannot regulate complement activity
- affects RBCs and platelet
- excess platelet activity
- hemolysis - intravascular
58
Explain why the hemolysis in PNH occurs at night
- acidic environment
- lower CO2
- optimal environment for the complements
- destroys RBCs
59
In the absence of the decay accelerating factor (DAF), RBCs are susceptible to which of the following?
Complement-mediated damage
60
Hereditary angioedema results from a deficiency of which of the following?
C1 esterase inhibitor
- vasodilation around the mucous membrane
61
Hemolysis in PNH is mainly nocturnal due to which of the following?
Acidic environment
- at night -> breathing rate slows down
- increased CO2 in body
- slightly acidic
62
Hypercoagulable state in PNH is due to which of the following?
Increased platelet function
63
List the scenarios that can lead to hemolysis in a patient with paroxysmal hemoglobinuria (PNH)
- Respiratory acidosis at night
- Lactic acidosis during exercise (cramps) - metabolic acidosis
64
Recognize that PNH can lead to iron deficiency anemia
- losing Hb
- Losing Iron
- it is attached to the Heme
65
State the test used to diagnose PNH
- flow cytometry - complement action in the patient's blood is tested
- look for GPI-linked proteins
66
State the CD markers that are reduced or absent in paroxysmal nocturnal hemoglobinuria (PNH)
CD55 (DAF)
CD59 (MIRL)
67
List the laboratory studies that can be done to diagnose PNH
- flow cytometry
- Fluorescent Aerolysin (FLAER)
68
State what the leukocyte alkaline phosphatase test is measuring
- low LAP score in PNH
- LAP is also decreased in CML
- LAP measures the functionality of neutrophils
69
Which of the following CD markers marks for membrane inhibitor of reactive lysis (MIRL)?
CD59
70
For what types of cells does leukocyte alkaline phosphatase measure their functionality?
Neutrophils
71
Which condition presents with increased leukocyte alkaline phosphatase?
Leukemoid reaction
72
State the point mutation responsible for sickle cell anemia
- substitution mutation
- Glutamic acid is replaced by valine at position 6 of the beta chain
- screen - E6V
- Glutamic acid E6V
- heterozygous vs homozygous pattern
73
State the inheritance pattern for sickle cell anemia
- autosomal recessive inheritance
74
Describe the difference in inheritance between sickle cell trait and sickle cell disease
- needs to inherit both
- If only one is inherited - trait
- if both are inherited - disease
HbS
75
A patient with sickle cell anemia has which point mutations?
Glutamic acid is replaced by valine at position 6 of the beta chain
76
List the conditions of low oxygen tension that can lead to the sickling of red blood cells
low oxygen tension
- infection (anemic env - G6PD DEF, in HbS disease genetic mutation, in this case, causes sickling after infection)
- dehydration (stress)
- Hypoxia (stress)
77
Explain how the sickling of red blood cells can lead to autosplenectomy
- extravascular hemolysis
- spleen destroyed
- encapsulated organism - vaccinate patient
78
Explain how the sickling of red blood cells leads to vasoocclusive crises
- Sickled - polymerized RBC and looks like a sickle
- they tend to stick together
- other blood cells can't move past the cluster of cells
- block the vessels
- other RBCs can't pass-through
- tissues don't get oxygen
- pain - acute chest syndrome, dactylitis, priapism, stroke-like issues (carotid)
- head to toe - vasoocclusive crisis
- decreased oxygen to the tissues
79
Identify sickled red blood cells on a peripheral blood smear
- misshapen, sickle-shaped
- Howell- Jolly bodies - spleen involved
80
Which actions or conditions predispose HbS to polymerize?
Respiratory failure. dehydration, hypoxia, infection
81
The presence of small, round, basophilic inclusions in the erythrocytes of a patient with sickle cell anemia indicates...?
a non-functional spleen.
82
what are the signs or symptoms of a vaso-occlusive crisis?
Dactylitis. Autosplenectomy, Acute chest syndrome, Priapism
83
List the effects of vasoocclusive crises on different organ systems
- A pain crisis - microvascular ischemia causing severe pain
- 100% of SS patients have this symptom (homozygous - disease)
- need long-term narcotic treatment (risk of opioid consumption) - respiratory center in the brain is at risk
- Acute chest syndrome
- hypoxemia caused by microvascular disease of the lung
- stroke
- carotid affected
- auto splenectomy
- spleen dies due to increased extravascular hemolysis
- Howell-Jolly bodies indicate spleen involvement
- 100% SS auto splenectomy by adulthood
84
Name the organisms that a patient with autosplenectomy is most susceptible to
encapsulated
- strep pneumonia
- Haemophilus influenza
- klebsiella pneumonia
85
What is a vaso-occlusive crisis?
A pain crisis - microvascular ischemia causing severe pain
- 100% of HbS patients have this symptom
- need long-term narcotic treatment
86
List the complications of parvovirus and Salmonella species associated with sickle cell anemia
- aplastic crisis - Parvovirus B19 infection
- bone marrow shut down
- susceptible
- Salmonella causes osteomyelitis in patients with SS
- Osteomyelitis - caused by staph aureus, if stepped on a nail then by pseudomonas
87
Explain the different tests that can be done to diagnose sickle cell anemia
- screening E6V
- Sickle prep - peripheral blood sickles when exposed to sodium metabisulfite (reduces oxygen tension)
- Hb electrophoresis (HbA, Hb A/S, Hb SS)
88
Explain the findings on hemoglobin electrophoresis for sickle cell trait and sickle cell disease
- Hb electrophoresis (HbA, Hb A/S, Hb SS)
NORMAL
- HbA -97%
- HbA2 -2%
- HbF- 1%
here - Hb S
89
What is the most common pathogen responsible for osteomyelitis in patients with sickle cell disease?
Salmonella species
90
What is the mechanism of action of hydroxyurea in patients with sickle cell disease?
increases production of HbF
91
Treatment for homozygous patients?
- hydration
- hydroxyurea - create more HbF
92
Describe the percentages of the hemoglobin types found on hemoglobin electrophoresis for sickle cell trait and sickle cell disease
TRAIT:
- A2 = 2%
- S = 45%
- F = 1%
- A = 52%
- Anemia: none
DISEASE:
- A2 = 2%
- S = 90%
- F = 8%
- A = -
- Anemia: Normocytic
93
List different treatment options for sickle cell anemia
- Hydroxyurea - increases HbF
- Hydration
- bone marrow transplantation - reticulocytosis, parvovirus
- analgesics
94
Which of the following values represents a normal hemoglobin electrophoresis pattern?
Hemoglobin A, 97%; hemoglobin A2, 2%; hemoglobin F, 1%
95
Describe the role of pyruvate kinase in the glycolytic pathway
- Last enzyme in the process of converting glucose to pyruvate
- Phosphoenol pyruvate -> pyruvate
96
State the inheritance pattern of pyruvate kinase deficiency
- Autosomal recessive inheritance
97
Explain how pyruvate kinase deficiency can affect the oxygen dissociation curve
- Glycolytic enzyme is deficient -> results in extravascular hemolysis (misshapen RBC)
- Intrinsic disease
- Pyruvate is not created _> can't enter the Kreb's cycle
- Phosphoenol pyruvate increases ---- 1.3 Bisphosphoglycerate increases -----> 2,3 BPG increases
- Pathological increase of the release of oxygen from Haemoglobin
- Oxygen is released more easily
- There is a right shift in the oxygen dissociation curve
98
In RBCs, which intermediate substrate of the glycolytic pathway is directly responsible for altering the hemoglobin–oxygen dissociation curve?
2,3-Bisphosphoglycerate
99
Describe how a pyruvate kinase deficiency affects ATP and NADH levels
- RBC only uses glycolysis for energy (doesn't have mitochondria)
- In PK deficiency -> low amounts of ATP and NADH
- ATP can't be produced
- Pyruvate doesn't enter the kreb's cycle so NADH isn't produced
100
Explain how decreased NADH levels in pyruvate kinase deficiency can cause increased levels of methemoglobin
- NADH is necessary to convert Hb-Fe3+ (methemoglobin) to Fe2+ (ferrous iron)
- in the diet - Fe3+
- Cytochrome P reductase and NADH help to convert Ferric to the ferrous form of iron
- deficiency of NADH in pyruvate kinase deficiency
- the patient is in a state of methemoglobin (Hb - Fe3+)
101
Describe how a pyruvate kinase deficiency can affect the oxygen saturation curve
- 2,3 BPG increases
- right shift in the oxygen dissociation curve
102
What type of hemolysis do RBCs in pyruvate kinase deficiency undergo?
Extravascular hemolysis
- ATP deficiency causes problems in the Na/K ATPase, leading to osmotic instability and misshapen RBCs
103
Which of the following statements is FALSE?
NADH is used to convert iron from Fe3+ to Fe2+.
In pyruvate kinase deficiency, 2,3-BPG is increased.
The oxidation state of dietary iron that can be absorbed in the intestine is Fe3+.
Pyruvate kinase deficiency may result in methemoglobinemia.
The oxidation status of iron in hemoglobin is Fe2+.
The oxidation state of dietary iron that can be absorbed in the intestine is Fe3+.
We need Ferrous iron
104
Recognize the morphology of red blood cells in a patient with pyruvate kinase deficiency
- spiculated RBC
- needle-like projections coming out
105
State the expected methemoglobin levels in a patient with pyruvate kinase deficiency
- in a child (born with the deficiency)
- High methemoglobin levels due to lack of NADH
106
Identify echinocytes on a peripheral blood smear and state the cause of this morphology
- ATP deficiency has an effect on the Na/K ATPase pumps
- Echinocyes are formed
- Broken down by the spleen
107
List pathologies that can cause mechanical damage to red blood cells
- mechanical or stenotic heart valve (Waring Blender effect) - turbulent blood flow through the valve causes damage to the RBC
- Malignant hypertension - prothrombotic environment -> small clots in the small vasculature -> as RBCs try to pass through these small occluded vessels, they become misshaped and their cell walls are deformed and ultimately damaged.
108
List pathologies that can cause microthrombus formation
- diffuse microthrombus formation
- DIC - bleeding, platelet consumed, coagulation factors consumed, thrombi ---> causes normocytic, hemolytic microangiopathic anemia (extravascular hemolysis)
- HUS
- TTP
109
What is the term used to describe an RBC that is abnormal in shape due to mechanical shearing and destruction?
Schistocyte - helmet cell
110
Which conditions are the most likely causes of microangiopathic hemolytic anemia?
Disseminated intravascular coagulation
hemolytic uremic syndrome
thrombotic thrombocytopenic purpura
111
What are the typical lab findings seen in disseminated intravascular coagulation?
Low platelets, increased PT, increased PTT, increased bleeding time
112
What are the triggers for DIC?
- Acute Myelogenous Leukemia Type 3
- Amniotic fluid emboli
- Sepsis
- Venom (snake)
113
Recognize that red blood cell damage in microangiopathic hemolytic anemia is due to vascular defects in circulation
RBCs "shear" when they encounter vascular defects in circulation
- broken up or fragmented
- Schistocyte
- Helmet cells (nickname)
114
What type of abnormal RBCs are likely to be seen in the peripheral blood smear of a patient suspected to have disseminated intravascular coagulation?
Helmet cells
115
Identify schistocytes on a peripheral blood smear
- differentiate between sickle cell, bite cells (G6PD def)
- look like helmets
- Aortic valve stenosis
116
Explain the relationship between hemoglobinuria and iron deficiency anemia
- During hemolytic anemia - intravascular
- Hb + haptoglobin removed in urine
- Iron is also removed in this process
- leading to iron deficiency anemia
117
Recognize agglutination of red blood cells on a peripheral blood smear
118
List the 2 types of autoimmune hemolytic anemia
- Warm
- Cold
119
Explain how to differentiate between warm autoimmune hemolytic anemia and hereditary spherocytosis
- Coombs test
120
Which of the following microorganisms is associated with cold autoimmune hemolytic anemia?
Mycoplasma pneumoniae
