THE HAEMOLYTIC ANAEMIAS Flashcards
The life span of red blood cells is ____
120 days.
Haemolytic disorders are conditions which lead to a reduction in the _______ of red cells .
mean lifespan
↓in RBC lifespan →↑in rate of ________= compensated haemolytic state
erythropoiesis
When lifespan of RBC falls to _____, erythropoiesis can no longer compensate hence haemolytic anaemia ensues
15days
Haemolytic anaemia is therefore a form anaemia due to increased (premature) ___________, either in the ________(___) or _________(____) for which the ______ cannot compensate.
destruction of red blood cells (RBCs)
blood vessels (intravascular haemolysis)
elsewhere in the human body (extravascular)
marrow
HAEMOGLOBIN STRUCTURE
Hb molecule is a _____ of __ poly____ chains (globins),
A ______ molecule is attached to each globin chain.
tetramer; 4 ; peptide
haem
Adult Hb consist of
____ __chains , each ___ amino acid long
__ ___chains, each ____ amino acid long
2 α; 141
2 β ; 146
Hemolytic Anaemia Can be classified in several different ways:
Site of ______
Site of ______
destruction
defect
Hemolytic Anaemia Can be classified in several different ways:
Site of destruction*:
•_________ HA
•_________ HA
Site of defect**:
• __________ (______) defect
• _________ (_____) defect
Extravascular
Intravascular
Intracorpuscular; intrinsic
Extracorpuscular; extrinsic
Hemolytic Anaemia Can be classified in several different ways:
Site of destruction*:
• Extravascular HA: premature destruction of RBC by ______ in the _______
• Intravascular HA: haemolysis occur mainly in the _______
macrophages: Reticuloendothelia system (RES)
circulation
Hemolytic Anaemia Can be classified in several different ways:
Site of defect**:
• Intracorpuscular (intrinsic) defect: structural or functional defect ____ the RBC
• Extracorpuscular (extrinsic) defect: caused by abnormality in RBC’s _______
within
environment
CAUSES of INTRACORPUSCULAR (INTRINSIC) hemolytic Anaemia:
Inherited defects:
_______ defects
________ defects
__________
Acquired defects
___________
Red cell membrane
Enzymatic
Hemoglobinopathies
Paroxysmal nocturnal hemoglobinuria (PNH)
CAUSES of INTRACORPUSCULAR (INTRINSIC) hemolytic Anaemia:
Inherited defects
1. Red cell membrane defects
a. Hereditary _______
b. __________
c. Hereditary _______
spherocytosis
Pyropoikilocytosis
elliptocytosis
CAUSES of INTRACORPUSCULAR (INTRINSIC) hemolytic Anaemia:
Inherited defects:
Enzymatic defects
a. _____ pathway defects – _______ deficiency, etc.
b.______ pathway defects: ______ deficiency
Glycolytic; pyruvate kinase
Pentose; G- 6-PD
CAUSES of INTRACORPUSCULAR (INTRINSIC) hemolytic Anaemia:
Acquired defects
1. _____________
Paroxysmal nocturnal hemoglobinuria (PNH)
CAUSES of INTRACORPUSCULAR (INTRINSIC) hemolytic Anaemia:
Inherited defects: Hemoglobinopathies
a. Qualitative defects – ______ disease , _______ disease, _______ disease, etc.
b. Quantitative defects – _______
sickle cell
HB C
HB E
thalassemias
CAUSES of EXTRACORPUSCULAR (EXTRINSIC) hemolytic Anaemia :
_________ hemolytic anemias
__________ hemolytic anemias
Immune
Non- immune
CAUSES of EXTRACORPUSCULAR (EXTRINSIC) hemolytic Anaemia
Immune hemolytic anemias
_________
________
Auto- immune
Allo-immune
CAUSES of EXTRACORPUSCULAR (EXTRINSIC) hemolytic Anaemia
Non- immune
_______
________ agents
_______ processes
__________/_______
Infections
Physical
Microangiopathic
Splenic sequestration/hypersplenism
Microangiopathic processes include:
___________ (DIC), __________ (TTP), ___________ (HUS), etc.
disseminated intravascular coagulations
thrombotic thrombocytopenia purpura
hemolytic uremic syndrome
CLASSIFICATION OF HAEMOLYTIC ANAEMIA (HA)-
Inherited or acquired
– Typically, inherited disorders are caused by __________ defect
– Acquired haemolytic disorders are caused by ____________ factors
– Exceptions include:
________________
intrinsic (intracorposcular)
extrinsic (extracorpuscular)
Paroxysmal Nocturnal Haemoglobinuria (PNH)
Paroxysmal Nocturnal Haemoglobinuria (PNH) is an (inherited or acquired?) disorder with an (intrinsic or extrinsic?) defect.
Acquired
Intrinsic
Pathways of RBC Destruction: Extravascular
RBCs phagocytized by _____ cells
RBC ______ is broken down
Hemoglobin broken into ___________
___________ are recycled.
Reticuloendothelial
membrane
haem, iron and globin
Globin and iron
Iron binds to ______, returns to ______
Haem is broken down into _______
transferrin; marrow
excretable form
Pathways of RBC Destruction: Extravascular
Most hemoglobin degradation occurs within the ______ of the ____.
_____________ portions are conserved and reutilized.
Heme is reduced to _______, eventually degraded to _______, and excreted in the ____.
Thus, indirect indicators of erythrocyte destruction include the ______ level and _______ concentration in the _____.
macrophages; spleen
The globin and iron
bilirubin; urobilinogen; feces
blood bilirubin
urobilinogen; urine
Heme breakdown
Heme is (oxidized or reduced?) to ______ by _______ which is (oxidized or reduced?) by ______ to water (soluble or insoluble?) indirect ______ (conjugated or unconjugated?) which then binds to _____
Oxidized; biliverdin; heme oxygenase
Reduced; biliverdin reductase
Insoluble ; bilirubin; unconjugated
albumin
Indirect bilirubin is conjugated in the ____ by __________ to direct bilirubin which is water (soluble or insoluble?) capable of
______ and _____ excretion.
liver
glucoronly transferase
Soluble
biliary and renal
Haemolysis leads to excess production of bilirubin but within livers ability to conjugate
T/F
F
Beyond it
High plasma concentrations of unconjugated bilirubin (normal concentration ~ _____ mg/dL)
0.5
Pathways of RBC Destruction: intravascular
Free hemoglobin binds to _____ and is then (oxidised or reduced?) to ________ which binds to
–__________
– ________ :.
These proteins are cleared by the _____ where the heme is broken down to recover iron & produce bilirubin.
haptoglobin
Oxidized; methhemoglobin
hemopexin; albumin
liver
Methemoglobin + albumin = ______
methemalbumin
Pathways of RBC Destruction: intravascular
When the erythrocyte is destroyed within the vascular system, hemoglobin is released (directly or indirectly ?) into the ___. Normally, the free hemoglobin quickly complexes with _______, and the complex is degraded in the _____.
In severe hemolytic states, _____ can become depleted, and free hemoglobin dimers are __________
Additionally, with ______ depletion, some hemoglobin is quickly oxidized to _______ and bound to either _______ or _______ for eventual degradation in the liver.
Directly; blood
haptoglobin; liver
haptoglobin; filtered by the kidney.
haptoglobin; methemoglobin
hemopexin or albumin
CLINICAL FEATURES OF HAEMOLYTIC STATES
•Evidence of increased red cell destruction
–_______
–______
jaundice
pallor
CLINICAL FEATURES OF HAEMOLYTIC STATES
•Presence of ______ stones In chronic haemolytic states
•_______
•Expansion of _______ in (congenital or Acquired?) HA
– Frontal & parietal bossing
Pigment
Splenomegaly
marrow cavities
Congenital
EVIDENCE OF HAEMOLYSIS-
LABORATORY
Biochemical consequences of haemolysis
– Hyper_____________ (____jugated)
– Reduced ________
bilirubinaemia; unconjugated
serum haptoglobin
EVIDENCE OF HAEMOLYSIS-
Morphology:
Evidence of damaged red cells.
–_________, red cell ____,
________cells.
Evidence of increased red cell production
–________
– _______ red cells
Reduced red cell span
–____________ (____)
Micro-spherocyte; fragments; sickle
Polychromasia; Nucleated
Radioactive chromium (51Cr )
EVIDENCE OF HAEMOLYSIS-
CLINICAL:
______
______
jaundice
anaemia
EVIDENCE OF HAEMOLYSIS-
Intravascular haemolysis:
_________
Reduced serum __________
_______uria
________uria
Reduced _______ levels
_____________emia
Haemoglobinaemia
haptoglobulin
Haemoglobin
Haemosiderin
haemopexin
Methaemalbumina
Methaemalbuminaemia is tested for by the __________ test
Schumm’s
LABORATORY EVIDENCE OF
INCREASED ERYTHROPOIETIC ACTIVITY
•Peripheral blood:
-_________(polychromasia) and _________(nucleated red blood cells)
-_________ : high MCV
Reticulocytosis; erthroblastaemia
Macrocytosis
LABORATORY EVIDENCE OF
INCREASED ERYTHROPOIETIC ACTIVITY
•Bone marrow
-Erythroid ______
–Reduced _______/____ ratio
•Bone
Changes in the ______ and _____ bones
hyperplasia
myeloid/erythroid
skull and tubular
In extravascular hemolytic Anaemia, how is the :
Routine blood film
Reticulocyte count
Bone marrow examination
Bilirubin state in plasma or serum
Haptoglobulin levels in plasma or serum
Plasma hemoglobin
Polychromatophilia
Increased
Erythroid hyperplasia
Unconjugated
Reduced or absent
N or increased
In intravascular hemolytic Anaemia, how is the :
Routine blood film
Reticulocyte count
Bone marrow examination
Bilirubin state in plasma or serum
Haptoglobulin levels in plasma or serum
Plasma hemoglobin
Polychromatophilia
Increased
Erythroid hyperplasia
Unconjugated
absent
Very increased
Presence of the following in the urine of a patient with intravascular hemolytic Anaemia
Bilirubin
Hemosiderin
Hemoglobin
No
Yes
Yes in severe cases
Presence of the following in the urine of a patient with extravascular hemolytic Anaemia
Bilirubin
Hemosiderin
Hemoglobin
No
No
No
COMPLICATIONS of hemolytic Anaemia
________ crisis
_________ in chronic haemolytic states
Aplastic
Leg ulcers
TREATMENT of hemolytic Anaemia
Treat ____________
Give ________ especially in chronic haemolytic anaemia
May___________ in severe forms
the underlying cause
folic acid
require red cell concentrates
RED CELL MEMBRANE Structure
___laminar, _____- dimensional
Outermost layer:______,_____
Central layer: _______,_______
Inner layer: _______
Tri; three
glycolipids, glycoproteins
cholesterol, phospholipids
cytoskeleton
Hereditary sperocytosis
Defined as a group of hemolytic Anaemia characterized by the presence of (sparse or dense?), ______ shaped red cells without _____
Dense
spherically
central pallor
Hereditary sperocytosis
The _________ renders it susceptible to premature removal by the _____
abnormal cell shape
spleen
Most common congenital HA is ??
Hereditary sperocytosis
Incidence of Hereditary sperocytosis is ????
1 in 5000
Hereditary sperocytosis
Which is more severe between the autosomal dominant and autosomal recessive strain and by how much
autosomal recessive
25%
Hereditary sperocytosis can be missed till adulthood
T/F
T
In Hereditary sperocytosis l, Haemolysis is confined to the _____ and hence ____vascular
spleen
Extra
MEMBRANOPATHY: Hereditary Spherocytosis
Complications:
- ______ crisis
- ________ anaemia
- _______ crisis
-________itis
-_________iasis
-_________
Aplastic
Megaloblastic
Haemolytic
Cholecyst
Cholelith
Severe
MEMBRANOPATHY: Hereditary Spherocytosis
Differentials:
______ haemolytic anaemia
______ injury
_________reactions
hyper______
Immune
Thermal
Haemolytic transfusion
splenism
Management of Hereditary Spherocytosis
– _______ 5mg weekly, ______ life long
– _________ in severe or complicated forms
–________ in severe hemolytic crisis
Folic Acid; prophylaxis
Splenectomy
Blood transfusion
Hereditary Elliptocytosis is often symptomatic
T/F
F
Often aymptomatic(85%)
In hereditary Elliptocytosis there is usually no splenomegaly
T/F
T
In hereditary Elliptocytosis , Anaemia occurs
T/F
T
Hereditary Elliptocytosis
Has 5 clinical syndromes:
_______
_____
______
______
______
slet carrier, common hemolytic Anaemia , HPP, spherocytic elliptocytosis and southeast Asian ovalocytosis
most common enzyme defect of hemolytic Anaemia is ?
ENZYMOPATHY- G-6-Phosphate dehydrogenase deficiency
ENZYMOPATHY- G-6-Phosphate dehydrogenase deficiency incidence is almost __% of the world’s population
1
2 types of Normal G6PD enzyme
Most prevalent world wide is designated ___
About __% of healthy _______ have type __. Which has Normal enzyme activity
B
20
Africans
A
G-6-Phosphate dehydrogenase deficiency is X linked
T/F
T
G-6-Phosphate dehydrogenase deficiency is dominant
T/F
F
G-6-Phosphate dehydrogenase deficiency
More common in males or females?
Males
G-6-Phosphate dehydrogenase deficiency
The most common abnormal variant is the _____ type, designated ——–
– It is found in __% ____
– Enzyme activity is reduced to
About ____% of normal
African
A
10; blacks
10
G-6-Phosphate dehydrogenase deficiency
Less common abnormal variant is the ______ type,
– Enzyme activity is reduced to ____%
Mediterranean
1- 3
G-6-Phosphate dehydrogenase deficiency
Pathophysiology
– Red cell is protected from oxidative damage by constant regeneration of ____________ through the ________ cycle
-The continuous supply of ______ required to drive the ______ pathway is provide by the _________ pathway
reduced glutathione(GSH) via the glutathione cycle
NADPH; Hexose monophospshate
G-6-Phosphate dehydrogenase deficiency
Patterns of haemolysis
– Chronic _________ HA
Life-long decompensated HA of variable severity which does not respond to ______
Non-spherocytic
splenectomy
G-6-Phosphate dehydrogenase deficiency
Patterns of haemolysis
Episodic Haemolysis
• (More or Less ?) common presentation
• Acute haemolys is induced by increased _________- usually ____vasular Haemolysis
More
oxidant stress
Intra
G-6-Phosphate dehydrogenase deficiency
• Triggers of acute haemolysis
– ______
–_____ beans- aaaaa
-_______
Drugs
Fava; favism
infections
Triggers of acute hemolysis
Fava beans- favism
• Associated only with the ______ variance
Mediterranean
• Most common cause of neonatal jaundice is ????
G-6-Phosphate dehydrogenase deficiency
G6PD enzymes —activity—source
B
A
A-
M
100; widespread
90; blacks
8-20; blacks
0-7; Mediterranean whites
Laboratory features of G6PD
–______
– ____ cells
-_____ bodies
Anisocytosis
Bite
Heinz
IMMUNE HAEMOLY TIC ANAEMIA
Autoimmune HA:
• _________ hemolytic anemia
•_______ hemolytic anemia •
•____-induced IHA
Warm autoimmune
Cold autoimmune
Drug
IMMUNE HAEMOLY TIC ANAEMIA
Autoimmune HA:
• Warm autoimmune hemolytic anemia
(Idiopathic, Secondary : ______ disorders, ______ diseases)
Lymphoproliferative; autoimmune
IMMUNE HAEMOLY TIC ANAEMIA
Autoimmune HA:
• Cold autoimmune hemolytic anemia
-__________ syndrome
- _______________
Cold agglutinin
Paroxysmal cold hemoglobinuria
Cold autoimmune hemolytic anemia
Cold agglutinin syndrome
• (Idiopathic, Secondary- _____, ________, LPD)
• Paroxysmal cold hemoglobinuria (Idiopathic, Secondary- _____,_____,_____)
mycoplasma; infectious mono
measles, mumps, syphilis
IMMUNE HAEMOLY TIC ANAEMIA
Alloimmune HA
• As ________ reactions
blood transfusion
Warm AI Hemolysis
Can occur at all age groups
T/F
T
Warm AI Hemolysis is more common in which gender?
Female
Warm AI Hemolysis is ____% idiopathic
50
Cold AI Hemolysis
– Usually Ig ___
– Acute or Chronic form
– Chronic:
•C/F:
–______ patients
–____, ____ & often ___ fingers, toes, ears, or nose (_____)
•Inv:
– e/o hemolysis
– P Smear: Micro-spherocytosis
– Ig __ with specificity to ___ or ____
M
Elderly
Cold; painful; blue ; Acrocyanosis
M; I ; I Ag
•
Treatment of Cold AI Hemolysis
– Treatment of the ______
– Keep _______
–_____ treatment
– Blood ______
underlying cause
extremities warm
Steroids
transfusion
Treatment of Warm AI hemolysis
– Correct the underlying cause
–______ 1mg/kg po until Hb reaches ___mg/dl then taper slowly and stop
– ________: for life threatening problems
– If no response to steroids , try _______ or,
–__________: Azathioprine, Cyclophosphamide
Prednisolone
10
Transfusion
Splenectomy
Immunosuppressive
NON IMMUNE HA
__________ to red cells
Drugs
______
Infections
Hyper______
Mechanical trauma
Burns
splenism
NON IMMUNE HA
Mechanical trauma to red cells:
-Abnormalities in ________
- ______________
-_____________ HA
heart and large vessels
March haemoglobinaemia
Microangiopathic
NON IMMUNE HA
Mechanical trauma to red cells
•
Abnormalities in heart and large vessels
–
•
–
•
March haemoglobinaemia Burns
Aortic valve prostheses, coarctation of aorta Microangiopathic HA
Haemolytic uremic syndrome, thrombotic thrombocytopenia, disseminated intravascular haemolysis
–
•
• •
• Drugs
Infections
•
Malaria, clostridium perfringens
Hypersplenism
Cold IHA; Warm IHA
AGE
Ig
Temperature
40-80; all age
M; G
3-4; normal body
In cold, _____ clumps and activates _____
Rbc
IgM
Dacrocyte is to ________ as drepanocyte is to _________
Myelofibrosis
Sickle cell
Coombs test is positive in ????
Immune hemolytic Anaemia
In G6PD deficiency
Favism is common in blacks of African Decent
T/F
F
In G6PD deficiency
Morphologic findings include Heinz bodies, Blister Cell and bite cells
T/F
F
No blister cells
Coomb’s tests is positive in only _____ Anaemia
Immune hemolytic
Hb C disease is a genetic blood disorder that affects ______, a protein in red blood cells that carries oxygen. It is caused by a mutation in the ____ gene
In Hb C disease, the mutation results in the production of an abnormal hemoglobin called hemoglobin C. Hemoglobin C is _______ at carrying oxygen than normal hemoglobin (hemoglobin ___), which can lead to mild to moderate anemia.
hemoglobin
HBB
less efficient
A
Thrombotic thrombocytopenic purpura (TTP)
caused by a deficiency or dysfunction of an enzyme called ______, which is responsible for _______ called _______.
Without this enzyme, VWF can accumulate in the blood vessels and form blood clots, which can block the flow of blood to organs and tissues.
ADAMTS13
breaking down a protein
von Willebrand factor (VWF)
TTP is more common in which gender
Women
hemolytic uremic syndrome
In all cases, HUS is characterized by the destruction of _______, the formation of _________, and ______ damage.
red blood cells (hemolysis)
blood clots in small blood vessels (thrombosis)
kidney
Non-megaloblastic macrocytosis:
This type of macrocytosis is characterized by ____ red blood cells with _____ nuclei.
It can be caused by a variety of factors, including ____ disease, _______,_______ , certain medications (such as chemotherapy drugs), and ________ syndromes
large; normal
liver
alcoholism, hypothyroidism
myelodysplastic
______ cells are seen in microandiopathic haemolysis
_________ are seen in autoimmune haemolysis
_________ are seen in hereditary spherocytosis
Fragment
Microspherocytes
Microspherocytes
Presence of spherocytes in hemolysis caused by hereditary enzymopathies
T/F
F
