THE HAEMOLYTIC ANAEMIAS Flashcards by Iseoluwa Ojo

The life span of red blood cells is ____

120 days.

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Haemolytic disorders are conditions which lead to a reduction in the _______ of red cells .

mean lifespan

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↓in RBC lifespan →↑in rate of ________= compensated haemolytic state

erythropoiesis

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When lifespan of RBC falls to _____, erythropoiesis can no longer compensate hence haemolytic anaemia ensues

15days

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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

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HAEMOGLOBIN STRUCTURE

Hb molecule is a _____ of __ poly____ chains (globins),
A ______ molecule is attached to each globin chain.

tetramer; 4 ; peptide

haem

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Adult Hb consist of
____ __chains , each ___ amino acid long
__ ___chains, each ____ amino acid long

2 α; 141

2 β ; 146

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Hemolytic Anaemia Can be classified in several different ways:

Site of ______
Site of ______

destruction

defect

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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

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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

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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

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CAUSES of INTRACORPUSCULAR (INTRINSIC) hemolytic Anaemia:

Inherited defects:

_______ defects
________ defects
__________

Acquired defects
___________

Red cell membrane
Enzymatic
Hemoglobinopathies

Paroxysmal nocturnal hemoglobinuria (PNH)

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CAUSES of INTRACORPUSCULAR (INTRINSIC) hemolytic Anaemia:

Inherited defects
1. Red cell membrane defects
a. Hereditary _______
b. __________
c. Hereditary _______

spherocytosis

Pyropoikilocytosis

elliptocytosis

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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

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CAUSES of INTRACORPUSCULAR (INTRINSIC) hemolytic Anaemia:

Acquired defects
1. _____________

Paroxysmal nocturnal hemoglobinuria (PNH)

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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

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CAUSES of EXTRACORPUSCULAR (EXTRINSIC) hemolytic Anaemia :

_________ hemolytic anemias

__________ hemolytic anemias

Immune

Non- immune

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CAUSES of EXTRACORPUSCULAR (EXTRINSIC) hemolytic Anaemia

Immune hemolytic anemias
_________
________

Auto- immune
Allo-immune

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CAUSES of EXTRACORPUSCULAR (EXTRINSIC) hemolytic Anaemia

Non- immune

_______

________ agents

_______ processes
__________/_______

Infections

Physical

Microangiopathic

Splenic sequestration/hypersplenism

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Microangiopathic processes include:

___________ (DIC), __________ (TTP), ___________ (HUS), etc.

disseminated intravascular coagulations

thrombotic thrombocytopenia purpura

hemolytic uremic syndrome

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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)

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Paroxysmal Nocturnal Haemoglobinuria (PNH) is an (inherited or acquired?) disorder with an (intrinsic or extrinsic?) defect.

Acquired

Intrinsic

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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

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Iron binds to ______, returns to ______

Haem is broken down into _______

transferrin; marrow

excretable form

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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

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

In hereditary Elliptocytosis , Anaemia occurs T/F

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

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

G-6-Phosphate dehydrogenase deficiency is dominant T/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

Warm AI Hemolysis is more common in which gender?

Female

Warm AI Hemolysis is ____% idiopathic

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

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