W2: Haemolytic anaemia

Question 1

EASY ONE. What is haemolytic anaemia?

Answer 1

When the red blood cell destruction is so fast we losing RBC faster than we produce it.

Question 2

RBC are destroyed before or after their normal life span?

Answer 2

Before lah omg. so the RBC is removed within 100 days.

Question 3

What compensatory mechanism is expected when RBC is destroyed so quickly?

Answer 3

increase in marrow activity lah because we desperately need RBC.

There is heightened reticulocyte percentage (Reticulocytosis)

Question 4

Name the two types of haemolysis

Answer 4

Intravascular and extravasular

Question 5

Haptoglobin function?

Answer 5

A protein produced by liver to clear free haemoglobin from circulation

Question 6

In intravascular haemolysis, RBC is broken down in circulation, increase free haemoglobin, increase haptoglobin. If too much hgb, then the __________

Answer 6

Excess free haemoglobin travels to the urogenital tract and filtered by glomerulus, passed out through urine.

Question 7

Ferritin and iron together forms hemosiderin in renal tubule and passed out through urine. This is known as____________

Answer 7

Hemosiderinuria

Question 8

Where does extravascular hemolysis happens?

Answer 8

In the reticuloendothelial system (liver, spleen and bone marrow)

Question 9

Why is there no haemoglobinaemia or haemoglobinuria in extravascular haemolysis?

Answer 9

Because there is no haemolgobin released in the circulation`

Question 10

Hyper_______ occurs in extravascular haemolysis

Answer 10

Hyperbilirubinaemia

Question 11

In extrvascular haemolysis, RBC is phagocytized by macrophage. The lysozyme degrades it into ______ and ______. ______ is further broken down into Fe and _______. The ______ forms unconjugated bilirubin which travels to the hepatocyte to become conjugated and goes into the biliary system.

Answer 11

Heme and globin. Heme is further broken down in Fe and porphyrin. The porphyrin forms unconjugated bilirubin.

Question 12

Renal failure, renal tubular dysfunction happens in _________

Answer 12

Haemoglobinuria

Question 13

Splenomegaly and increase urinary urobilinogen happens in ____________

Answer 13

extravascular haemolysis

Question 14

There is a _______ in serum lactate dehydrogenase for both haemolysis process

Answer 14

Increase, hence it is a marker for haemolysis

Question 15

There is a decrease in _________ for both haemolysis process

Answer 15

serum haptoglobin

Question 16

Examples of causes for hereditary haemolytic anemia

Answer 16

1. hereditary spherocytosis

2, hereditary eliptocytosis

3. G6PD deficiency
4. Pyruvate kinase deficiency
5. Genetic abnormalities in Hb.

Question 17

Examples of causes for acquired haemolytic anemia

Answer 17

1. Drug associated
2. Autoimmune
3. Alloimmune such as allografts, transfusion reactions
4. Red cell fragmentation syndrome
5. Malaria, clostridia
6. secondary cause due to liver and renal disease
7. Paroxysmal Nocturnal Hemoglobinuria

Question 18

RBC destroyed prematurely by antibody and/or complement. What is this?

Answer 18

Immune related hemolytic anemia

Question 19

Explain warm autoimmune haemolytic anaemia (AIHA).

Answer 19

• optimum reaction of antibody with RBC at 37c
• RBC coated with IgG or with complement
• Primary = no underlying disease
• Secondary = due to chronic lymphatic leukaemia, non-Hodgkin lymphoma, SLE , hypothyroidism

Question 20

Explain the 3 ways RBC are destroyed in warm AIHA.

Answer 20

1. Macrophage express receptor for Fc region and trap and ingest the opsonized (with IgG) RBC. Leads to incomplete phagocytosis = spherocyte formation (weak, will lyse)
2. Sequestered and phagocytosed by macrophages in spleen
3. complement protein C1 bind to RBC, activate classical complement pathway. C3b also come and attach. Then lastly kuppfer cell in liver in phagocytose this RBC.

Question 21

Clinical feature of warm AIHA include ______, jaundice, ________ sudden onset of severe anemia, fever.

Answer 21

Splenomegaly

Hepatosplenomegaly

Question 22

Warm AIHA is normocytic, hypochromic anaemia. True or False?

Answer 22

FALSE LAH. Its normochromic, normocytic anaemia.

Question 23

Complete blood count of warm AIHA is how?

Answer 23

Normal values all the way.

Question 24

Special test for warm AIHA =

Answer 24

Direct antiglobulin test AKA direct Coombs test = detects sensitized RBC with IgG or C3b

warm AIHA patient is positive = RBC will agglutinate in test

Question 25

Large_________ and _______ are found in full blood picture of warm AIHA.

Answer 25

Large polychromatic cells and spherocytes

Question 26

Cold AIHA has optimum reaction of antibody with RBC at ______.

Answer 26

4 degree celsius.

Question 27

Cold AIHA more common than WARM AIHA. True or False?

Answer 27

FALSE. Warm AIHA more common.

Question 28

The antibody for warm AIHA = , for cold AIHA =

Answer 28

Warm = IgG

Cold = IgM

Question 29

Primary cases of cold AIHA = idiopathic

Secondary cases of cold AIHA =

Answer 29

Infection, lymphoma, paroxysmal cold haemoglobinuria

Question 30

Explain the process of cold AIHA

Answer 30

1. IgM binds C1, initiate complement pathway
2. C1 esterase activates C4 and C2, generating C3 convertase = cleavage of C3 to C3a and C3b.
3. C3b is sequestered by macrophage of Kupffer cells in the liver
4. Extravascular destruction of C3b coated erythrocytes.
5. Some C3b will further activate C5, formation of membrane attack complex, leading to intravascular hemolysis.

Question 31

As compared to warm AIHA, cold AIHA has a _______ jaundice

Answer 31

Milder jaundice

Question 32

Patients with cold AIHA might get purplish/ bluish discolouration at the distal parts of the body. What is this called?

Answer 32

Acrocyanosis , happens due to interruption of blood flow in distal parts (fingers, toes).

Question 33

Livedo reticularis is a clinical feature unique to cold AIHA. How does it look like?

Answer 33

purplish discolouration and lace like skin. Due to venous swelling caused by obstruction of the capillaries.

Question 34

In cold AIHA, what are the expected findings for serum bilirubin, LDH and haptoglobin?

Answer 34

Increased bilirubin, increased LDH and decreased haptoglobin

Question 35

For the blood smear of warm AIHA, the RBC are ______ distributed. For cold AIHA, it is _______.

Answer 35

warm = evenly distributed

cold = agglutination of RBC

Question 36

Paroxysmal cold hemoglobinuria (PCH) mainly occurs to children after acute exposure to ________ infection or _______ infection.

Answer 36

upper respiratory tract infection and viral infection

Question 37

Recurrent haemolysis following exposure to cold is what disease ______.

Answer 37

Paroxysmal cold hemoglobinuria (PCH)

Question 38

For PCH, polyclonal cold reactive Ig-G antibodies bind to the RBC surface protein antigen but ________

Answer 38

will not agglutinate the erythrocytes.

Question 39

PCH, a rare subtype of AIHA, is mediated by _________ antibody

Answer 39

Donath-Landsteiner antibody

Question 40

If complement activation for PCH is at 37c, why the hell is it called “cold haemoglobinuria”?

Answer 40

Because in order for PCH to happen, cold exposure has to happen FIRST for antibody to bind. then only at 37c it will activate complement.

Question 41

Complete the pathway for PCH:

1. ____ binds to RBC surface proteins
2. _________ fixed to RBC at _____ temp.
3. optimum complement activation at 37c
4. _______ complex activates the classical and terminal pathways , lead to haemolysis

Answer 41

IgG

Biphasic hemolysin at cold temp

P-anti-P complex

Question 42

____________ is a special clinical feature of PCH. There is a discolouration in digits after exposure to cold or hot temps or even emotional stress.

Answer 42

Raynaud’s phenomenon

White = no blood flow
Blue = no oxygen and vessels dilate
Red = blood flow returns

Question 43

Explain how Donath-Landsteiner test works

Answer 43

So two sample will be preincubated at 4c and 37c each. After that both samples will be exposed to 37c. Haemolysis should occur at the 4c tube.