W2: Haemolytic anaemia Flashcards
EASY ONE. What is haemolytic anaemia?
When the red blood cell destruction is so fast we losing RBC faster than we produce it.
RBC are destroyed before or after their normal life span?
Before lah omg. so the RBC is removed within 100 days.
What compensatory mechanism is expected when RBC is destroyed so quickly?
increase in marrow activity lah because we desperately need RBC.
There is heightened reticulocyte percentage (Reticulocytosis)
Name the two types of haemolysis
Intravascular and extravasular
Haptoglobin function?
A protein produced by liver to clear free haemoglobin from circulation
In intravascular haemolysis, RBC is broken down in circulation, increase free haemoglobin, increase haptoglobin. If too much hgb, then the __________
Excess free haemoglobin travels to the urogenital tract and filtered by glomerulus, passed out through urine.
Ferritin and iron together forms hemosiderin in renal tubule and passed out through urine. This is known as____________
Hemosiderinuria
Where does extravascular hemolysis happens?
In the reticuloendothelial system (liver, spleen and bone marrow)
Why is there no haemoglobinaemia or haemoglobinuria in extravascular haemolysis?
Because there is no haemolgobin released in the circulation`
Hyper_______ occurs in extravascular haemolysis
Hyperbilirubinaemia
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.
Heme and globin. Heme is further broken down in Fe and porphyrin. The porphyrin forms unconjugated bilirubin.
Renal failure, renal tubular dysfunction happens in _________
Haemoglobinuria
Splenomegaly and increase urinary urobilinogen happens in ____________
extravascular haemolysis
There is a _______ in serum lactate dehydrogenase for both haemolysis process
Increase, hence it is a marker for haemolysis
There is a decrease in _________ for both haemolysis process
serum haptoglobin
Examples of causes for hereditary haemolytic anemia
- hereditary spherocytosis
2, hereditary eliptocytosis
- G6PD deficiency
- Pyruvate kinase deficiency
- Genetic abnormalities in Hb.
Examples of causes for acquired haemolytic anemia
- Drug associated
- Autoimmune
- Alloimmune such as allografts, transfusion reactions
- Red cell fragmentation syndrome
- Malaria, clostridia
- secondary cause due to liver and renal disease
- Paroxysmal Nocturnal Hemoglobinuria
RBC destroyed prematurely by antibody and/or complement. What is this?
Immune related hemolytic anemia
Explain warm autoimmune haemolytic anaemia (AIHA).
- 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
Explain the 3 ways RBC are destroyed in warm AIHA.
- Macrophage express receptor for Fc region and trap and ingest the opsonized (with IgG) RBC. Leads to incomplete phagocytosis = spherocyte formation (weak, will lyse)
- Sequestered and phagocytosed by macrophages in spleen
- 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.
Clinical feature of warm AIHA include ______, jaundice, ________ sudden onset of severe anemia, fever.
Splenomegaly
Hepatosplenomegaly
Warm AIHA is normocytic, hypochromic anaemia. True or False?
FALSE LAH. Its normochromic, normocytic anaemia.
Complete blood count of warm AIHA is how?
Normal values all the way.
Special test for warm AIHA =
Direct antiglobulin test AKA direct Coombs test = detects sensitized RBC with IgG or C3b
warm AIHA patient is positive = RBC will agglutinate in test
Large_________ and _______ are found in full blood picture of warm AIHA.
Large polychromatic cells and spherocytes
Cold AIHA has optimum reaction of antibody with RBC at ______.
4 degree celsius.
Cold AIHA more common than WARM AIHA. True or False?
FALSE. Warm AIHA more common.
The antibody for warm AIHA = , for cold AIHA =
Warm = IgG
Cold = IgM
Primary cases of cold AIHA = idiopathic
Secondary cases of cold AIHA =
Infection, lymphoma, paroxysmal cold haemoglobinuria
Explain the process of cold AIHA
- IgM binds C1, initiate complement pathway
- C1 esterase activates C4 and C2, generating C3 convertase = cleavage of C3 to C3a and C3b.
- C3b is sequestered by macrophage of Kupffer cells in the liver
- Extravascular destruction of C3b coated erythrocytes.
- Some C3b will further activate C5, formation of membrane attack complex, leading to intravascular hemolysis.
As compared to warm AIHA, cold AIHA has a _______ jaundice
Milder jaundice
Patients with cold AIHA might get purplish/ bluish discolouration at the distal parts of the body. What is this called?
Acrocyanosis , happens due to interruption of blood flow in distal parts (fingers, toes).
Livedo reticularis is a clinical feature unique to cold AIHA. How does it look like?
purplish discolouration and lace like skin. Due to venous swelling caused by obstruction of the capillaries.
In cold AIHA, what are the expected findings for serum bilirubin, LDH and haptoglobin?
Increased bilirubin, increased LDH and decreased haptoglobin
For the blood smear of warm AIHA, the RBC are ______ distributed. For cold AIHA, it is _______.
warm = evenly distributed
cold = agglutination of RBC
Paroxysmal cold hemoglobinuria (PCH) mainly occurs to children after acute exposure to ________ infection or _______ infection.
upper respiratory tract infection and viral infection
Recurrent haemolysis following exposure to cold is what disease ______.
Paroxysmal cold hemoglobinuria (PCH)
For PCH, polyclonal cold reactive Ig-G antibodies bind to the RBC surface protein antigen but ________
will not agglutinate the erythrocytes.
PCH, a rare subtype of AIHA, is mediated by _________ antibody
Donath-Landsteiner antibody
If complement activation for PCH is at 37c, why the hell is it called “cold haemoglobinuria”?
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.
Complete the pathway for PCH:
- ____ binds to RBC surface proteins
- _________ fixed to RBC at _____ temp.
- optimum complement activation at 37c
- _______ complex activates the classical and terminal pathways , lead to haemolysis
IgG
Biphasic hemolysin at cold temp
P-anti-P complex
____________ is a special clinical feature of PCH. There is a discolouration in digits after exposure to cold or hot temps or even emotional stress.
Raynaud’s phenomenon
White = no blood flow Blue = no oxygen and vessels dilate Red = blood flow returns
Explain how Donath-Landsteiner test works
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.
