haemolytic anaemia Flashcards
what is meant by ‘haemolysis’?
- Premature attack and destruction of erythrocytes (<120
days) – haemolysis - Detectable drop in the measured haemoglobin (anaemia)
- Erythrocytes can either have an intrinsic defect
(hereditary) or are otherwise healthy and attacked
(acquired
how do we classify haemolytic anaemia by location?
Extravascular
Intravascular
what are the two causes of haemolytic anaemias
- hereditary
- acquired
what are the hereditary causes of haemolytic anaemia?
Problems with :
Membrane → Hereditary Spherocytosis (Hereditary elliptocytosis)
Metabolism→G6PD
(PKD and Embden- Meyerhof pathway defects)
Haemoglobinopathies → (Thalassemia
& Sickle Cell Disease)
what are the acquired causes of haemolytic anaemia?
Antibodies production causes RBC to be attached→ Autoimmune: Warm, mixed and cold
Alloimmune: Transfusion reaction/HDN
Drug Induced
Infections
Explain the normal Membrane structure and it’s importance
The erythrocyte membrane is asymmetrical
The lipid bilayer is anchored to a network of cytoskeletal proteins via transmembrane proteins such as:
- Band 3 (Most abundant)
- Phospholipid bilayer
- Alpha and Beta spectrin
- Ankyrin
•This network on the inner surface of membrane proteins provides shape, strength and flexibility to the membrane
(So they don’t get trapped/burst can deal with pressure)
Hereditary Spherocytosis is an example of what type of haemolysis
extravascular haemolysis
what type of membrane defect is caused in hereditary spherocytosis and what are the effects
> Autosomal dominant (75%)
> deficiency in Membrane proteins which can affect/ impair the overall interactions and network => loss of RBC membrane as it peels away which results in spherocytes
> Spherocytes Reduced SA:V ratio
Sequestered and destroyed in the
spleen (extravascular haemolysis) by macrophages
what are the symptoms of hereditary spherocytosis?
- Jaundice (elevated levels of bilirubin
- Anaemia (tired, pale)
- enlarged spleen
what tests are run in the case of hereditary spherocytosis
Whole blood (K-EDTA) (purple)
Serum (SST) (biochem assay to look for markers) (yellow )
Urine
what is the transport time for a HS sample?
< 4 hurs
what temperature should HS sampke ve kept /stored at
4 °C
what does a HS FBC show
what will a blood film show for HS
what will a direct antiglobulin test show for HS
direct antiglobulin tests for the presence of antibodies coating RBC
no antibodies => -ve result
what biochemical test are performed for HS
Test- There are several causes of jaundice in neonates, so other causes should be excluded.
Result => elevated unconjugated bilirubin
serum aminotransferases
Test - Performed in the presence of jaundice.
Usually normal in HS but may be deranged with intercurrent viral infection.
Result=> usually normal
what will an EMA binding test show in HS
what treatment is provided in cases of HS
Folate Therapy
* Moderate-Severe HS
2. Splenectomy
* Effective at reducing haemolysis
* Increased risk of sepsis by encapsulated bacteria
what is the warm classification of Autoimmune Haemolytic Anaemia?
- 80-90% of AIHA
- Warm-reactive IgG antibodies that bind optimally at 37 °C
- IgG with or without complement
- Removed by MØ of the RES (extravascular = macrophages of reticular endometrium haemolysis)
what is the mixed classification of Autoimmune Haemolytic Anaemia?
5% of AIHA
Warm IgG and cold IgM
what is the cold classification of Autoimmune Haemolytic Anaemia?
10% of AIHA
- Cold-reactive IgM antibodies which Bind optimally at 4 °C
-IgM potent activators of complement
- Intravascular (due to the action of Igm and compliment (puncture holes in RBC)) & Extravascular (macrophages - RBC destruction)
what are the symptoms of warm AIHA?
Anaemia
Mild splenomegaly
Jaundice (RBC breakdown so more bilirubin present)
Secondary AIHA
what are the symptoms of cold AIHA?
Anaemia
Mild splenomegaly
Jaundice (RBC breakdown so more bilirubin present)
Raynaud’s Phenomenon
what specimen tests are carried out for AIHA
Whole blood (K-EDTA)
* Serum separation tube
* Rust top tube
* Urin
what is the transport time frame / storage temperature for sample
Transport <4h
* Refrigeration, 4 °C if necessary
what will a FBC show for WARM AIHA
what will a blood film show for WARM AIHA
how is warm AIHA diagnosed using a direct antiglobulin test?
blood taken in in purple tube
what will a cold AIHA blood film look like
how is cold AIHA diagnosed using a direct antiglobulin test?
what treatment is provided for warm AIHA
- Corticosteroids (e.g. prednisolone first-line treatment )
- Splenectomy – second line - damaged cells can continue to carry oxygen
- Monoclonal antibodies e.g. rituximab (anti-CD20)
- Treat the secondary cause
- Immunosuppressants
- Blood transfusion and/or Folic acid– severe case
what treatment is provided in cold AIHA
- Stay warm! - avoid the cold
- Monoclonal antibodies e.g. rituximab
- Treat the secondary cause
- Blood transfusion and/or Folic acid– severe cases
Define haemolytic anaemia of a newborn
A condition where the RBCs of the foetus or neonates are destroyed by immunoglobulin G (IgG) antibodies produced by the mother
What are the two mechanisms of HDN?
Mechanism (1)- Antibody Adsorption
Mechanism (2)- Foetal-Maternal haemorrhage (FMH)
describe the Antibody Adsorption mechanism
A foetus is immunised when the mother’s antibodies enter the baby’s circulation through the placenta.
The foetus absorbs the mother’s immunoglobulin towards the end of the pregnancy as a protective mechanism
Passage of maternal IgG can cause lysis of foetal cells
What is Foetal-maternal Haemorrhage (FMH) in relation to first pregnancy
Rh - mother but father Rh + so child is Rh+
FMH occurs due to blood mixing during:
• Labor/delivery
• Rht blood being transfused to mum
• Ruptured ectopic pregnancy
• Placental abruption
• Abortion (spontaneous or elective)
• During 3rd trimester. absent cytotrophoblast of placenta
How does the body respond to FMH first pregnancy
The mothers body’s recognises the antibodies as non self and become sensitised so antibodies are formed to fight Rh+ cells. In first pregnancy mother produces ITM antibodies which don’t cross the placenta wall so baby not harmed
How does the body respond to FMH second pregnancy
In second pregnancy maternal IgG antibodies quickly form and recognise fetal cells as foreign and attack causing haemolysis as RBCs
Pathologies if the second pregnancy
Antibodies from the mother Diffuse through the placenta into a fetus; an Attachment phase where antigens on the RBC attach to the antibodies then Agglutinationoccurs when RBC and agglutinant form a bond. These macrophages produce lytic enzymes to destroy RBCs causing Lysis. Phagocytosis FC receptor of immunoglobulin on spleen and macrophages recognises the FC portion of agglutinates causing haemolysis
** UCB (unconjugated bilirubin)** through macrophages being converted to CB(conjugated bilirubin) causing Extramedullary Hematopoiesis as bone morrow overworked
Summarise the Pathogenesis
what are the clinical presentations of HDN
Pale/yellow skin
Mild Jaundice
Urine discolouration
Splenomegaly
Hepatosplenomegaly
Hydrops fetalis
Kernicterus
Kernicterus – (Bilirubin Encephalopathy)
Discuss Hydrops Fetalis
What laboratory Testing is done in HDN
- Maternal group antibody screen if anaemia is suspected then:
- FBC on baby
- ABO and Rh (D) typing of all babies born to a Rh(D)- mother.
- If baby group is Rh(D)- no further action.
- If baby group is Rh(D)+ a Kleihauer test is performed.
- Direct Agglutination Testing (DAT) - on foetal cells to detect bound antibody
what is the timing of the screening
what do the results for FBC And Blood Film show
Low HB
Low Hct
High reticulocytes (this may increase MCV)
High LDH
High unconjugated bilirubin
Low haptoglobin
Low albumin
discuss a Direct Coombs test
Detects maternal anti-D antibodies that have already bound to fetal RBCs.
The anti-IgG binds “directly” to the maternal anti-D IgG that coats fetal RBCs in HDN.
what is the Direct Coombs test used for
diagnoses HDN
what test is used in the prevention of HDN
Indirect Coombs test
Discuss the indirect Coombs test
Detects anti-D antibodies in the mother’s serum.
If these were to come into contact with fetal RBCs they would hemolyse them and hence cause HDN.
describe the Laboratory Testing- Kleihauer – Betke Acid Elution Test
what are the results of Kleihauer – Betke Acid Elution Test
FMH Quantification by Flow Cytometry
How Anti-D prophylaxis works-prevention in unsensitised mother
ABO incompatibility in HDN
HDN occurs when a mother with blood group O becomes pregnant with a foetus with different blood types A, B or AB
ABO antibodies are naturally occurring antibodies that are clinically significant
ABO caused HDN commonly occurs but is less severe
what are the Clinical features OF ABO HDN
what are the Lab diagnosis of ABO HDN
What are some of the other causes of HDN
Anti-E
(second most common, mild disease)
Anti-c
(third most common, leads to mild to severe)
Anti C and anti E (rare)
Antibody combination
(anti- C and anti- E occurring together can be severe)
Other antibodies
Kell system antibodies (uncommon causes)
Duffy, MNSs and Kidd system antibodies (rare causes)
Lewis and P system antibody no occurrence in HDN
discuss HDN caused by anti-E
Anti-E is an antibody that can cause hemolytic disease of the newborn (HDN) when it is present in the mother’s blood and crosses the placenta to attack the baby’s red blood cells. The severity of HDN depends on the amount of anti-E antibody in the mother’s blood and the baby’s blood type.
The treatment for HDN depends on the severity of the condition. In mild cases, the baby may not require any treatment and the condition will resolve on its own. In more severe cases, the baby may require phototherapy, which involves exposing the baby’s skin to a special light that helps break down the bilirubin in the blood. In some cases, the baby may require a blood transfusion to replace the damaged red blood cells. In rare cases, the baby may require an exchange transfusion, which involves removing the baby’s blood and replacing it with donor blood.
Treatment of HDNB
