QuestionSBA
QuestionChoice
This is incorrect because this is one of the investigations for hereditary spherocytosis, which presents in childhood with  jaundice, anaemia, and splenomegaly. There is typically a family history as the condition is inherited in an autosomal dominant pattern. It is a type of haemolytic anaemia, but this question stem ludes to warm autoimmune haemolytic anaemia caused by chronic lymphocytic leukaemia.
53199
c
Osmotic fragility test
QuestionChoice
Haptoglobin is a useful test when suspecting intravascular haemolysis. This patient has a past history of haemolytic anaemia but his haemaglobin at present is acceptable. There is no indication that he requires investigating for haemolysis at this stage.
53200
d
Haptoglobin
QuestionChoice
This is incorrect because bone marrow biopsies are rarely carried out as part of the initial work-up for CLL, since the diagnosis can be made on peripheral blood cytometry alone. It may be required further down the line, such as prior to initiating treatment, or to assess response to treatment.
53201
e
Bone marrow biopsy
QuestionChoice
This is incorrect because this is used to diagnose G6PD deficiency. This is an X-linked recessive disorder which usually presents with jaundice in neonates or during earlier years of life. It can be triggered by recent infections, fava beans, and medications such as primaquine, nitrafurantoin, and quinolones.  G6PD deficiency results in intravascular haemolysis, raised LDH, bilirubinuria, reticulocytosis, and bite cells/heinz bodies.
53198
b
Glucose-6-Phosphate-Dehydrogenase enzyme assay
QuestionChoice
Flow cytometry of peripheral blood is the first line investigation for chronic lymphocytic leukaemia, which this patient most likely has as indicated by the raised lymphocyte count and previous history of warm autoimmune haemolytic anaemia, which this patient has. CLL is often diagnosed incidentally since it remains asymptomatic for a prolonged period of time. Blood films show characteristic smudge/smear cells.
53197
a
Flow cytometry of peripheral blood
QuestionComment
why's the WCC really high if its lymphocytic leukaemia?
24790
User
subscriber
WBC Zebras
QuestionComment
Wcc includes lymphocytes and granulocytes e.g. neutrophils 
26127
User
subscriber
Kinase Sclerosis
QuestionComment
Reference ranges pleaaaassseee
28528
User
subscriber
Cystic Juice
QuestionComment
it doest ask for first line, I give up
61025
User
subscriber
Migraine Ketone
QuestionComment
Biopsy will be the best test for diagnosis, flow cytometry will be the next test
61482
User
subscriber
Abscess Flutter
QuestionComment
genuinely am NEVER going to be able to understand haematology for finals - send help and resources
62508
User
subscriber
Anti-D
Concept
Chapter
# Summary

Haemolytic anaemia is a condition characterised by the premature destruction of red blood cells (RBCs), resulting in a reduced RBC lifespan. It can be categorised into hereditary and acquired forms, and further divided into intravascular or extravascular and autoimmune or non-autoimmune subtypes. The epidemiology varies depending on the specific type. Diagnosing haemolytic anaemia requires a comprehensive set of investigations, including a complete blood count (FBC), split bilirubin, haptoglobin, lactate dehydrogenase (LDH), reticulocytosis, and blood film analysis. Additional tests may be needed, such as direct antiglobulin test (DAT), electrophoresis, and further blood film examination. Management involves addressing the underlying cause and may include blood transfusions, immunosuppressive therapy, or splenectomy. Complications can include severe anaemia, gallstones, and organ damage.

# Definition

Haemolytic anaemia is a condition characterised by the premature destruction of red blood cells (RBCs), leading to a decrease in their lifespan. This condition can be classified into hereditary and acquired forms, with further subdivisions based on the site of haemolysis, either intravascular or extravascular, and the underlying cause, autoimmune or non-autoimmune.


# Epidemiology

The prevalence and distribution of haemolytic anaemia vary significantly based on the specific subtype and its underlying causes:

- Sickle cell disease predominantly affects individuals of African descent, and is most prevalent in sub-Saharan Africa.
- Thalassemias: The distribution of thalassemias is linked to regions with a high prevalence of consanguineous marriages, notably in Mediterranean countries.
- The prevalence of autoimmune haemolytic anaemia varies, but it is often associated with autoimmune diseases like systemic lupus erythematosus. It can affect individuals of any age and ethnicity. 
- The incidence of intravascular haemolysis may be higher in conditions involving mechanical trauma, such as prosthetic heart valves or microangiopathic disorders. 
- Extravascular haemolysis is often observed in hereditary conditions like hereditary spherocytosis and can affect individuals worldwide.

# Classification

### Hereditary Haemolytic Anaemia
Includes conditions like sickle cell disease, thalassemias, and hereditary spherocytosis, often caused by genetic mutations affecting RBC structure or function.

### Acquired Haemolytic Anaemia

Can result from autoimmune disorders, infections (e.g., malaria), medication reactions, or mechanical trauma.
### Intravascular Haemolysis

Occurs within the bloodstream, leading to the release of free haemoglobin into the circulation and the excess of haemoglobin is dealt with in many ways: 

- Combination with haptoglobin
- Combination with albumin (**methaemalbuminaemia**)
- Loss in the urine (**haemoglobinuria**)
- Storage in tubular epithelial cells as **haemosiderin** 
- Shedding into the urine (haemosiderinuria)
	
Causes of intravascular haemolytic anaemia include:

- Intrinsic cellular injury (eg. G6PD deficiency)
- Intravascular complement-mediated lysis (some autoimmune haemolytic anaemias)
- Paroxysmal nocturnal haemoglobinuria and acute transfusion reactions
- Mechanical injury – microangiopathic haemolytic anaemia and cardiac valves
- Autoimmune haemolytic anaemia (AIHA)

### Extravascular Haemolysis

- Takes place outside the bloodstream, primarily in the spleen and liver, where RBCs are phagocytosed. It is not associated with dramatic release of free haemoglobin into the circulation. 
- Splenomegaly and hepatomegaly are typical.

Causes include:

- Abnormal red cells (e.g. sickle cell anaemia and hereditary spherocytosis)
- Normal cells having been marked by antibodies for splenic phagocytosis

### Autoimmune Haemolytic Anaemia

RBC destruction is triggered by autoantibodies that target the body's own RBCs.

Two major causes include:

1. Warm AIHA:
	-  An **IgG-mediated extravascular** haemolytic disease, in which the spleen tags cells for splenic phagocytosis. 
	-  Causes: **SLE,** idiopathic, lymphoproliferative neoplasms (eg. chronic lymphocytic leukaemia and lymphoma), drugs (methyldopa)
	-  Managed with prednisolone or immunosupression (e.g. AZT) and transfusions if severe 
2. Cold AIHA:	
	- **IgM-mediated** haemolytic disease, in which IgM fixes **complement** causing **direct intravascular haemolysis**. It includes cold agglutinin disease
	- The IgM agglutinates also cause the hands and feet to become blue in cold conditions (**acrocyanosis**)
	- Causes: post-infectious (usually after **Mycoplasma** or EBV), idiopathic, lymphoproliferative disorders
	- Treatment is mostly supportive, warmed blood is transfused if required and resistant cases may trial rituximab

### Non-Autoimmune Haemolytic Anaemia

Caused by factors other than autoantibodies, such as infections or mechanical stress:

- Microangiopathic haemolytic anaemia
- Paroxysmal nocturnal haemoglobinuria (PNH)
- Physical lysis of red cells (e.g. malaria, patients with mechanical heart valves)
- Haemolytic uraemic syndrome (HUS) – often caused by *E. coli* 0157:H7
- Infectious causes of disseminated intravascular coagulation (DIC) such as fulminant meningococcaemia

# Signs and Symptoms

**Haemolytic Anaemia - General:**

Haemolytic anaemia, regardless of its underlying cause, often presents with a constellation of symptoms related to the accelerated breakdown of red blood cells and the body's response to anaemia. Common signs and symptoms include:

- Fatigue 
- Pallor
- Jaundice - Haemolysis releases bilirubin into the bloodstream, causing yellowing of the skin and sclera 
- Splenomegaly - The spleen becomes enlarged as it works to remove and destroy the damaged red blood cells.
- Dark Urine
- Gallstones - Excess bilirubin can accumulate in the gallbladder, increasing the risk of gallstone formation.
- Leg Ulcers - In severe cases, reduced blood flow and oxygen supply can lead to painful leg ulcers.
- Shortness of Breath
- Heart Palpitations

**Specific Causes and Their Signs and Symptoms:**

- **Sickle Cell Disease:** Vaso-occlusive pain, acute chest syndrome, and strokes.
- **Thalassemias:** Profound anaemia, skeletal deformities, and organ enlargement.
- **Hereditary Spherocytosis:** Splenomegaly and fatigue due to haemolysis.
- **Autoimmune Haemolytic Anaemia:** Variable symptoms linked to haemolysis extent and underlying autoimmune conditions.
- **Infections (e.g., Malaria):** Fever, fatigue, and organ dysfunction.
- **Medication-Induced:** Variable symptoms, jaundice, and specific drug-related effects.

# Investigations

1. First Identify Haemolytic Anaemia:

	* Full Blood Count (FBC): Reveals low haemoglobin levels, elevated reticulocytes, and alterations in RBC indices.
	* Reticulocytosis: Increased levels of reticulocytes indicate active RBC production.
	* Blood Film Analysis: reveals characteristic changes in RBC morphology depending on underlying cause.
	* LFTs may reveal raised bilirubin
	* Raised LDH indicative of high cell turnover
	* Raised urinary urobillinogen

2. Identify the Cause:

	* Direct Antiglobulin Test (DAT): Detects the presence of autoantibodies on the RBC surface in autoimmune haemolytic anaemia.
	* Electrophoresis: Helps diagnose haemoglobinopathies like thalassemias and sickle cell disease.
	* Blood Film Examination: Further evaluates RBC morphology and inclusions.

# Management

Treatment aims to address the underlying cause and alleviate symptoms. General management principles include:

* **Supportive Care:** Blood transfusions to manage severe anaemia however this won't be curative as there will be ongoing haemolysis if the underlying cause is not managed.
* **Immunosuppressive Therapy:** In autoimmune haemolytic anaemia, medications like corticosteroids can reduce antibody production.
* **Splenectomy:** May be considered in certain cases, particularly hereditary spherocytosis.
* Specific management strategies depend on the type of haemolytic anaemia.


# References

[Patient.info - Haemolytic Anaemia](https://patient.info/doctor/haemolytic-anaemia)
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Haemolytic anaemia
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Haematology
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Haemolytic Uraemic Syndrome
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Haemolytic anaemia 6
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Quesmed Tutorial: Haematology
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Haemolytic anaemia
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Disseminated intravascular coagulation (DIC) 2
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Haemolytic anaemia
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Haemolytic disease of the newborn
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Haemolytic anaemia
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Quesmed Tutorial: Haemolytic Anaemia
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Haemolytic anaemia
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Complications of blood transfusions 2
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Haemolytic anaemia 7
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Haemolytic anaemia 5
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Haemolytic anaemia 2
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Haemolytic anaemia
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Quesmed Tutorial: Lymphoma
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Haemolytic anaemia 3
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Anaemia
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Clinical haematology
10700
Chronic lymphocytic leukemia (CLL) is a type of cancer characterized by the accumulation of abnormal B cells, and flow cytometry of peripheral blood is a key diagnostic tool that identifies these cells based on their specific surface markers, confirming the presence of CLL.
Presentation
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Fatigue
UkmlaTopic
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Clinical haematology
A 71-year-old male presents to the GP for a follow-up appointment after conducting blood tests for fatigue. He says this has been going on for the past 8 months. He has a past medical history of warm autoimmune haemolytic anaemia. His blood tests reveal the following: 


||||
|--------------|:-------:|---------------|
|Haemoglobin|95 g/L|(M) 130 - 170, (F) 115 - 155|
|White Cell Count|90x10<sup>9</sup>/L|3.0 - 10.0|
|Platelets|200x10<sup>9</sup>/L|150 - 400|
|Neutrophils|6.5x10<sup>9</sup>/L|2.0 - 7.5|
|Lymphocytes|70x10<sup>9</sup>/L|1.5 - 4.0|

His thyroid function, vitamin B12, and folate levels are normal.


Which of the following investigations is most likely to confirm the underlying diagnosis?
a