QuestionSBA
QuestionChoice
Acute hepatitis would present with grossly deranged liver enzymes and raised bilirubin. A raised bilirubin with anaemia and normal liver enzymes is more typical for haemolytic anaemia
33022
e
Hepatitis panel
QuestionChoice
This patient likely has acute haemolytic anaemia from glucose-6-phosphate dehydrogenase deficiency following ingestion of fava beans. Direct antiglobulin test (direct Coombs test) is used to determine whether the patient has immune-mediated haemolytic anaemia
33018
a
Direct antiglobulin test
QuestionChoice
G6PD enzyme assay is used to diagnose glucose-6-phosphate dehydrogenase deficiency. It is checked approximately 3 months following an episode of acute haemolysis, and so it would not be the next investigation
33021
d
Screen for red blood cell pyruvate kinase activity
QuestionChoice
This child is experiencing acute haemolytic anaemia, likely triggered ingestion of fava beans with underlying glucose-6-phosphate dehydrogenase deficiency. Bone marrow biopsy would not further aid in the diagnosis of the definitive cause of haemolytic anaemia
33020
c
Bone marrow biopsy
QuestionChoice
G6PD enzyme assay is used to diagnose glucose-6-phosphate dehydrogenase deficiency. It is checked approximately 3 months following an episode of acute haemolysis, and so it would not be the next investigation
33019
b
G6PD enzyme assay
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lmfao think everyone took an L here
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Fr...
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you are just doing the most now
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don't lie everyone read fava beans and ran to G6PD, we're all guilty here
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big pharma
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Gabriel Magalhaes
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# 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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Direct antiglobulin test
6604
Direct antiglobulin test (direct Coombs test) is used to determine whether the patient has immune-mediated haemolytic anaemia
A 6-year-old boy presents with his father to the emergency department with two days of progressive shortness of breath on exertion and new visible jaundice. He is normally fit and well and has reached all his developmental milestones. On questioning regarding the patient's diet, his father reports the child has been eating fava beans with every meal for the past week.


On examination, he appears well but is jaundiced. His chest is clear, and he has a smooth, palpable mass in the left upper quadrant; the abdomen is soft and non-tender.  

Blood tests:

|Serum|Result|Reference Range|
|-------------------|------|------------|
|Haemoglobin|68|130 - 170 mg/dL|
|White Cell Count|5.1|3.0 - 10.0 x 10⁹ /L|
|Platelets|162|150 - 400 x 10⁹/L|
|Reticulocytes|220|25 - 100 x 10⁹/L|
|Haptoglobin|19|50-220 mg/dL|
|Lactate Dehydrogenase|636|70 - 250 IU/L|
|Creatinine|95|60 - 120 µmol/L|
|Bilirubin|85|< 17 µmol/L|
|Alanine Aminotransferase|35|10 - 40 IU/L|
|Alkaline Phosphatase|89|25 - 115 IU/L|
|Gamma glutamyl transferase|21|9 - 40 U/L|


Peripheral blood film shows polychromasia and bite cells.


Which of the following is the next best investigation?
a