Anaemia and B12 deficiency Flashcards
What is Autoimmune Hemolytic Anemia (AIHA)?
A condition where the immune system attacks and destroys the body’s own red blood cells.
What are the two types of AIHA?
‘Warm’ and ‘cold’ AIHA, classified based on the temperature at which the antibodies best cause hemolysis.
What is the most common type of AIHA?
Warm AIHA.
At what temperature does haemolysis occur best in Warm AIHA?
At body temperature.
What type of antibody is typically involved in Warm AIHA?
IgG.
Where does haemolysis typically occur in Warm AIHA?
Extravascular sites, such as the spleen.
What are some general features of haemolytic anaemia?
Anaemia, reticulocytosis, low haptoglobin, raised lactate dehydrogenase (LDH), and indirect bilirubin.
What are specific diagnostic features of AIHA?
Positive direct antiglobulin test (Coombs’ test).
What type of antibody is typically involved in Cold AIHA?
IgM.
At what temperature does haemolysis occur best in Cold AIHA?
At 4 degrees Celsius.
How is hemolysis mediated in Cold AIHA?
By complement and is more commonly intravascular.
What are some symptoms associated with Cold AIHA?
Symptoms of Raynaud’s and acrocyanosis.
What are common first-line treatments for Warm AIHA?
Steroids, potentially combined with rituximab.
Why do patients with Cold AIHA respond less well to steroids?
Because the hemolysis is complement-mediated and primarily intravascular.
What is a common autoimmune disease associated with Warm AIHA?
Systemic lupus erythematosus.
What is the significance of the direct antiglobulin test in diagnosing AIHA?
It detects antibodies attached to red blood cells, confirming immune-mediated hemolysis.
What are the main categories of hereditary haemolytic anaemias?
Hereditary haemolytic anaemias can be subdivided into membrane, metabolism, or haemoglobin defects.
What are the types of membrane defects causing hereditary haemolytic anaemia?
Hereditary spherocytosis and elliptocytosis.
What is a common metabolic defect causing hereditary haemolytic anaemia?
G6PD deficiency.
What are haemoglobinopathies?
Disorders like sickle cell disease and thalassaemia that affect the structure or production of haemoglobin.
How can acquired haemolytic anaemias be classified?
Into immune and non-immune causes.
What are the immune causes of acquired haemolytic anaemia?
Autoimmune (warm/cold antibody type), alloimmune (transfusion reaction, haemolytic disease of the newborn), and drug-induced.
What is autoimmune haemolytic anaemia?
An autoimmune disorder where antibodies target own red blood cells, can be warm or cold type.
What are examples of alloimmune haemolytic anaemia?
Transfusion reactions and haemolytic disease of the newborn.
Which drugs can cause immune-mediated haemolytic anaemia?
Methyldopa and penicillin.
What characterizes non-immune causes of acquired haemolytic anaemia?
Characterized as Coombs-negative and includes mechanical, chemical, and infection-related causes.
What are examples of conditions that cause microangiopathic haemolytic anaemia (MAHA)?
Thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), disseminated intravascular coagulation (DIC), malignancy, and pre-eclampsia.
What role do prosthetic heart valves play in haemolytic anaemia?
Can cause mechanical destruction of red blood cells leading to haemolysis.
What is paroxysmal nocturnal haemoglobinuria?
A rare disorder where red blood cells break down at night.
How can infections lead to haemolytic anaemia?
Examples include malaria.
What drug-related cause is associated with non-immune haemolytic anaemia?
Dapsone is associated with causing non-immune haemolytic anaemia.
What is Zieve syndrome?
A rare clinical syndrome of Coombs-negative haemolysis, cholestatic jaundice, and transient hyperlipidaemia associated with heavy alcohol use.
How is Zieve syndrome typically resolved?
Typically resolves with abstinence from alcohol.
What happens in intravascular haemolysis?
Free haemoglobin is released, binds to haptoglobin, and when saturated, binds to albumin forming methaemalbumin.
What does haptoglobin bind to in intravascular haemolysis?
To free haemoglobin. Once saturated, haemoglobin binds to albumin.
What is methaemalbumin and how is it detected?
Methaemalbumin is a complex of haemoglobin and albumin formed when haptoglobin is saturated. It is detected by Schumm’s test.
What are the clinical manifestations of intravascular haemolysis?
Presence of free haemoglobin in the urine (haemoglobinuria) and haemosiderinuria.
What are some causes of intravascular haemolysis?
Mismatched blood transfusion, G6PD deficiency, red cell fragmentation (heart valves, TTP, DIC, HUS), paroxysmal nocturnal haemoglobinuria, cold autoimmune haemolytic anaemia.
How does G6PD deficiency typically cause haemolysis?
While it typically leads to intravascular haemolysis, there is also an element of extravascular haemolysis.
What is extravascular haemolysis?
Occurs when red cells are destroyed primarily in the spleen or liver rather than in the bloodstream.
What are some causes of extravascular haemolysis?
Haemoglobinopathies (sickle cell, thalassaemia), hereditary spherocytosis, haemolytic disease of the newborn, warm autoimmune haemolytic anaemia.
What is iron deficiency anaemia?
A condition characterized by a deficiency of iron, leading to a reduction in red blood cells or haemoglobin.
Who has the highest incidence of iron deficiency anaemia?
Preschool-age children.
What are the main causes of iron deficiency anaemia?
Excessive blood loss, inadequate dietary intake, poor intestinal absorption, increased iron requirements.
What is the most common cause of iron deficiency anaemia in pre-menopausal women?
Blood loss due to menorrhagia.
What dietary choices can lead to iron deficiency anaemia?
Vegans and vegetarians might develop it due to a lack of meat, although it can be offset by consuming dark green leafy vegetables.
What condition affects intestinal absorption leading to iron deficiency?
Coeliac disease.
Why do pregnant women have increased iron demands?
Due to the baby receiving iron from the mother and an increase in plasma volume which dilutes the blood.
What are common symptoms of iron deficiency anaemia?
Fatigue, shortness of breath on exertion, palpitations, pallor, koilonychia, hair loss, atrophic glossitis, post-cricoid webs, angular stomatitis.
Why is taking a patient history important in diagnosing iron deficiency anaemia?
To identify potential causes such as diet changes, medication, menstrual history, and signs of gastrointestinal issues.
What does a Full Blood Count (FBC) show in iron deficiency anaemia?
Demonstrates hypochromic microcytic anaemia.
How is serum ferritin used to assess iron deficiency?
It correlates with iron stores but can be elevated in inflammatory states, potentially masking iron deficiency.
What does a high Total Iron-Binding Capacity (TIBC) indicate?
Reflects low iron stores.
Why might endoscopy be recommended in cases of unexplained iron deficiency anaemia?
To rule out malignancy, especially in males and post-menopausal females with unexplained iron deficiency.
What is the typical treatment for iron deficiency anaemia?
Identifying and managing the underlying cause, and administering oral ferrous sulfate.
What are common side effects of oral ferrous sulfate?
Nausea, abdominal pain, constipation, diarrhoea.
Why should iron supplementation continue for 3 months after correcting the deficiency?
To replenish iron stores.
What are some iron-rich foods recommended for patients with iron deficiency anaemia?
Dark-green leafy vegetables, meat, iron-fortified bread.
What is the typical serum iron level in Iron Deficiency Anaemia?
Low, typically less than 8 µmol/L.
What is the typical serum iron level in Anaemia of Chronic Disease?
Low, typically less than 15 µmol/L.
How does the Total Iron-Binding Capacity (TIBC) differ in Iron Deficiency Anaemia compared to AOCD?
In Iron Deficiency Anaemia, TIBC is high; in AOCD, it is low.
What is the typical TIBC level in Iron Deficiency Anaemia?
High.
What is the typical TIBC level in Anaemia of Chronic Disease?
Low.
How does transferrin saturation compare between Iron Deficiency Anaemia and AOCD?
Both conditions have low transferrin saturation.
What is the typical ferritin level in Iron Deficiency Anaemia?
Low.
What is the typical ferritin level in Anaemia of Chronic Disease?
High.
What is macrocytic anaemia?
A type of anaemia where red blood cells are larger than normal.
What are the two main types of macrocytic anaemia based on bone marrow characteristics?
Megaloblastic and normoblastic, based on the appearance of the bone marrow.
What are megaloblastic causes of macrocytic anaemia?
Vitamin B12 deficiency, folate deficiency, secondary to drugs like methotrexate.
What vitamin deficiencies are megaloblastic causes of macrocytic anaemia?
Vitamin B12 and folate.
What is a common drug that can lead to megaloblastic macrocytic anaemia?
Methotrexate, which affects DNA synthesis.
What are normoblastic causes of macrocytic anaemia?
Alcohol, liver disease, hypothyroidism, pregnancy, reticulocytosis, myelodysplasia, cytotoxic drugs.
How does alcohol affect red blood cells to cause macrocytic anaemia?
Alcohol leads to direct toxic effects on bone marrow, impairing red blood cell production and causing larger red blood cells.
What systemic condition can lead to normoblastic macrocytic anaemia?
Hypothyroidism, which can affect metabolic processes and red blood cell production.
What is myelodysplasia and how is it related to macrocytic anaemia?
A disorder of bone marrow characterized by the abnormal development of blood cells, often leading to larger red blood cells.
What type of drugs are associated with normoblastic macrocytic anaemia?
Cytotoxic drugs used in chemotherapy that interfere with cell growth and division.
What is microcytic anaemia?
A type of anaemia where red blood cells are smaller than normal.
List some common causes of microcytic anaemia.
Iron-deficiency anaemia, thalassaemia, congenital sideroblastic anaemia, anaemia of chronic disease, lead poisoning.
Why is iron-deficiency anaemia classified as microcytic?
Due to a lack of iron, which is necessary for hemoglobin production; lower hemoglobin in each cell leads to smaller cells.
How does thalassaemia cause microcytic anaemia?
Results from a genetic defect in hemoglobin synthesis, leading to less hemoglobin and smaller red blood cells.
What is congenital sideroblastic anaemia?
A genetic disorder where red blood cells cannot properly incorporate iron into hemoglobin, resulting in ineffective iron usage and smaller red blood cells.
In what way can anaemia of chronic disease present as microcytic?
Although more commonly normocytic, it can appear as microcytic in certain phases or conditions.
What role does lead poisoning play in causing microcytic anaemia?
Lead inhibits several enzymes of the heme synthesis pathway, leading to decreased hemoglobin synthesis and smaller red blood cells.
What condition could a normal haemoglobin level with microcytosis indicate, aside from thalassaemia?
Polycythaemia rubra vera, which may cause secondary iron deficiency due to bleeding.
Why should new onset microcytic anaemia in elderly patients be urgently investigated?
To exclude underlying malignancy, as cancer can be a hidden cause of anaemia in the elderly.
What is the characteristic feature of beta-thalassaemia minor in terms of blood indices?
The microcytosis is often disproportionate to the mild anaemia.
What is normocytic anaemia?
A type of anaemia where red blood cells are normal in size but reduced in number.
What are common causes of normocytic anaemia?
Anaemia of chronic disease, chronic kidney disease, aplastic anaemia, haemolytic anaemia, acute blood loss.
How does anaemia of chronic disease cause normocytic anaemia?
Often related to low-grade inflammation which affects the body’s ability to use iron effectively, without altering red blood cell size.
What role does chronic kidney disease play in causing normocytic anaemia?
Due to reduced erythropoietin production, which is essential for red blood cell formation.
What is aplastic anaemia and how does it lead to normocytic anaemia?
A bone marrow failure syndrome resulting in reduced production of all types of blood cells, including normally-sized red blood cells.
Why does haemolytic anaemia often result in normocytic anaemia?
Due to the rapid destruction of red blood cells, the bone marrow responds by releasing new, typically normally-sized red blood cells.
What impact does acute blood loss have on red blood cell size?
Initially, red blood cells remain normal in size as the bone marrow responds to replace blood volume without specific changes to cell size.
What is pernicious anaemia?
An autoimmune disorder affecting the gastric mucosa that results in vitamin B12 deficiency, leading to megaloblastic anaemia and neuropathy.
What does ‘pernicious’ mean in the context of pernicious anaemia?
Causing harm, especially in a gradual or subtle way. Symptoms and signs are often subtle and diagnosis is often delayed.
What are some other causes of vitamin B12 deficiency besides pernicious anaemia?
Atrophic gastritis (often secondary to H. pylori infection), gastrectomy, malnutrition (e.g. alcoholism).
What is the pathophysiology of pernicious anaemia?
Autoantibodies target intrinsic factor and gastric parietal cells, blocking B12 absorption and reducing acid production, respectively.
Why is vitamin B12 important?
Essential for blood cell production and nerve myelination.
What are common risk factors for pernicious anaemia?
More common in females, middle to old age, those with blood group A, and associated with other autoimmune disorders like thyroid disease and type 1 diabetes.
What are typical features of anaemia seen in pernicious anaemia?
Lethargy, pallor, dyspnoea.
What neurological features are associated with pernicious anaemia?
Peripheral neuropathy, subacute combined degeneration of the spinal cord, and neuropsychiatric features like memory loss and confusion.
What are the key investigations used to diagnose pernicious anaemia?
Full blood count showing macrocytic anaemia, low vitamin B12 levels, antibodies to intrinsic factor and gastric parietal cells.
What are the treatment options for pernicious anaemia?
Vitamin B12 injections intramuscularly; frequency depends on presence of neurological symptoms. Oral vitamin B12 for maintenance is emerging.
What complication is associated with pernicious anaemia beyond haematological and neurological issues?
Increased risk of gastric cancer.
What is the primary function of Vitamin B12 in the body?
Vitamin B12 is essential for red blood cell development and maintenance of the nervous system.
How is Vitamin B12 absorbed in the body?
Vitamin B12 binds to intrinsic factor secreted by stomach parietal cells, then is absorbed in the terminal ileum; a small amount is absorbed passively without intrinsic factor.
What is the most common cause of Vitamin B12 deficiency?
Pernicious anaemia.
How can a vegan diet lead to Vitamin B12 deficiency?
Vegans avoid animal products, which are primary sources of Vitamin B12.
What role does metformin play in Vitamin B12 deficiency?
Metformin can occasionally reduce Vitamin B12 absorption.
What are the symptoms of Vitamin B12 deficiency?
Macrocytic anaemia, sore tongue and mouth, neurological and neuropsychiatric symptoms.
How does Vitamin B12 deficiency affect the nervous system?
Initial symptoms usually include problems with the dorsal column, like joint position and vibration sense, followed by distal paraesthesia.
What is the recommended management for Vitamin B12 deficiency without neurological symptoms?
Administer 1 mg of IM hydroxocobalamin 3 times each week for 2 weeks, then once every 3 months.
Why should B12 deficiency be treated before folic acid deficiency?
Treating B12 deficiency first prevents the potential worsening of neurological symptoms that can be precipitated by folic acid treatment.
