T7-L4: Haemaglobinopathies Flashcards
What are physiological haematological changes during pregnancy?
- Plasma volume expands in pregnancy by 50%
- Red cell mass expands by 25%
- Haemodilution occurs as a result - maximally at 32 weeks
- MCV (mean cell volume) increases so macrocytosis is common
- Also tend to see a neutrophillia (left shift)
- Thrombocytopenia
- Pregnancy is a prothrombotic state
CDC define anaemia as HB < 110 g/L in the first and 3rd trimester and <105 in the second trimester.
Anaemia must be investigated. Iron deficiency is the most common cause. Pregnancy increases requirements for iron and usually results in considerable metabolism of iron stores.
What is neutrophilic left shift in pregnancy?
Left shift describes when immature neutrophils are released from the bone marrow due to an outpouring of cells. However, this neutrophilia is not usually associated with infection or inflammation.
What in the clinical presentation of sickle cell trait?
Blood count: Normal
Hb Electrophoresis: Hb-S 45% and Hb-A 55%
Clinical presentation: Usually a benign processes. No issues except in extreme hypoxia/dehydration. A higher frequency of haematuria is seen.
Why does sickle cell anaemia not present immediately at birth?
Sickle cell does not present immediately at birth due to the presence of Hb-F. Some people have persistence of Hb-F into adult life reducing the severity.
What factors contribute to sickle cell vasculopathy?
- Sickle cell can also be seen as a pro-inflammatory state. There is elevation in inflammatory cytokines, leucocytes, CRP etc. This upregulates inflammatory adhesion molecules. These interaction with sickle red cells causing damage to the endothelium. Platelets and leucocytes can interact with the endothelium.
- Also with intravascular haemolysis there is release of free haemoglobin. This leads to nitric oxide depletion leading to a prothrombotic processes. These both contribute to sickle cell vasculopathy.
What is the presentation of Sickle Cell disease?
Blood count: Anaemia
Blood film shows sickle cells
Hb Electrophoresis: Hb-S >95% and Hb-A - 0%
Found in Afro Caribbean population and 1 in 60 in West Africans.
Presents in infancy around 3-6 months as the Hb-F leaves circulation - this leads to jaundice, painful swelling in the hands and feet (dactylitis due to sickling in the vessels around the digits), enlarged spleen, repeated infarction and damage to the spleen damages it leading to hyposplenism (it can be so small its undetectable in an adult).
Why is there an increased risk of infection in patients with sickle cell anaemia?
Due to hypo-splenism. Sickle cells can block the blood vessels leading out of the spleen. When this happens, blood stays in the spleen instead of flowing through it. This causes the spleen to get bigger, and the blood counts to fall.
It normally function to remove encapsulated bacteria so there is a greater risk of pneumococcal sepsis and so prophylaxis bacteria are used. In sickle infants pneumococcal sepsis or splenic sequestration (red cells rapidly enlarge the spleen causing acute anaemia) are big causes of mortality.
What are complications of sickle cell anaemia?
- Vaso-occulsive crisis
- Septiocaemia
- Aplastic crisis
- Sequestration crisis
- Stroke
Chronically complications include:
- Hyposplenism
- Renal disease
- Avascualr necrosis
- Leg ulcers, osteomyelitis, gall stones, retinopathy, cardiac and respiratory
How does Hydroxycarbamide work?
Increases Hb F (time to delay to polymerisation, reduced adhesion to endothelium and enhances NO).
What is Alpha Thalassaemia?
- If they inherit an alpha mutation (thereby they cannot produce the globin at all, this impacts on the fetus. Therefore only F chains are produced. This can be detects on electrophoresis. This is incompatible with life - known as Hb Barts - leads to hydrops fetalis.
- Those with HbH disease survive fetal life. In this case there is reduced alpha haemoglobin. The condition usually causes a mild to moderate haemolytic anaemia, which may or may not require medical intervention. Cases can be severe – usually during an acute illness or increased metabolic exacerbation, such as during pregnancy.
- Both Hb A and F have α chains and so fetal hemoglobin production is defective
What is Hb-H disease?
Hb H disease - coinherited an alpha - defect form one parent and alpha+ from another. This results in a thalassemia intermediate phenotype. A transfusion is not needed in the first few months. They have a hemoglobin of 70-80 Hb. The spleen will be enlarged with a hemolysis aggravating other issues.
Hemoglobin H (HbH) disease is a moderate to severe form of alpha-thalassemia characterized by pronounced microcytic hypochromic hemolytic anemia.
What is Thalassaemia intermedia?
Beta- thalassemia intermedia, the milder form of the disorder, reduces the body’s ability to produce “adult” hemoglobin and causes anemia. The characteristic finding of beta thalassemia is anemia, which is caused because red blood cells are abnormally small (microcytic), are not produced at the normal amounts, and do not contain enough functional hemoglobin.
It presents with:
- Pulmonary HTN
- Extra medullary haematopoesis
- Bone changes and osteoporosis
- Endocrine and fertility issues
- Leg ulcers
What is the pathology of beta-thalassaemia?
- Alpha chain excess - leads to ineffective erythropoiesis and shortened red cell lifespan - this leads to anaemia.
- Increased marrow activity - leads to Skeletal deformity, stunted growth; Increased iron absorption (exacerbated by blood transfusion) and organ damage and protein malnutrition.
- Enlarged and overactive spleen - causes pooling of red blood cells (increased anaemia) and increased perfusion requirement.
What are the consequences of severe iron overload?
This can occur as a result of blood transfusion. consequences include:
- Gonads/hypothalmus - failure of puberty, growth failure
- Pancreas - Diabetes
- Heart - Dilated cardiomyopathy and heart failure
- Liver - Cirrhosis
