1- haemoglobinopathies & sickle cell

Question 1

what makes up haemoglobin? structure

Answer 1

2 alpha globin and 2 beta globin chains with 1 haem group attached to each globin chain

*there’s a few different structures but this is most common

Question 2

what age are adult haemoglobin started being made?

Answer 2

adult haemoglobin by 6-12 months

Question 3

what are haemoglobinopathies? what are the 2 main groups?

Answer 3

group of hereditary conditions affecting globin production due to mutations and deletions (tend to be autosomal recessive)

2 main groups
1. thalassaemias
2. haemoglobin variants

Question 4

what are thalassaemias? what happens if severe?

Answer 4

hereditary condition where normal globin chain made but not enough of them made so impaired Hb production

• get subtypes of alpha thalassaemia and beta thalassaemia
• if severe, unbalanced accumulation of globin chains mean toxic to cell and bone marrow works overtime but not successfully so chronic haemolysis of defect RBCs

Question 5

what are the different degrees of alpha thalassaemias? (loads of info!! can split up later if want)

Answer 5

alpha thalassaemias = delete 1 or more of the 4 alpha genes (more deletions = more severe)

1. alpha thalassaemia trait = missing 1 or 2 of the 4, asymptomatic, completely well, very common, no treatment but can cause confusion as people mistaken as iron deficient (check ferritin to rule out iron deficiency)
2. HbH disease = only 1 of 4 genes working, other 3 deleted, very low MCV, rare, compensated by excess beta chains making special haemoglobin. jaundice & splenomegaly →may need transfusion
3. Hb Barts hydrops fetalis = no functional alpha genes, incompatible with life (very serious). can make no foetal or alpha haemoglobin, without intrauterine transfusion, death before delivery. very rare. almost all die in utero

Question 6

what are degrees of beta thalassaemia? (another big info card)

Answer 6

beta thalassaemia = when mutations in either or both of the 2 beta genes

1. beta thalassaemia trait = very common carrier state, asymptomatic, don’t mistake for iron deficiency, diagnose by raised HbA2
2. beta thalassaemia intermediate = moderate severity requiring occasional transfusion
3. beta thalassaemia major = both beta chains have severe mutation, need lifelong transfusion as can’t make adult. over 1st year of life will present (won’t present at birth). baby fail to thrive, pale, hepatosplenomegaly, skeletal changes. if don’t get picked up make big problems like cord compression from extramedullary haematopoiesis

Question 7

what is management of beta thalassaemia major?

Answer 7

regular transfusion to maintain Hb at about 100 (enough to keep them well)

= can get iron overload from transfusion which can be lethal if don’t treat

Question 8

what are consequences of iron overload? and treatment?

Answer 8

consequences = endocrine dysfunction, accumulation of iron in liver & heart leading to cirrhosis, cardiomyopathy, arrhythmias etc

management = iron chelators drugs (cholators bind to iron in body making complexes that get excreted)

Question 9

what are sickle cell disorders?

Answer 9

= point mutation swapping amino acid in beta globulin altering structure of haemoglobin making HbS which does work under right physiological conditions but can stick together, polymerises, distorting and damaging RBC

Question 10

what is sickle cell trait?

Answer 10

not a disease, very common, it’s when you’re an asymptomatic carrier. you inherit 1 normal gene and 1 HbS so not enough HbS to cause problem

Question 11

what is sickle cell anaemia?

Answer 11

inherited HbS from both parents, faulty genes can’t make normal Hb causes loads of problems = sickle cell crisis

Question 12

what is sickle cell crisis?

Answer 12

• when episodes of tissue infarction due to vascular occlusion (from faulty HbS) - can cause severe pain & symptoms depending on site
• also get chronic haemolysis since RBC lifespan shorter, means spleen & liver get damaged. hyposplenism = since chunks of spleen dying since repeated infarcts

Question 13

what are some precipitants of sickle crisis (like triggers)?

Answer 13

• hypoxia
• dehydration
• infection
• cold exposure
• stress/fatigue

Question 14

what is treatment of sickle cell crisis?

Answer 14

• opiate analgesic (high dose til pain settles)
• hydration & rest
• oxygen & antibiotics if need
• red cell exchange transfusion in severe crisis (lung, chest, brain etc) to reduce proportion HbS in blood

Question 15

what is long term care of sickling disorders?

Answer 15

= particularly in babies biggest cause of death is infection so prophylactic penicillin very important. vaccines also very important.

• also folic acid supplements as increased RBC turnover needs higher demand of folate (good for all people with haemolysis)
• hydroxycarbamide = reduces severity
• regular transfusion to prevent stroke in selected cases

Question 16

what is done for haemoglobinopathy diagnosis?

Answer 16

1. full blood count & blood film
2. high performance liquid chromatography or electrophoresis to count Hb
   
   • also identifies abnormal Hb e.g. HbS

screening for haemoglobinopathies

• antenatal screening
• family origin questionnaire