Thalassemia Flashcards
what is thalassemia?
an autosomal RECESSIVE condition. genetic defect of the protein chain which makes up haemoglobin
(hb is made up of 2 alpha, 2 beta globin chains)
defect in alpha= alpha thalassemia
defect in beta= beta thalassemia
RBC are more fragile so break down easily. spleen acts as a sieve to filter and remove older blood cells. the spleen will collect all destroyed cells, resulting in splenomegaly.
bone marrow expands to produced extra RBC to compensate for chronic anaemia. susceptibility fractures, pronounced froehead and malar eminences (cheekbones)
signs and symptoms of thalassemia:
Microcytic anaemia (low mean corpuscular volume) Fatigue Pallor Jaundice Gallstones Splenomegaly Poor growth and development Pronounced forehead and malar eminences
investigation for thalassemia
Full blood count shows microcytic anaemia.
Haemoglobin electrophoresis is used to diagnose globin abnormalities.
DNA testing can be used to look for the genetic abnormality
*offered to all pregnant women
iron overload in thalassemia
occurs as a result of faulty creation of RBC, recurrent transfusion or increased absorption of iron
symptoms of iron overload in thalassemia: Fatigue Liver cirrhosis Infertility and impotence Heart failure Arthritis Diabetes Osteoporosis and joint pain
monitor serum ferritin levels to check for iron overload. mx: limit transfusion and iron chelatoin.
alpha-thalassemia
defect in the alpha globin chain
chromosome 16
mx: Monitoring the full blood count Monitoring for complications Blood transfusions Splenectomy may be performed Bone marrow transplant can be curative
beta thalassemia
defect in beta-globin chain
chromosome 11
gene defects:-
- abnormal copies that retain function
- deletion of genes where there is no function in the btta globin protein at all
Thalassaemia minor
Thalassaemia intermedia
Thalassaemia major
thalassemia:
minor
intermedia
major
minor: abnormally functioning beta-globin gene. one abnormal and one normal gene. microcytic anaemia. monitor but no active tx
intermedia: two abnormal copies of the beta-globin gene. two defective genes / one defective gene / one deletion gene.
significant microcytic anaemia, monitor and occasional blood transfusion may require iron chelation to prevent iron overload
major: homozygous for the deletion gene. no functioning beta-globin genes at all. most severe form. severe anaemia/failure to thrive in early childhood:
Severe microcytic anaemia
Splenomegaly
Bone deformities
regular monitor, regular transfusion, iron chelation and splenectomy. bone marrow transplant is potentially curative.
what is sickle cell anaemia
a genetic condition that causes sickle (crescent) shaped RBC. blood cells are more fragile and easily destroyed leading to haemolytic anaemia
polymer forms of multiple beta globins
pathophysiology of sickle cell anaemia
Hb is the protein in RBC which transports O2
fetal haemoglobin (HbF) is usually replaced by adult haemoglobin (HbA) at 6 weeks. patients with sickle cell have an abnormal variant called haemoglobin S (HbS) (sickle shape)
autosomal recessive
the abnormal gene for beta-globin on chromosome 11
1 copy of gene= sickle trait, usually asymptomatic
2 abnormal copies= sickle cell dsiease
sickle cell and malaria
common in patients traditionally affected by malaia
having one copy reduces the severity of malaria (selective advantage)
diagnosis of sickle cell anaemia
offered test during pregnancy if the risk of being a carrier
sickle cell is tested in the newborn screening heel prick test at 5 days of age.
complications of sickle cell
Anaemia Increased risk of infection Stroke Avascular necrosis in large joints such as the hip Pulmonary hypertension Painful and persistent penile erection (priapism) Chronic kidney disease Sickle cell crises Acute chest syndrome
sickle cell general management
Avoid dehydration and other triggers of crises
Ensure vaccines are up to date
Antibiotic prophylaxis to protect against infection with penicillin V (phenoxymethypenicillin)
urine culture and blood culture
pain 20-30mg of morphine
CXR
ICU and haematology- intubation and ventilation.
Hydroxycarbamide (also used in myeloproliferative disorders) can be used to stimulate production of fetal haemoglobin (HbF). Fetal haemoglobin does not lead to sickling of red blood cells. This has a protective effect against sickle cell crises and acute chest syndrome.
hydroxyurea
P selectin inhibitors- cirzanlizumab
beta-globin chain polymerisation - voxelotor.
(exchange transufsion) Blood transfusion for severe anaemia
Bone marrow transplant can be curative
all sickle patients should be on the following:
- folic acid
- penicillin
- hydroxycabamide
sickle cell crises
the spectrum of acute crises related to the condition. can be mild/life-threatening. can be spontaneous or triggered by stressors= infection, dehydration, cold, significant life events.
manage supportively:
Have a low threshold for admission to hospital
Treat any infection
Keep warm
Keep well hydrated (IV fluids may be required)
Simple analgesia such as paracetamol and ibuprofen
Penile aspiration in priapism
avoid NAIDS if renal impairment
vaso occlusive crisis (painful crisis)
the sickle-shaped blood cells clog the capillaries which cause distal ischaemia.
associated with dehydration and haematocrit.
pain, fever, priapism (blood trapped in the penis causing a painful and persistent erection) aspirate blood from the penis.
