Haematology 3 Flashcards
Who do B-thalassaemias affect?
Indian subcontinent, mediterranean and middle east
What are the 2 main types of B-thalassaemia?
o β-Thalassaemia major: this is the most severe form of the disease, HbA (α2β2) cannot be
produced because of the abnormal β-globin gene
o β-Thalassaemia intermedia: this form of the disease is milder and of variable severity, the β- globin mutations allow a small amount of HbA and/or a large amount of HbF to be produced
What are the clinical features of B-thalassaemia?
Severe anaemia- transfusion dependent from 3-6 months of age and jaundice FTT/growth failure • Extramedullary haemopoiesis- can lead to hepatosplenomegaly and bone marrow transfusions Pallor Jaundice Bossing of the skull Maxillary overgrowth Splenomegaly Hepatomegaly
What is the management for B-thalassaemia?
Is fatal without regular blood transfusions (lifelong, monthly)
Maintain Hb over 10g/dl
Patients are treated with iron chelation with subcutaneous desferrioxamine, or with an oral iron chelator drug, such as deferasirox, starting from 2 to 3 years of age (chronic iron overload)
What are the features of chronic iron overload?
Cardiac failure Liver cirrhosis Diabetes Infertility Growth failure
What are the complications of multiple blood transfusions?
o Iron deposition- the most important (all patients)
Heart- cardiomyopathy
Liver- cirrhosis
Pancreas- diabetes
Pituitary gland- delayed growth and sexual maturation
Skin- hyperpigmentation
o Antibody formation- 10% of children
Allo-antibodies to transfused red cells in the patient make finding compatible blood very difficult
o Infection – now uncommon, <10% of children
Hepatitis A, B, C
HIV
Malaria
Prions- e.g. new variant CJD
o Venous access- common problem
Often traumatic in young children
Central venous access device (e.g. Portacath) may be required; these predispose to infection.
What is the alternative treatment for B-thalassaemia major?
Bone marrow transplantation
generally reserved for children with an HLA-identical sibling as there is then a 90– 95% chance of success, but a 5% chance of transplant-related mortality.
How is B-thalassaemia diagnosed prenatally?
- For parents who are both heterozygous for β-thalassaemia- there is a 1 in 4 risk of having an affected child.
- Prenatal diagnosis of β-thalassaemia should be offered together with genetic counselling to help parents to make informed decisions about whether or not to continue the pregnancy eg. DNA analysis of a chorionic villus sample
What is B-thalassaemia trait?
Heterozygotes are usually asymptomatic- but the red cells are hypochromic and microcytic
Anaemia is mild and absent
most important diagnostic feature is a raised HbA2, usually about 5%, and in about half there is a mild elevation of HbF level of 1–3%.
can be distinguished by measuring serum ferritin, which is low in iron deficiency but not β- thalassaemia trait
• To avoid unnecessary iron therapy, serum ferritin levels should be measured in patients with mild anaemia and microcytosis prior to starting iron supplements.
What is a-thalassaemia major?
Deletion of all four α-globin genes, so no HbA (α2β2) can be produced, it occurs mainly in families of South-east Asian origin and presents in mid-trimester with fetal hydrops (oedema and ascites) from fetal anaemia- always fatal in utero or within hours of delivery
Only long-term survivors have received monthly intrauterine transfusions until delivery followed by lifelong monthly transfusions after birth
diagnosis is made by Hb electrophoresis or Hb HPLC (high-performance liquid chromatography), which shows only Hb Barts.
What are the other a-thalassaemias?
3 a-globin genes deleted (HbH disease)- mild-moderate anaemia, sometimes transfusion dependent
A-thalassaemia trait- 1 or 2 a-globin genes. Anaemia is mild or absent, red cells may be hypo chromic or microcytic, may cause confusion with IDA
How is the severity of thrombocytopenia measured?
o Severe thrombocytopenia (platelets <20 × 109/L)- risk of spontaneous bleeding
o Moderate thrombocytopenia (platelets 20–50 × 109/L) at risk of excess bleeding during operations or trauma but low risk of spontaneous bleeding
o Mild thrombocytopenia (platelets 50–150 × 109/L), low risk of bleeding unless there is a major operation or severe trauma.
What does thrombocytopenia result in?
Bruising Petechiae Purpura Mucosal bleeding E.g epistaxis, bleeding from gums Major haemorrhage (GI) Haematuria Intracranial bleeding
What are the causes of thrombocytopenia?
o Increased platelet destruction or consumption
Immune: ITP, SLE, alloimmune neonatal thrombocytopenia
Non-immune: haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura, DIC, congenital heart disease, giant haemangiomas, hypersplenism
o Impaired platelet production
Congenital: Fanconi anaemia, Wiskott-Aldrich syndrome, Bernard-Soulier syndrome
Acquired: aplastic anaemia, marrow infiltration (leukaemia), drug-induced
o Platelet dysfunction
Congenital: rare disorders – eg. Glanzmann thromboasthenia
Acquired: uraemia, cardiopulmonary bypass
o Vascular disorders
Congenital: Ehlers-Danlos, Marfan syndrome
Acquired: meningococcal, vasculitis (SLE, Henoch-Schonlein purpura), scurvy
What is immune thrombocytopenia?
Commonest cause in childhood
Caused by destruction of circulating platelets by anti-platelet IgG autoantibodies- the reduced platelet count may be accompanied by a compensatory increase of megakaryocytes in the bone marrow
2-10yrs, onset after 1-2 weeks of a viral infection
