Inherited Haematology Disorders Flashcards
Epidemiology of haemoglobinopathies
-Commonest inherited single gene conditions worldwide (7%) and now in the UK
-Ethnic distribution varies and reflects malaria risk
-Many variations and carrier states
Clinically important haemoglobinopathies
-α and β thalassemia
=Reduced rate of globin chain synthesis
-Sickle cell disorders
=Synthesis of structurally abnormal Hb
=Mainly HbS
=Also Hb C,D,O
Combination of genes in haemoglobinopathies
-4 α genes
=1 or 2 abnormal = carrier/trait
=3 or 4 abnormal = disease
-2 β genes
=1 abnormal = carrier/trait
=2 abnormal = disease
-Combinations can be important
=HbSC, HbS beta thalassemia
Investigations of haemoglobinopathies
-Family history and ancestry
-Full blood count
=Hb, RCC, MCV, MCH
-Blood film
-HPLC
=high performance liquid chromatography
=Measures Hb A, F, A2
=Detects abnormal haemoglobins (S, C etc)
Thalassemia traits in FBC
-Microcytic hypochromic RBC
=reduced MCV,MCH
-b thalassemia trait
=Mild anaemia, elevated HbA2, normal ferritin
-a thalassemia trait (1 or 2 gene deletion)
=mild anaemia, normal HPLC, normal ferritin
=Diagnosis of exclusion
Management of thalassemia
-Asymptomatic, no treatment required
-Avoid unnecessary iron supplementation
-Investigate anaemia
Describe b thalassemia major
-Severe hypochromic microcytic anaemia, ^retics
-2 β genes mutated/deleted – no HbA
-RBC breakdown/haemolysis (excess a chains)
=Severe anaemia by 3-6 months
=Jaundice/gallstones
-Haematopoietic overactivity
=Splenomegaly
=Bone changes
=Failure to thrive
B thalassemia major treatment
-Untreated => death in infancy/childhood
-Chronic transfusion
=Regular hospital visits
=Long term medication
=Alloantibody formation
-Iron overload – chelation
=Cardiac failure
=Liver failure
=Endocrine problems eg diabetes, growth
-Current life expectancy 40-50 years
-Consider bone marrow transplantation
What is the Sickle Cell Trait?
-HbAS
=Normal FBC parameters and film
=Abnormal Hb detected on HPLC
=Asymptomatic, no anaemia, no treatment required
What is Sickle Cell Disease (genes?)
-HbSS mainly
=also HbSC, HbSβthal (SO, SD)
=many African hospitals only test for HbS but carriership of AO, AC, AD also relevant for antenatal counselling
Pathophysiology of sickle cell
-Deoxygenated Hb S polymerisation->sickling
=Reversible->irreversible
=Rigid RBC -> RBC damage
=Increased by hypoxia, acidosis, cold, infection, low HbF
=Also NO deficiency, leucocytosis
-> chronic haemolysis – Hb 60-90g/l
-> acute vaso-occlusion
Acute complications of sicke cell
-Infection
=Life-threatening infection 2y to hyposplenism
=Prophylactic penicillin, vaccination
-Acute anaemia
=Splenic sequestration,
=Aplastic crises
=haemolytic crises
-Painful vaso-occlusive crises
-Chest crises
=life-threatening
-Stroke 10% by age 20 years
=Reduced by chronic transfusion in high risk patients
-Priaprism
=impotence, infertility
Management of painful vaso-occlusive crises
=Limb/back pain, dactylitis
=Simple analgesia used at home
=Aim for adequate pain control within 60mins of hospital arrival – often require opiates
=Ensure adequate hydration
=Avoid/treat hypoxia
=Examine/investigate/treat infection
=Watch for chest symptoms
The Kaplan-Meier Estimate
-Estimates probability of remaining stroke-free among patients receiving transfusion and patients on standard care
Chronic problems of sickle cell
-Chronic anaemia
-End-organ damage
=Renal failure, pulmonary hypertension, cerebrovascular disease
-Transfusion related
=Iron overload
=Alloantibody formation
