genetic conditions Flashcards
what does hydroycarbamide/ hydroxyurea do for sickle cell disease
increases the levels of HbF (two alpha two gamma)
what is haemoglobin normally made of
2 alpha globin chains (4 genes) and 2 beta globin chains (2 genes)
what are the consequences of thalassaemia
get haemolytic anaemia, get splenomegaly due to increased cell removal and EMH), get iron overload due to transfusions and get bone expansion
universal features of thalassaemia
microcytic anaemia, splenomegaly, jaundice, pallor
what are the three types of alpha thalassaemia
1) alpha thalassaemia trait
2) Haemoglobin H disease - 3 of the genes affected
3) Hydrops fatalis - all 4 of the alpha genes are defective, no alpha globin produced, not compatible with life
what are the types of beta thalassamia
causes increase in HbA2 (minor form of Hb in the adult which id made of two alpha two delta)
1) beta thalassaemia minor –> mild anaemia, just need monitoring
2) beta thalassaemia intermedia –> two defective genes or one defective and one deletion, get a more significant anaemia
3) beta thalassaemia major –> severe anaemia and failure to thrive. May have features like frontal bossing, enlarged maxilla and protruding teeth
MX for thalassaemia
- tranfusions
- folic acid
- screening in pregnancy
- splenectomy
- bone marrow transplant can be curative
what is the most common inherited thrombophilia
factor V leiden mutation
what is factor V Leiden mutation
activated protein C resistance (and protein C normally has a role in anticoagulation)
what is the consequence of factor V Leiden mutation
greater risk of VTE
what is the pathophysiology of an acute chest crisis in SCD
vasoocclusion of the pulmonary microvasculature which then causes infarction
symptoms of an acute chest crisis
sudden onset hypoxia, chest pain and see bilateral pulmonary infiltrates on Xray
Mx of an acute chest crisis
pain relief, o2, abx
what happens in a sequestration crisis in sickle cell disease
blood gets blocked in organs like the spleen due to sickling, but get a reticulocyte response as bone marrow is not affected (unlike in a aplastic crisis)
what is the pathophysiology of SCD
autosomal recessive point mutation of glu –> val on chromosome 11 which makes HbS and this is means it can sickle in stress (infection, cold, hypoxia, dehydration)
how might SCD present
anaemia, jaundice, in criss, recurrent infection due to hyposplenism, splenomegaly
key Ix for SCD
FBC (see high reticulocytes), blood film, Hb electrophoresis
-newborn screening
Mx of SCD
-avoid triggers of vasoocclusion like dehydration/ exhaustion
-abx prophylaxis and vaccinations
-may need transfusion
-hydroxycarbamide can be used to increase HbF
-in crisis can do exchange transfusion
complications of SCD
chronic pain, priapism, CKD, hyposplenism, avascular necrosis
what is the most common inherited clotting disorder
von willebrands disease (1%) of population
how does vWF normally present
commonly asymptomatic but can present with epistaxis, heavy menstrual bleeding
what is vWF normal role
mediates platelet aggregation to damaged endothelium and it has a role in the intrinsic (APTT) pathway where it is a carrier for factor VIII
what would bloods show for von willebrand disease
FBC normal, APTT normal or increased due to vWF being a carrier for FVIII, PT normal, fibrinogen normal
Mx of von willebrand disease
lifestyle - avoid things which increase the bleed risk, desmopressin
why can desmopressin be used to treat von willebrand disease
it increases the clotting factors in the blood
what kind of haemolysis do you get in hereditary spherocytosis
extravascular haemolysis as the spherocytes are removed from the circulation and then get destroyed by the spleen
what is the key diagnostic test for hereditary spherocytosis
MCHC (which is ELEVATED) due to the reduction in SA:vol
Mx of hereditary spherocytosis
same as for all the haemoglobinopathies
-tranfusions
-folic acid supplementation –> to keep up with the rate of production of the RBC
-splenectomy
characteristics of a warm haemolytic anaemia
CLL and autoimmune
-IgG and extravascular (extravascular means it happens in the spleen)
-Tx underlying condition or can treat with steroids or rituximab
characteristics of a cold haemolytic anaemia
IgM mediated, intravascular
-malignancy and infection!!
-present with raynauds like symptoms
-harder to treat
what is an example of an alloimmune haemolytic anaemia
ABO incompatibility reaction
what is the firstline investigation for a haemolytic anaemia
direct Coombs test (add Coombs reagent and look for agglutination)
what is the level of haptoglobin in a haemolytic anaemia
low as it mops up all the free Hb
complications of haemolytic anaemias
high output heart failure, pigmented gallstones and pruritus
what is it helpful to do if the cause of a haemolytic anaemia is unknown
a blood smear
what is haemolytic anaemia triggered by in a G6PDH deficiency
medications, fava beans or infections (which cause oxidative stress to cells and cells do not have any NADPH to then repair)
Investigations for G6PDH deficiency
G6PDH assay
what is Budd chairi syndrome
portal vein thrombosis
Ix for budd chairi syndrome
ultrasound with Doppler flow studies
how does Budd chairi syndrome present
abdo pain (sudden and severe), ascites and tender heptaomegely
what is acute intermittent porphyria
enzyme is defective in the biosynthesis of haem
-presents with abdominal and neuropsychological symptoms
-urine becomes red on standing
-high levels of porphobilinogen
-Triggered by hormones / pill
-Tx attacks with haem arginate
