Path Haem 2 Flashcards
What proteins are most commonly mutated in hereditary spherocytosis?
Spectrin
or ankyrin
(they are RBC membrane proteins)
What is the inheritance pattern of hereditary spherocytosis?
Autosomal dominant (75% cases)
however 25% of cases are recessive or de novo
severity of hereditary spherocytosis
there is a range
mild (20-30%, often asymptomatic)
moderate (most common, usually presents in infancy or childhood)
severe (can even present in utero with hydrops fetalis)
What is the classic triad that hereditary spehrocytosis presents with?
anaemia
splenomegaly
jaundice (due to increased unconjugated bilirubin)
What additional risks are patients with hereditary spherocytosis at risk of?
- gallstone formation
- susceptibility to the effect of parvovirus B19 infection
- haemolytic / aplastic crises
- megaloblastic anaemia
What is the underlying pathophysiology in hereditary spherocytosis?
- Genetic mutation
→ defects in RBC membrane protein → sphere-shaped RBCs with decreased membrane stability
→ inability to change form while going through narrowed vessels
- Entrapment within splenic vasculature → splenomegaly
- Destruction via splenic macrophages → extravascular hemolysis
What type of gallstones do people with hereditary spehrocytosis get?
black pigment gallstones
(can lead to cholecystitis)
What findings can you see on blood smear in hereditary spherocytosis?
spherocytosis
potentially anisocytosis
How do you diagnose hereditary spherocytosis?
- spherocytes
- flow cytometry (EMA binding test)
- positive osmotic fragility test (increased osmotic fragility (lysis in hypotonic solutions))
- DAT -ve (Coombs) -> not immune mediated
Management of hereditary spherocytosis?
folic acid
splenectomy (sole definitive treatment)
phototherapy in neonates to prevent kericterus
blood transfusions may be required
What vaccines should you give before splenectomy?
strep pneumoniae
HiB
N. meningitidis
What are the functions of the spleen?
elimination of damaged erythrocytes from the blood stream
opsonisation and removal of encapsulated organisms from the bloodstream
What is asplenia?
absence of normal spleen function (functional asplenia) or of the spleen itself (anatomic asplenia)
you can also have congenital asplenia, but this is very rare (1 in 10 000)
typical blood smear + FBC findings in patients with asplenia
Howell-Jolly bodies
neutrophilia
thrombocytosis
Important considerations in the management of asplenia in patients
MedicAlert bracelet
prevent dog/tick bites
caution when travelling to malaria endemic areas
immunise against encapsulated organisms
treat with antibiotics early
What are the myeloproliferative disorders?
CML
ET (essential thrombocythaemia)
PV (polycythaemia vera)
PMF (primary myelofibrosis)
What can be seen on BM in myelofibrosis?
fibrosis
‘‘dry tap’’
What mutations are common in myelofibrosis?
JAK2 (60%) - Janus kinase
MPL mutation
CALR mutation
What is Budd-Chiari syndrome?
a rare condition resulting from hepatic vein obstruction that leads to hepatomegaly, ascites, and abdominal discomfort.
- It is most commonly due to a thrombotic occlusion secondary to a chronic myeloproliferative neoplasm (e.g., polycythemia vera), but may be caused by other conditions associated with hypercoagulable states.
What is the commonest and second most common inherited cause of exocrine pancreatic insufficiency in children?
- CF
- Schwachmann Diamond Syndrome
What is the classical inheritance pattern of G6PD deficiency?
X-linked recessive
What first line small molecule inhibitor is used in the treatment of chronic lymphocytic leukaemia?
Ibrutinib (tyrosine kinase inhibits)
What does CML do to the spleen and how?
Classically it causes massive splenomegaly due to splenic infiltration of myeloid cells.
What haematological changes are seen in pregnancy?
++ increased plasma volume
+ increased cell mass
- decreased Hb
+ increased MCV
decreased haemltocrit
decreased platelets
+ increased WCC
+ increased factors VII, VIIII, IX, X, XII
decreased Factor XI
decreased Protein S
route of administration of Anti-D in pregnancy
IM
but can also be given IV
When is routine antenatal prophylaxis of anti-D given?
28 and 34 weeks
What dose of anit-D is given during the routine antenatal timings and when are these?
250 IU
given IM at 28 and 34 weeks
