Haematology Flashcards
acute lymphoblastic leukaemia prevalence
most common cancer in paeds
2-5 yrs
males more
trisomy 21 increases
acute lymphoblastic leukaemia pathop
infection, genetic + environment
disruptions in regulation and proliferation of lymphoid precursor cells in bone marrow…excessive production of blast cells, drop in R.B.C, W.B.C and platelets
history ALL
anaemia - lethargy
thrombocytopenia - bruising
leukopenia - infection
bone pain
weight loss
malaise
headache
seizures
examination ALL
pale
excess bruising/bleeding
lymphadenopathy
hepatosplenomegaly
ddx ALL
immune thrombocytopenia, immune deficiency, reactive lymphodenopathy
investigations ALL
FBC - pancytopenia, anaemia, thrombocytopenia
blood film - blast cells
CXR - mediastinal mass
bone marrow aspirate
LP
risk scoring ALL
1-10 yrs - better prognosis
WCC>50 - poorer
females - better
blasts within CSF - poorer
morphology and cytology - effects prognosis
immediate management ALL
resus - high WCC requires hyperhydration to prevent hyperviscosity
if mediastinus mass - steroids
if infection - abx
definitive ALL
chemo - IV, PO, intrathecally
blood products and prophylactic anti-fungal
prognosis ALL
over 90% survive
follow up for 5 years
complications ALL
infertility
avascular necrosis
peripheral neuropathy
anxiety
2 types of acute leukaemia
acute lymphoblastic leukaemia (maj)
acute myeloid leukaemia
acute leukaemia pathophysiology
blood stem cell - can be lymphoid stem cell or myeloid stem cell
lymphoid - WBC
myeloid - RBC, WBC, platelets
genetic mutations in blood progenitor cells…causes developmental arrest…causing immature cells (myeloblasts) - less healthy cells…infection, anaemia, bleeding
childhood AML diagnosis
when bone marrow has 20% or more blasts
classification AML
FAB classification
MO-M7
morphological and histochemical characteristics
leukaemia cells spread
to CNS, skin and gyms
can form solid tumour called chloroma or granylocytic sarcoma
risk factors AML
Down’s syndrome
Li-Fraumeni Syndrome
Aplastic anaemia
Myelodysplasia
Affected sibling
3 main pathological processes acute leukaemia
bone marrow failure due to infiltration by blasts
blast infiltration of other tissues
systemic effects of cytokines released by leukaemic cells and of increased plasma viscosity (leucostasis)
acute leukaemia investigations
FBC- pancytopenia, neutropenic
blood film - blasts, atypical cells, leukoerythroblastic features
CXR - lymph gland enlargement
bone marrow aspirate - definitive diagnosis
LP
biopsy of chloroma
acute leukaemia bone marrow exam
aspirate - response to chemo and risk of relapse
light microscopy - classification
immunophenotyping - identify subtype
initial management acute leukaemia
IV chemo - induction (2 cycles 4 weeks apart) and post remission consolidation
long term managent acute leukaemia
post remission therapy - further chemo
and/or allogeneic haematopoeitic stem cell transplantation
bone marrow transplant - if chemo not work or relapses
complications acute leukaemia
neutropenic sepsis
myelosuppression
N+V
mucositis
hair loss
chemo agent and side effect AML
Doxorubicin Cardiotoxicitiy
Vincristine Peripheral neuropathy
Cyclophosphamide Reduced fertility
Cytarabine Hepatotoxicity
prognosis AML
5 year survival of 66%
if poor cytogenic features or response to therapy - <20% cured
haemophilia genetics
x linked recessive
more common in males
haemophilia A v B
A - factor VIII (more common)
B - factor IX
pathophysiology haemophilia
factor VIII is one of main clotting factors that contibutes to production of thrombin via intrinsic pathway. The intrinsic pathway is activated in response to endothelial collagen exposure…therefore lack of favot VIII…deficient in thrombin…results in insufficient production of fibrin for clot stabilisation
severity of haemophilia A
depends on plasma conc of factor VIII
if severe, may have no measurable factor in blood
risk factors haemophilia
male
family hx
hx haemophilia
prolonged, unexplained bleeding
recurrent episodes
spontaneous bleeding
joint pain, swelling, reduced ROM - haemarthrosis
examination haemophilia
active bleeding
pallor
bruising
haemarthrosis
haemophilia ddx
non accidental injury (social care)
von willebrand disease
vit K deficiency
ALL
investigations haemophilia
FBC - anaemia
coagulation screen - prolonged APTT, normal PT, factor will be low
CT head, joint aspiration - additional
management haemophilia
treating bleeds - in: one off infusion of factor
prophylaxis - regular IV infusion of factor
education
avoid contact sports
good dental hygeine
complications haemophilia
chronic arthopathy
development of factor VIII or IX inhibitors
transfusion related complications
lymphoma types
hodgkin and non hodgkin lymphoma
epidemiology lymphoma
over 10% of childhood cancers
on boys
older children
pathophysiology lymphoma
multifactorial
adults - obesity, smoking, alcohol
history lymphoma
EMV
immunosuppresed - transplant, previous cancers
weight loss, night sweats, fevers
examination lymphoma
non tender lymphadenopathy
if mediastinus - wheeze, difficulty breathing
SVC obstruction
ddx lymphoma
reactive lymphadenopathy
leukaemia
met malignancy
investigations lymphoma
FBC
UE - tumour lysis syndrome can cocur before tx begins
LDH - elevated
USS of area and nodes and biopsy
CXR - mediastinal nodes
full body CT
lymph node biopsy
risk scoring lymphoma
1 - single group of nodes or organ
2 - 2 or more groups of nodes or organs on same side of diaphragm
3 - in lymph nodes or organs on both sides
4 - diffuse involvement of nodes and organs such as liver and bones
B added to stage if B symptoms present - weight loss, night swats, fevers
immediate management haemophilia
airway compromise
high dose steroids
SVCO may require stenting of veins
hyperhydration in tumour lysis syndrome
definitive management lymphoma
chemo and possible radiotherapy, depending on stage
prognosis lymphoma
majority recover
hodgkin’s more favourable than non
complications lymphoma
tumour lysis syndrome, which is seen when rapid lysis of tumour cells causes release of large amounts of phosphorus, potassium and calcium leading to potential kidney damage. This is most likely to occur when chemotherapy is first commenced, but may occur beforehand
neurotropenia
alopecia
sub fertility
genetics sickle cell
a mutation in the gene encoding the haemoglobin subunit β, encoded by the beta globin gene. It is inherited in an autosomal recessive
epidemiology sickle cell
1 in 2,449 in the UK with a carrier risk of 1 in 89
marked variation by region
malarial hypothesis - survival advantage against malaria
increasing prevalence of HbS allele in high income countries
pathophysiology sickle cell
The HbS allele results from a single nucleic acid substitution from GAG to GTG in the beta globin gene. This causes glutamic acid to be substituted with valine. Individuals with one HbS allele (HbAS) are carriers while those who are homozygous for the HbS allele (HbSS) have sickle cell disease. This is the most common type of sickle cell disease, however it is also possible to have one HbS allele and a different faulty beta globin allele other than HbS (such as β-thalassaemia, written as HbSβ-thalassaemia
This makes it prone to sickling where it becomes rigid and distorts into crescent shape. in the deoxygenated state, HbS tetramers bind to each other and polymerise…vaso-occlusion and chronic haemolysis
risk factors sickle cell
black african, black caribbean - 1 in 200 affected, 1 in 10 carriers
next common - asian
lowest - white
sickle cells history
intermittent vaso-occlusive crises - severely painful, precipitated by hypoxia, infection, exercise, dehydration, acidosis
dactylitis
family history
examination sickle cell
Pallor, lethargy – due to anaemia
Jaundice – due to haemolysis
Fever
Tachycardia, tachypnoea
Digital redness, swelling and pain
ddx sickle cell
gout
acute abdomen
vaso occulsive crisis >7 days
consider osteomyelitis or avascular necrosis
investigations sickle cell
haemoglobin electrophoresis - HbA absence
high performance liquid chromatography
blood film - nucleated red cells, howell jolly bodies, sickle shaped
FBC and reticulocyte count
iron studies
X ray of long bones
CXR - acute chest syndrome
screening sickle cell
antenatal screening -
heel prick test
acute pain crisis sickle cell
analgesia
fluid
oxygen
abx if infection
prophylactic tx sickle cell
Hydroxycarbamide – reduces frequency of painful crises
Novel and experimental treatments – including L-glutamine, crizanlizumab and Voxelotor
Regular blood transfusions – targeted to maintain HbS <30%
complications sickle cell
increased susceptibility to infection - pneumococcal and salmonellavac
vaccinations sickle cell
seasonal influenza vaccines – annual
pneumococcal vaccines – every 5 years
hepatitis B vaccine – if receiving regular blood transfusions
other vaccines, such as meningococcal C or haemophilus influenza type B vaccine – may be advisable if they haven’t had them before
complications sickle cell
pulmonary hypertension
leg ulcers
priapism
chronic kidney disease
large-artery ischemic stroke
aplastic crisis
result from infection with parvovirus B19
prognosis sickle cell
median life expectancy is 58 years for HbSS and 66 years for HbSC and HbSbeta-thalassaemia
life expectancy increasing
infection or stroke - most common mortality
acute chest syndrome - adults
poor prognostic factors sickle cell
earlier first presentation
high frequency of vaso-occlusive crises
