Haematology Flashcards
types of ALL
- B cell (80%)
- T cell
risk factors for ALL
trisomy 21
chemotherapy
immunodeficiency syndromes e.g. wiskott aldrich syndrome
ionising radiation
chromosomal breakage e.g. fanconi anaemia , ataxia telangiectasia
presentation of ALL
bleeding/ bruising/ petechiae - thrombocytopenia
weight loss
SOB, pallor, malaise - anaemia
increased infections - neutropenia
bone and joint pain
lymphadenopathy
splenomegaly/ hepatomegaly
investigations for ALL
- blood film* -> BLAST CELLS (single large nucleus, high nuclear to cytoplasmic ratio)
- lumbar puncture * -> send for cytogenetics and minimal residual disease
- bone marrow aspiration ** -> >20% blast cells, high nuclear to cytoplasmic ratio
- CXR - mediastinal mass - important initial test before transfer
- FBC
- cytogenetics for associated translocations e.g. t (12,21)
factors indicating worse prognosis in ALL
boys
high WCC >50
minimal residual disease +ve
t(9,22), 11q23
hypodiploidy
< 2 y/o and >9 y/o
CNS disease
afro-caribbean
management of ALL
- initial IVF to prevent TLS
- chemotherapy - induction + consolidation (intrathecal methotrexate) + maintenance (oral dex)
cell cycle components
- G 1 - gap phase -> synthesis of components for DNA, under influenxe p53 gene, acts as checkpoints
- S - DNA synthesis
- G2 - 2nd gap phase
- M - mitotic stage
- G 0 - resting phase (cells most resistant to chemo drugs)
side effects of vincristine
neuropathy
constipation
jaw pain
foot drop
epidemiology of AML
highest rates < 1 y/o
15% of leukaemias
investigations for AML
- bone marrow aspiration and biopsy - immature myeloid lineage cells
- blood film - blast cells and auer rods
mutation in CML
philadelphia chromosome - translocation with chromosome 9 + 22 and BCR transcription factor with AB1 kinase
red flags for lymphadenopathy
supraclavicular lymph node
painless , enlarging, firm lymph node
B symptoms - night sweats, weight loss, fever
LN > 2cm
unexplained bruising
hepatosplenomegaly
what is tumour lysis syndrome
release of intracellular metabolites into blood after rapid lysis of malignant cells
crystallisation of uric acid or phosphate causes acute renal failure
blood tests for tumour lysis syndrome
hyperkalaemia
hyperphosphataemia
increased uric acid
increased urea
metabolic acidosis
hypocalcaemia
management of tumour lysis syndrome
- IV fluids !!!!!
- rasburicase - increases solubility of uric acid so it is secreted as allantoin
- allopurinolol - inhibits xanthine oxidase so blocks uric acid production
- may require haemofiltration if severe
presentation of superior vena cava obstruction
dyspnoea
distended chest and neck veins
horaseness of voice
facial swelling
risk factors for hodgkins lymphoma
SLE
rheumatoid arthritis
EBV
immunodeficiency disorders
types of hodgkins lymphoma
- nodular sclerosing *
- mixed cellularity
- lymphocyte rich
- lymphocyte depleted
presentation of hodgkins lymphoma
slow growing painless lymph node enlargement - cervical, supraclavicular, axilla
alcohol induced nodal pain
B symptoms
splenomegaly
local compression e.g. SVC obstruction, airway obstruction
diagnosis of hodgkins lymphoma
lymph node biopsy ** -> reed sternberg cells (multinucleated, giant lymphocyte cell)
CT - ann arbor classification
CXR - widened mediastinum
epidemiology of non hodgkins
5 x more common than hodgkins
originates from B or T lymphocytes
classification of non hodgkins lymphoma
- IMMATURE FORMS - T or B cell
- MATURE FORMS - Burkitts B cell (de novo mutation)
- LARGE CELL LYMPHOMAS - diffuse B cell, peripehral T cell, anaplastic large cell
presentation of non hodgkins lymphoma
painless slowly growing progressive peripheral lymphadenopathy
primary extranodal involvement and systemic symptoms e.g. B symptoms
burkitts can present with large abdo mass
diagnosis of non hodgkins lymphoma
- flow cytometry - identify absence of protein markers and differentiate between T and B cell types
- CXR
- lymph node excision
describe medulloblastoma
embryonic tumour of neuroendothelial tissue (usually in POSTERIOR FOSSA and CEREBELLUM -> cause hydrocephalus)
Presentation of medulloblastoma
headache - early morning
nausea and vomiting
ataxia, unsteady
papilloedema
obstructive hydrocephalus
investigations for brain tumour
MRI head and spine
Increased nuclear- cytoplasmic ratio = worse prognosis (feature of anaplastic cells)
management of medulloblastoma
chemo - cisplatin and vincristine
surgery
radiotherapy
most common brain tumour
astrocytoma / glioma - arises from glial precursor cells, AFFECTS MACROGLIA
- low grade - less agressive
- high grade - undifferentiated highly malignant, worse prognosis
how does a craniopharyngioma present
- headache
- visual disturbance
- hormonal imbalance e.g. diabetes insipidus
most common solid tumour in children
NEUROBLASTOMA
develops from neuronal ganglia of the peripheral sympathetic system
embryonal cancer and develops from VENTROLATERAL NEURAL CREST CELLS which migrate away from neural tube
60% arise from abdominal paraspinal ganglia + 30% arise from adrenal medulla
presentation of neuroblastoma
non tender mass across the midline
hypertension
abdominal pain, change in bowels
weight loss
Horners syndrome (if superior cervical gnaglion affected)
sweating
diagnostic tests for neuroblastoma
URINE CATECHOLAEMINES - Homovanillic acid and VMA elevated
CT abdo pelvis + biopsy ***
can resolve spontaneously
poorer prognosis factor in neuroblastoma
MYCN n-myc gene - proto oncogene -> requires more intensive therapy
risk factors for wilms tumour
family history
genetic defects e.g. WT1 gene
Beckwith wiedemann syndrome
trisomy 18
BRAC2 mutation in fanconi anaemia
Denys drash syndrome (ambiguous genitalia, b/l)
WAGR
presentation of wilms tumour
painless haematuria
abdominal mass - asymptomatic
hypertension
weight loss
diagnostic test for wilms tumour
CT abdomen or MRI
DIFFUSE ANAPLASIA = unfavourable diagnosis and needs more aggressive treatment
management of wilms tumour
radiotherapy + chemotherapy + surgical resection via radical nephrectomy with LN sampling
where does osteosarcomas affecr
metaphyseal region of long bones - usually distal femur or proximal fibula/ tibia
x ray changes in osteosarcoma
osteolytic cortical lesions
cortical erosion
cortical thickening
where does Ewings sarcoma affect
flat bones or mid shaft of bone e.g. pelvis, chest wall, vertebra
x ray in ewings sarcoma
‘moth eaten’ appearance
cortical thickening
list causes of microcyctic anaemia
- iron deficiency
- thalassamia major or trait
- anaemia of chronic disease
list causes of macrocytic anaemia
folate deficiency
vit B12 deficiency
diamond blackfan anaemia
liver disease
hypothyroidism
list causes of red cell aplasia (absent or reduced red cell precursors)
- diamond blackfan anaemia
- parvovirus induced red cell aplasia
- transient erythroblastopenia of childhood
presentation of diamond blackfan anaemia
autosomal dominant
1. craniofacial abnormalities - cleft palate
2. thumb abnormalities - hypoplastic, triphalangeal
3. growth restriction
4. red cell aplasia
investigations for diamond blackfan anaemia
- macrocytic anaemia with low reticulocyte count
- normal WCC
- increased HbF
- raised eADA
- bone marrow biopsy * - reduced erythroid precursors
cause of iron deficiency anaemia
- reduced dietary intake - found in red meat, green veg, if drink unfortified milk
- malabsorption - coeliac disease, post gastrectomy, h.pylori
- blood loss - worms, cancers, ulcers, menorrhagic
where is iron absorbed
absorbed in duodenum and upper jejunum
regulated by hepcidin (made in liver)
presentation of iron deficiency anaemia
fatigue, lethargy
SOB
headahce
palpitations
hair loss
angular stomatitis and atrophic glossitis
koilonychia ***
investigations reveal in iron deficiency anaemia
microcytic hypochromic anaemia
low serum iron and high transferrin = iron deficiency
low serum iron and low transferrin = chronic disease
blood test results for haemolysis
anaemia
high reticulocytes
high LDH
high unconjugated bilirubin
reduced haptoglobin
indicators intravascular vs extravascular haemolysis
intravascular- increased fragmented RBC and high LDH
inheritance of sickle cell disease
autosomal recessive
cause of sickle cell disease
point mutation of position 6 on beta globin gene (gluatmine -> valine)
results in formation of HbS which is insoluble and rigid
HbS polymerises in low oxygen tension and forms sickle cells which can cause occlusion and thrombosis
protective factors in sickle cell
alpha thalassamie trait
increased fetal Hb
presentation of sickle cell disease
- chronic haemolytic disease
- increased risk of infections for encapsulated organisms e.g. salmonella, pneumococcus - most common in early childhood
- jaundice
describe sickle cell crises
- VASO-OCCLUSIVE CRISES
painful dactylitis - PAINFUL CRISES - common presentation
swelling of fingers or toes, precipitated by infection dehydration, stress - ACUTE CHEST CRISES
pleuritic chest pain, fever - SPLENIC OR HEPATIC SEQUESTRATIONS
splenic enlargement, abdo pain - APLASTIC CRISES
- CEREBRAL INFARCTION
risk factors for painful crises
increased haematocrit or reduced fetal haemoglobin
management of painful crises
dexamethasone - shorten episodes of pain
PO opiates
diagnosis of sickle cell
high performance liquid chromatography *
CXR
new born screening !!! Hb electrophoresis
howell jolly bodies indicate hyposplenism
management of sickle cell disease
- prophylactic penicillin
- folic acid
- vaccinations
- hydroxycarbamide/ hydroxyurea (inhibits ribonucleopeptide reductase) - increases HbF levels, prevents vaso occlusive crisis
- monthly transfusions
- monoclonal antibody (crizanlizumab)
management of vaso-occlusive crises
- analegsia
- IV fluids
- oxygen
- exchange transfusion
- IV antibiotics
inheritance of thalassaemia
autosomal recessive
describe alpha thalassaemia
deletion of alpha globin on chromosome 16
alpha thalassaemia trait = deletion 12 genes -> asymptomatic
describe beta thalassaemia
mutation in beta globin gene on chromosome 11
HbF compensates for absent beta globin gene until about 6 months old when fully transition to HbA
beta thalassaemia minor- asymptomatic - reassure
beta thalassaemia major - present 3-6 months, severe anaemia, jaundice, skull bossing
diagnosis of beta thalassaemia
high performance liquid chromatography **
blood results indicating beta thalassaemia
microcytic anaemia
high HbF
anaemia
normal ferritin
blood film - target cells, red cell fragments, microcytic, hypochromic
management of beta thalassaemia major
regular blood transfusions every 3-6 weeks
deforoxamine (iron chelation)
CURE = STEM CELL TRANSPLANT
inheritance of hereditary spherocytosis
autosomal dominant - common in northern europe
pathophysiology in hereditary spherocytosis
- defect in gene for spectrin ** or ankyrin which make up erythrocyte cytoskeleton
2.loss of membrane surface - causes sphering of RBCS
- more prone to haemolysis and spherocytic red blood cells destroyed prematurely in the spleen (life span =28 days)
presentation of hereditary spherocytosis
chronic haemolytic anaemia (parvovirus can precipitate aplastic crises)
jaundice + neonatal jaundice (unconjugated)
gallstones
splenomegaly
investigations for hereditary spherocytosis
FBC - anaemia
increased reticulocyte count
blood film - spherocytes + reticulocytes
unconjugated bilirubinaeamia
negative DAT
management of hereditary spherocytosis
- folate supplementation
- blood transfusions
- vaccinations
- splenectomy > 6 yo
diagnosis of pyruvate kinase deficiency
blood film - prickle red cells
pyruvate kinase levels reduced
function of VWF
- Carrier protein for factor VIII
- attaches platelets to sub endothelium following vessel injury
secreted by endothelial cells + stored in weibel palade bodies
cause of VWF deficiency
AR or AD - defect in VWF gene on chromosome 12
presentation of VWF disease
mucosal bleeding
menorrhagia
epistaxis
prolonged bleeding
easy bruising
diagnsostic tests for VWF disease
- low platelets - in type 2b
- increased bleeding time - increased APTT
- VWF ristocetin cofactor assay
- factor vIII deficiency
mechanism of action of tranexamic acid
inhibit conversion of plasminogen to plasmin and prevents breakdown of fibrin clots
what is DIC
excessive upregulation and activation of clotting system leading to excess fibrin clots
caused by sepsis , trauma, malignancy
blood results in DIC
increased PT
increased APTT
reduced platelets
increased fibrinogen
anaemia
reduced platelets
cause of HUS
toxin related endothelial injury, thrombus formation and increased platelet consumption
presentation of ITP
1-4 weeks after URTI or live vaccines
petechiae
epistaxis
gingival bleeding
menorrhagia
cause of ITP
splenic destruction of antibody coated platelets
development of autoantibodies (IGA or IgG) to platelet membrane surface (GPiib/IIa)
management of ITP
- diagnosis of exclusion - blood film to exclude
- avoid contact sports
- reassure and usually resolves spontaneously
- avoid aspririn and ibuprofen
- can use pred or transexamic acid or IV IG
- monoclonal antibody rituximab is resistant ITP
list inherited platelet disorders
- bernard soulier syndrome
- may hegglin anomaly
- glanzmann thrombasthenia
- wiskott aldrich syndrome
inheritance of haemophilia
X linked recessive
difference between haemophilia A and B
haemophilia A - deficiency in factor vIII
haemophilia B - deficiency in factor IX (vit K dependent)
Presentation of haemophilia
haematoma at delivery
intracranial bleeding at delivery
excessive bleeding
epistaxis, joint bleeding
excessive bruising
diagnostic tests for haemophilia
- factor vIII or IX deficiency (SEVERE <1%)
- prolonged APTT
management of haemophilia
- genetic screening
- desmopressin
- recombinant factor complex as prophyalxis (can develop inhibitors)
- s/C vaccinations - avoid IM due to risk of haematoma
inheritance of G6PD deficiency
X linked recessive
presentation of G6PD deficiecny
acute haemolytic crisis in response to certain medications and FAVISM (fava beans)
neonatal jaundice
drugs causing haemolytic crisis in G6PD deficiency
quinines
sulphonamides (co-trimoxazole)
nitrofurantoin
chloramphenicol
vit K
aspirin
investigations for G6PD deficiency
indirect bilirubin rise
LDH rise
Hb reduced
redd cell G6PD levels reduced
peripheral smear - heinz bodies, bite cells, polychromasia
complication of neuroblastoma
paraneoplastic syndrome - antibdoies formed against neuroblastoma cells targets cerebellar neurones and causes ataxia
describe bernard soulier syndrome
deficiency of VWF glycoprotein IB-IX-V receptor
autosomal recessive
thrombocytopenia + large plataletes + increased bleeding time
what does ionising radiation do to DNA
electron displacement resulting in double stranded breaks in DNA and apoptosis
describe mantoux test
type IV hypersensitiity test
intradermal
function of macrophage
detection, phagocytosis and destruction of bacteria
reasons for not being to donate blood
travel to endemic area in last 6 months
any blood transfusions
organ transplant (risk of creutz felt jacob disease)
deferred for 3 months after body piercing or tattoos
< 17 y/o
< 50kg
pathophysiology of alpha thalassaemia
defective mRNA that causes reduced or absent synthesis of alpha globin genes resulting in loss 3 alpha globin genes
describe neonatal alloimmune thrombocytopenia
platelet antigens inherited from mother and father
if mother exposed to fetal antigens from the father that she does not have, she will produce antibodies against them
these antibdoies cross the placenta and then attack the paternal antigens in the fetus which can cause low platelet count at birth
= maternal antibodies to paternal inherited HPA-1a in the baby
describe evans syndrome
thrombocytopenia + autoimmune haemolytic anaemia
cause of aplastic anaemia
medications - chloramphenicol
parvovirus
diagnosis = bone marrow aspiration = peripheral blood macrocytosis
