haematology Flashcards
Haematological diseases and their risk factors, pathology, clinical signs, diagnosis, and treatment.
causes of microcytic anaemia
iron deficiency
chronic disease
thalassaemia
vitamin B6 deficiency
how many menstruating women get iron deficiency anaemia?
15%
microcytic anaemia blood film
small erythrocytes
pathology of microcytic anaemia
low MCV
blood loss
malabsorption
hookworm
clinical sign of microcytic anaemia
koilonychia (spoon nails)
diagnosis of microcytic anaemia
blood film - microcytic
ferritin test
gastroscopy
treatment of microcytic anaemia
oral iron/ferrous sulfate
normal Hb range for males
131 - 166 g/L
normal Hb range for females
110 - 147 g/L
complications of anaemia
myocardial fatty change fatty change in liver angina claudication skin and nail atrophy CNS cell death
normal MCV
80-100 fl
how many men are affected by normocytic anaemia?
44% of men over 85
causes of normocytic anaemia
acute blood loss
chronic disease
combined haematinic deficiency
pathology of normocytic anaemia
normal MCV acute blood loss anaemia secondary to chronic bone disease bone marrow failure renal failure hypothyroidism haemolysis pregnancy
diagnosis of normocytic anaemia
normal MCV but decreased haemoglobin and haematocrit
causes of macrocytic anaemia
B12/folate deficiency
alcohol (liver disease)
hypothyroid
haematological (rare) - genetic disease
diagnosis of macrocytic anaemia
high MCV on blood film
Schilling test
IF/coeliac antibodies
causes of folate deficiency
poor diet malabsorption increased demand (e.g. pregnancy) medications high exposure to UV
clinical sign of folate deficiency
macrocytosis
symptoms of folate deficiency
loss of appetite weight loss weakness heart palpitations megaloblastic anaemia
diagnosis of folate deficiency
blood film
treatment of folate deficiency
improve diet
oral vitamin supplements
treat specific cause if secondary
complications of folate deficiency if pregnant
neural tube defect in baby
risk factors for sickle cell anaemia
family history (recessive autosomal) African descent
pathology of sickle cell anaemia
HbS polymerises when deoxygenated
deformation of erythrocytes
blockage of small vessels
signs of sickle cell anaemia
microvascular occlusion
symptoms of sickle cell anaemia
muscle and bone pain
strokes
vaso-occlusive crisis - pain
triggered by cold
treatment of sickle cell anaemia
transfusion in aplastic crisis hydroxycarbamide (increase in HbF) prophylactic active artificial immunity antibiotics genetic counselling
complications of sickle cell anaemia
aplastic crisis chronic renal failure sequestration crisis (atrophic spleen) splenic infarction (immune-compromisation) sickle cell chest syndrome
causes of autoimmune haemolytic anaemia
broadly idiopathic
can be secondary to another disease
pathology of autoimmune haemolytic anaemia
antibody mediated phagocytosis of erythrocytes
signs of autoimmune haemolytic anaemia
breathlessness
diagnosis of autoimmune haemolytic anaemia
rule out other causes of anaemia
evidence of haemolysis
serological tests
Coomb’s test
treatment of autoimmune haemolytic anaemia
blood transfusion
splenectomy
immunosuppressant (e.g. rituximab)
if secondary, treat primary illness
type of antibodies involved in autoimmune haemolytic anaemia
IgG and IgM
causes of thrombosis
Virchow’s triad:
changes in vessel surface
changes in blood flow
changes in blood constituents
why is thrombosis more likely after surgery or an MI?
blood flow is slower
thrombus definition
solid mass of blood constituents formed within the vascular system in life
venous thrombosis is most commonly due to
stasis
why are immobile patients more likely to get thrombosis?
muscular pressure decreases –> venous return also decreases
thrombophlebitis
the inflammatory reaction when a vein is thrombosed
phlebothrombosis
when an inflamed vein forms a thrombus
pathology of arterial thrombosis
usually superimposed on atheroma
generates turbulence –> loss of intimal cells –> clot formation with fibrin deposition and platelet clumping
propagation
thrombi grow in the direction of blood flow
signs of thrombosis
local pain and local inflammation
treatment of thrombosis
anticoagulants (aspirin, warfarin)
complications of arterial thrombosis
distal tissue infarction
complications of venous thrombosis
oedema
embolism
leukaemia risk factors
smoking
ionising radiation
Down’s syndrome
prior chemotherapy
who does acute myeloid leukaemia tend to affect?
older people who have had treatment for other cancers
who does ALL tend to affect?
young children
what does leukaemia come from?
haematopoietic stem cells
subtypes of leukaemia
acute lymphoblastic leukaemia
chromic lymphoblastic leukaemia
acute myeloid leukaemia
chronic myeloid leukaemia
which mutation is associated with chronic myeloid leukaemia?
Philadelphia translocation
where does tumorigenesis occur in leukaemia?
bone marrow
signs of leukaemia
petechiae (easy bruising) enlarged spleen/liver fever pale skin low platelet count anaemia immune suppression (--> sores and opportunistic infection) neurological symptoms
acute leukaemia diagnosis
> 20% of WBCs in marrow are blasts
what can indicate leukaemia relapse before anything else?
MRD testing
diagnosis of leukaemia
lymph node biopsy
XR and MRI
FBC
bone marrow biopsy
treatment for acute myeloid leukaemia
chemotherapy
what can be used to treat some variations of leukaemia?
tyrosine kinase inhibitors
treatment for leukaemia
chemotherapy
bone marrow transplant
targeted therapy
differential diagnosis for acute leukaemia
post operative changes
sepsis
who does Hodgkin’s lymphoma affect?
bimodal peak (young and old)
risk factors for lymphoma
HIV
EBV
HTLV-1
H.pylori
what cells are present in Hodgkin’s lymphoma?
Reed-Sternberg cells
lymphoma
cancerous proliferation of lymphocytes predominantly in lymph nodes, but can present anywhere in the body
signs of lymphoma
compression syndromes
symptoms of lymphoma
fatigue lump nodal disease night sweats weight loss
diagnosis of lymphoma
lymph node biopsy bone marrow biopsy flow cytometry immune-phenotyping blood films PET scan blood test
first line treatment for lymphoma
watch and wait
treatment for Hodgkin’s lymphoma stage 1-2
combination chemotherapy and radiotherapy
treatment for Hodgkin’s lymphoma stage 3-4
long term combination chemotherapy
treatment for low grade non-Hodgkin’s lymphoma
radiotherapy and monoclonal antibodies
treatment for high grade non-Hodgkin’s lymphoma
combined chemotherapy and monoclonal antibodies (rituximab or zevalin)
complications of lymphoma treatment
infertility
rituximab
monoclonal antibody that is anti-CD20 (CD20 is found on B cells)
multiple myeloma
cancerous condition of bone marrow plasma cells
risk factors for multiple myeloma
MGUS protein in blood
obesity
pathology of multiple myeloma
cloned malignant plasma cells produce immunoglobulins
high osteoclast activity
light chain deposition in kidneys
clonal expansion –> MGUS –> early myeloma (smouldering myeloma) –> late myeloma and end organ damage
symptoms of multiple myeloma
bone pain bleeding frequent infections tiredness malaise
signs of multiple myeloma
CRAB Calcium (high) Renal Anaemia Bone disease
diagnosis of multiple myeloma
Rouleaux stacks - aggregated RBCs in blood film
high ESR
monoclonal protein in blood and urine (Bence Jones protein)
light chain deposition in kidneys
pepper pot skull
evidence of bone marrow plasma cells in excess of 10%
treatment of multiple myeloma
thalidomide
dexamethasone
stem cell replacement therapy
radiotherapy
complications of multiple myeloma
peripheral neuropathy (may be from treatment) amyloidosis infection (main cause of death from MM)
malaria vector
female anopheles mosquito
Malaria falciparum causes what percentage of malaria cases?
50%
signs of malaria
flu-like symptoms haemolytic anaemia fever jaundice paroxysm (sudden changes between hot and cold) can be cerebral enlarged spleen high bilirubin low platelet count
diagnosis of malaria
antigen RDT
thick and thin blood films
malaria treatment
PO quinine
primaquine for hypnozoite clearance (check G6PD/pregnancy status)
complication of Malaria malariae
quartan fever
risk factors for polycythaemia
dehydration hypertension obesity smoking hypoxia altitude lung disease cyanotic heart disease inappropriate increased EPO secretion
primary polycythaemia
polycythaemia rubra vera
95% of cases of polycytheamia are associated with which mutation?
JAK2 mutation
pathology of polycythaemia
clonal proliferation of haematopoietic myeloid stem cells in the bone marrow which retain the ability to differentiate into erythrocytes
polycythaemia
too many red blood cells
relative polycythaemia
decrease in plasma volume
normal RBC mass
absolute polycythaemia
increase in RBC mass
normal plasma volume
can be primary of secondary
signs of polycythaemia
splenomegaly
facial plethora
thrombosis
symptoms of polycythaemia
headaches dizziness tinnitus burning sensation in fingers and toes itching
diagnosis of polycythaemia
raised red cell mass on 51Cr studies and splenomegaly in the setting of a normal PaO2 is diagnostic
decreased serum EPO
FBC results for patient with polycythaemia
increased RCC increased Hb increased HCT increased PCV ± increased WBCs and platelets
treatment of polycythaemia
aim to keep HCT <0.45 to decrease thrombosis risk aspirin alpha-interferon venesection bone marrow suppressive drugs
risk factors for haemophilia
x-linked inheritance pattern - therefore greater risk for males
30% new mutations
cause of haemophilia A
factor VIII deficiency
cause of haemophilia B
factor IX deficiency
symptoms of haemophilia
bleeding into joints
severe arthropathy
haematomas
diagnosis of haemophilia
increased APTT
decreased factor assay
treatment of haemophilia
genetic counselling
recombinant factors
desmopressin
avoid NSAIDs
acquired haemophilia
a bleeding diathesis causing big mucosal bleeds
caused by antibodies that suddenly appear and interfere with factor VIII
risk factors for Von Willebrand’s disease
genetic - autosomal dominant or recessive
pathology of Von Willebrand’s disease
decreased VWF
signs of Von Willebrand’s disease
platelet disorder signs
bruising
epistaxis
menorrhagia
diagnosis of Von Willebrand’s disease
increased APTT
increased bleeding time
decreased clotting factors
decreased VWF
treatment or Von Willebrand’s disease
desmopressin
VWF concentrate given for surgery
risk factors for immune thrombocytopaenia
pregnancy female viral infection (primary) cancer (secondary) HIV (secondary)
immune thrombocytopaenia pathology
anti platelet autoantibodies coat platelets
who does acute immune thrombocytopaenia affect?
children, following an infection
who does chronic immune thrombocytopaenia affect?
women
signs of immune thrombocytopaenia
petechiae
symptoms of immune thrombocytopaenia
bleeding epistaxis menorrhagia purpura bruising haematomas
complications of immune thrombocytopaenia
subarachnoid haemorrhage
intracerebral haemorrhage
diagnosis of immune thrombocytopaenia
megakaryocytic in marrow
anti platelet auto-antibodies
treatment of immune thrombocytopaenia
IV immunoglobulin (to temporarily raise platelet count) rituximab tranexamic acid inhibits breakdown of fibrin (may help with the bleeding)
risk factors for thrombotic thrombo-cytopaenic purpura (EMERGENCY)
lupus
secondary
often idiopathic
pathology of thrombotic thrombocytopenic purpura
reduction of a protease which chops VWF in half before entering circulation –> bit bits of VWF stick to platelets –> extensive microscopic clots in small vessels of the body causing low platelet count
results in multi-organ damage
signs of thrombotic thrombocytopaenic purpura
fever changes in mental status thrombocytopaenia reduced renal function haemolytic anaemia hypertension
symptoms of thrombotic thrombocytopaenic purpura
tiredness confusion headaches seizures stroke-like episodes
which protease is deficient in thrombocytopaenic purpura?
ADAMTS13
diagnosis of thrombocytopaenic purpura
thrombotic microangiography
genetic tests for abnormal ADAMST13 genes
treatment of thrombocytopaenic purpura
plasma exchange
glucocorticoids
rituximab
cyclophosphamide
complications of thrombocytopaenic purpura
sudden death (often within 24hrs)
thalassaemia
abnormal erythrocytes due to unequal amount of Hb chains
what may carriers of thalassaemia have?
slightly smaller RBCs
risk factors for thalassaemia
genetic
pathology of thalassaemia
unbalanced production of Hb chains - divided into alpha and beta thalassaemia
when does beta thalassaemia major present?
when the child stops making foetal Hb
signs of thalassaemia
splenomegaly
yellow skin
slow growth in children
bone problems
symptoms of thalassaemia
tiredness
pale skin
diagnosis of thalassaemia
FBC MCV blood film HbF electrophoresis
complications of thalassaemia
blood transfusions may cause iron overload –> iron deposition in organs –> haemachromatosis
e.g. myocardial siderosis from iron overload (do MRI to diagnose)
treatment of thalassaemia
blood transfusions
splenectomy
hormonal replacement
marrow transplant (chance of cure)
pathology of neutropenia due to underproduction
marrow failure
marrow infiltration
marrow toxicity
pathology of neutropenia due to increased removal
autoimmune
Felty’s syndrome
cyclical
common cause of neutropenia
chemotherapy
