Haematology Flashcards
How can you tell if an anaemia is caused by an issue with removal or production of RBCs
measure reticulocyte count
Causes of microcytic anaemia
iron deficiency
thalassaemia
anaemia of chronic disease
sideroblastic anaemia
causes of normocytic anaemia
acute blood loss anaemia of chronic disease CKD autoimmune rheumatic disease Endocrine disease haemolytic anaemia
Causes of macrocytic anaemia
vitamin B12 or folate deficiency alcohol liver disease hypothyroidism drug therapy e.g. azathioprine
How is iron absorpbed
intestinal haem transporter HCP1 actively transports iron into the duodenal epithelial cells where some binds to ferritin (intracellular store) and the rest circulates in blood bound to transferrin.
How is iron used
majority in haemoglobin
the rest in reticuloendothelial cells, hepatocytes and skeletal muscle cells as ferritin or haemosiderin
Serum test results in iron deficiency
low serum iron
high total-iron binding capacity
increase in transferrin receptors
low reticulocyte count
Treatment of iron deficiency
usually find a cause first
ferrous sulphate oral
ferrous gluconate if bad SE
parenteral iron (IV iron or IM iron) only in extreme cases.
what is anaemia of chronic disease
bone marrow is sick
second most common cause of anaemia and common in hospitalised patients
usually normocytic
Common causes of anaemia of chronic disease
tuberculosis crohns rheumatoid arthritis SLE malignant disease
what is pernicious anaemia
autoimmune disorder in which parietal cells of stomach are attacked resulting in atrophic gastritis and the loss of intrinsic factor production and hence b12 malabsorption
where is b12 absorped
terminal ileum using intrinsic factor (produced by parietal cells in stomach)
risk factors for pernicious anaemia
elderly
female
fair haired
autoimmune disease
Treatment for pernicious anemia
b12 injections (IM hydroxocobalamin)
how might you distinguish between a folate and b12 deficiency
no neuropathy in folate deficiency
treatment of folic acid deficiency
folic acid tablets WITH B12 unless known to be normal as can precipitate subacute combined degeneration of the cord
main causes of haemolytic anaemia
RBC membrane defects - hereditary spherocytosis
enzyme defects - glucose-6-phosphate dehydrogenase deficiency
haemoglobinopathies:
B thalassaemia
A thalassaemia
sickle cell disease
autoimmune haemolytic anaemia
features of haemolytic aneamia (bilirubin)
high unconjugated bilirubin high urobilinogen high stercobilinogen (dark stool) splenomegaly bone marrow expansion reticulocytosis
hereditary spherocytosis summary
autosomal dominant
deficiency in structural protein spectrum
sphere shaped RBC get stuck in spleen and cause premature haemolytic and splenomegaly
presentation of hereditary spherocytosis
jaundice at birth can have delayed jaundice anaemia splenomegaly ulcers on leg gall stones
aplastic anaemia after infections (particularly parvovirus)
treatment of hereditary spherocytosis
splenectomy delayed until after childhood (risk)
post-op life-long penicillin prophylaxis
G6PD deficiency summary
heterogenous x-linked (more common in males)
G6DP reduces NADP to NADPH which is essential for protecting RBCs from oxidative stress
Leads to reduced RBC lifespan
Presentation of G6PD deficiency
asymptomatic
drug-induced haemolytic: aspirin antimalarials (quinine, chloroquine) nitrofuratonin fava beans
In attacks:
rapid anaemia
jaundice
Results/treatment of G6DP attacks
irregular cells on film Bite cells (cells with indentation in) reticulocytosis G6PD enzyme levels will be low but can be falsely high blood transfusion may be life saving
What are the types of haemoglobin
HbA foetal Hb (HbF) Hb delta (HbA2)
In an adult
HbA - 97%
HbA2 - 2%
HbF - 1%
What is the normal production of alpha and beta chains
1:1 ratio
HbA has 2 alpha and 2 beta
Beta thalassaemia summary
reduced B chain production results in excessive alpha chains.
Excess alpha chains bind with any delta or gamma chains available and oriduce excess Hb delta and foetal Hb
IF HETEROZYGOUS THEN ASYMPTOMATIC OR MILD ANAEMIA
Mutations in beta thalassaemia
Point mutations
Mutations in alpha thalassaemia
gene deletions
summary of alpha thalassaemia
four gene deletion - no alpha chain synthesis
only Hb Parts (4 gamma chains) is present
incompatible with life
stillborn infant or die very shortly after birth - hydrops fetalis
three gene deletion - reduction in alpha synthesis, HbH has 4 beta-chains, moderate anaemia
two gene deletion - microcytosis mild anaemia
one gene deletion - normal
inheritance of sickle cell trait
autosomal recessive
when does sickle cell present
after 6 months as foetal haemoglobin is normal (no beta chains)
mutation of sickle cell
single base mutation on beta chain
complications of sickle cell disease
vaso-occlusive crises:
pain in hands/feet in chidlren
long bone pain in adults (femur, spine, ribs) due to avascular necrosis of bone marrow
acute chest syndrome
vaso-occlusive crisis of pulmonary vasculature
pulmonary hypertension and chronic lung disease are the most common cause of death in adults with sickle cell
Treatment for sickle cell
vaccinate - prevent infection
folic acid to all haemolytic patients
attacks - fluids, analgesia, oxygen, antibiotics
blood transfusion for acute chest syndrome, aplastic crisis
ORAL HYDROXYCARBAMIDE to increase HbF concentration
Aplastic anemia definition and causes
pancytopenia (all major blood cell lines)
Idiopathic Fanconi's anaemia benzene, toluene and glue sniffing chemo drugs antibiotics - carbamazepine, azathioprine and chloramphenicol infections: EBV, HIV TB
clinical presentation of aplastic anaemia
obvious: anaemia infections bleeding bleeding gums, bruising
DD: other causes of pancytopenia - drugs, lymphomas, myeloma, SLE
treatment of aplastic anaemia
broad spectrum antibiotics
red cell and platelet transfusion
bone marrow transplant
polycythemia vera
Janus kinase 2 mutation
clonal stem cell disorder causing excessive proliferation of RBCs, EBCs and platelets causing a raised haematocrit and viscosity
Clinical presentation
vague hyper viscosity symptom headache itching tiredness dizziness tinnitus visual disturbance severe itching when warm gout hypertension hepatosplenomegaly
treatment of polycythemia vera
venesection weekly - 500ml
chemotherapy - hydroxycarbamide for those who don’t tolerate venesection
++ low dose aspirin
What is ITP
thrombocytopenia due to immune destruction
bruising epistaxis menorrhagia purpura gum bleeding
What is primary ITP
acute in children (2-6)
recent viral infection. e.g. chickenpox
self limiting purport usually on legs
What is secondary ITP
chronic in adults
women and often associated with autoimmune disorders such as SLE, thyroid disease
CLL and HIV infection.
Treatment of ITP
prednisolone
IV IgG if going into surgery as this will raise the platelet count more rapidly
second line: splenectomy
What is thrombotic thrombocytopenia purpura TTP
widespread adhesion and aggregation of platelets. due to a deficiency in a protease than breakdown vWF
Causes of TTP
idiopathic autoimmune (SLE) cancer pregnancy drug associated (quinine)
Clinical presentation of TTP
florid (red) purpura
fever
fluctuating cerebral dysfunction
haemolytic anaemia
Treatment for TTP
plasma exchange
IV methylprednisolone
IV rituximab
Low platelets but do not give as in hypercoaguable state!!!
would you see schistocytes in ITP or TTP
TTP think clots tear apart RBCs causing fragmentation
Which is more serious ITP or TTP
TTP! it is an emergency as blood is clotting! but do a plasma exchange.
Can leave ITP if asymptomatic
How does DIC arise
systemic activation of coagulation either by release of procoagulant material such as tissue factor or via cytokine pathways as a part of the inflammatory response.
caused by extensive damage to vascular endothelium exposing tissue factor or enhanced expression of tissue factor by monocytes in response to cytokines
Conditions associated with DIC
sepsis major trauma and tissue destruction advanced cancer obstetric complications pancreatitis
Clinical findings in DIC
severe thrombocytopenia
elevated fibrin degradation products - d-dimer
fragmented RBCs on film
prolonged PT
Treatment for DIC
treat cause
platelet transfusion
FFP to replace coat factors
What should you monitor after starting Heparin
platelet levels as can get heparin induced thrombocytopenia
most common ages for ALL
2-4 years old
which cells does ALL affects
T and B precursors
all B cells - children
all T cells - adult
Diagnosis of ALL
high WCC
blast cells on film and in bone marrow
CXR/CT may show lymphadenopathy
treatment for ALL
blood transfusion prophylactic antibac/fung allopurinol prevents tumour lysis syndrome chemo marrow transplant
Symptoms of AML
anaemia - fatigue, claudication, breathlessness, pallor and cardiac flow murmur
infection - fever and mouth ulcers
low platelets - bleeding, bruising
gum hypertrophy
hepatomegaly/splenomegaly
treatment for AML
blood and platelet transfusion infection prophylaxis allopurinol to prevent tumour lysis syndrome chemo marrow transplant
age group for CML
40-60 years, male predominance
more than 80% have the Philadelphia chromosome
diagnosis for CML
very high WCC - whole spectrum of myeloid cells increased, neutrophils, basophils, eosinophils
low HB
low platelets
hypercellular bone marrow
treatment for CML
IMATINIB
tyrosine kinase inhibitor (Philadelphia chromosome linked to increase TK activity which stimulates cell division)
age range for CLL
the most common leukaemia
presents in later life - elderly
CP of CLL
asymptomatic often an incidental finding
diagnosis of CLL
normal/low hb
raised WCC w/ very high lymphocytes
smudge cells on blood film
outlook for CLL
rule of 3s
1/3 never progress
1.3 slowly
1/3 quickly
treatment for CLL
human IV immunoglobulins
chemo
blood transfusion
Hodgkins lymphoma
Reed-Sternberg cells
male predominance
teenagers 13-19 and over 65s
EBV plays a role
CP of Hodgkins lymphoma
cervical lymphadenopathy (rubbery) B symptoms
emergency presentation:
infection
SVC obstruction
blackouts
diagnosis of Hodgkins lymphoma
CT/MRI for staging (Ann Arbor)
lymph node excision or bone marrow biopsy for Reed-Sternberg cells
PET scan
Ann Arbor staging
I confined to single lymph node
II involvement of two or more lymph node regions on same side of diaphragm
III involvement of nodes on both sides of the diaphragm
IV spread beyond lymph to liver or bone
A: no systemic symptoms (other than itching)
B: B symtpoms
Non-Hodgkin’s lymphoma
all lymphomas without reed-sternberg
80% is B cell origin
strong link with EBV and Burkitts lymphoma
two grades of non-hodgkins
low grade - follicular lymphoma
(incurable, slow growing around 11 year survival)
high grade - diffuse large B-cell lymphoma
treatment of non-hodgkins
R-CHOP regimen Rituximab Cyclophosphamide Hydroxy-daunorubicin Oncovin Prednisolone
May also use radiotherapy
what is myeloma
cancer of differentiated B cells (PLASMA CELLS) which produce antibodies. accumulate in the bone marrow and cause failure
peak age 70
presentation of myeloma
OLD CRAB OLD age Calcium elevated Renal failure Anaemia Bone lytic lesions (activate osteoclasts and inhibit osteoblasts)
signs of myeloma
normocytic normochromic anaemia raised ESR Rouleaux formation on blood film (RBC stack like coins) hyperclacaemia pepper-pot skull vertebral collapse
treatment of myeloma
analgesia for bone pain (avoid NSAID renal) bisphosphonates transfusion/EPO injection chemo stem cell transplant
what is febrile neutropenia
temp above 38 in a patient with neutrophils <1x10^9
life threatening emergency
basically infection in someone with neutropenia
risk factors for febrile neutropenia
chemo <6 weeks ago aplastic anaemia autoimmune disease leukaemia methotrexate carbimazole clozapine
treatment of febrile neutropenia
broad spectrum antibiotics immediately
which cancers most commonly cause malignant spinal cord compression
myeloma
lymphoma
management of malignant spinal cord compression (caudal equine)
quick!
bed rest
dexamethasone
urgent MRI spine
what is tumour lysis syndrome
malignant cells breakdown quickly:
high uric acid
hyperkalaemia
hyperphosphatemia
hypocalcaemia
complications of tumour lysis syndrome
neuro (hypocalcaemia):
muscle cramps, seizure
cardiac (hyperkalaemia)
arrest
renal (uric acid crystals)
failure
treatment of tumour lysis syndrome
allopurinol reduces uric acid levels to prevent kidney failure
monitor electrolytes
dialysis if needed
clinical presentation of hypercalcaemia
bones moans stone psychiatric groans
confusion boe pain constipated nausea polyuria renal stones abdo pain shortening of QT interval
treatment of hypercalcaemia
hydration 3-4L/day
bisphosphionates (takes a few days to effect)
how to reverse heparin
protamine
reversal of warfarin
immediate - fresh frozen plasma FFP
vitamin K will reverse slowly
when would heparin be used
bypass surgery
when is LMW heparin used
SC injection
treatment and prophylaxis
what is the normal target INR
2-3
which clotting factors are vitamin K dependent
1972
II, VIII, IX and X
(1 is a 10)
which clotting factors do NOACs affect
II or X
when would NOACs be used
AF, DVT, PE
when would warfarin be preferred over NOAC
mechanical heart valves as NOAC does not allow for exact control over INR
OR
pregnancy
what is the action of rivaroxaban/apixaban
factor Xa inhibitor
what is the antibiotic therapy of choice for neutropenic sepsis
piperacillin and tazobactam
what is the most common thrombophilia
factor V Leiden - causes mutation in factor V resulting in resistance to inactivation by protein C.
What does protein C do
negative feedback on clotting cascade
