haematology Flashcards
plasma cell dycrasias
a spectrum of progressively more severe monoclonal gammopathies in which a clone or multiple clones of pre-malignant or malignant plasma cells over-produce and secrete an abnormal monoclonal antibody into the blood stream
2 examples of monoclonal gammopathy of undetermined significance (MGUS)
plasmacytomas:
- tumours consisting of abnormal plasma cells
- myeloma
- solitary, multiple solitary or extramedullary plasmacytoma
Waldenstrom’s macroglobulinaemia:
-IgM related
MGUS
myeloma protein (abnormal antibody) is found in the blood
MIg <30g/L
no significant increase in bone marrow plasma cells
no organ impairment
CAN LEAD TO MULTIPLE MYELOMA
multiple myeloma
neoplastic proliferation of bone marrow plasma cells
multiple myeloma: characteristics
monoclonal protein in serum or urine
lytic bone lesions
excess plasma cells in bone marrow
CRAB end organ damage- calcium, renal, anaemia, bone
multiple myeloma: pathogenesis
- accumulation of malignant plasma cells in bone marrow causes it to fail
- the malignant cells produce excess of one type of immunoglobulin (IgG=55%, IgA=20%)
- low variety of Ig causes immunosuppression
multiple myeloma: epidemiology
average age of diagnosis =70
more common in afro-caribbeans
1% of all cancers
13% of haem cancers
multiple myeloma: incidence/prevalence
incidence= 40/million/year
prevalence 180-279/million
multiple myeloma: presentation OLD CRAB
old age
Calcium elevated
Renal failure, proteinuria
Anaemia- neutropenia or thrombocytopenia causes infection, bleeding, fatigue and pallor
Bone lytic lesions- back pain and fractures
multiple myeloma: FBC investigation
normocytic normochromic anaemia
raised ESR
rouleaux formation of blood film
multiple myeloma: U&E investigation
high calcium
high alkaline phosphatase
bence-jones protein present
multiple myeloma: imaging investigations
lytic lesions
pepper-pot skull
fractures
osteoporosis
multiple myeloma: bone marrow biopsy
increased plasma cells
multiple myeloma: cure or treatment
incurable disease
aim of treatment is to achieve plateau phase, control the symptoms and supportive measures
multiple myeloma: treatment
chemotherapy, steroids and bisphosphonates
treat end organ damage and infections
leukaemia
presence of rapidly proliferating immature blood cells (precursors of white or red) in the bone marrow that are non-functional
what does leukaemia cause
wasting energy on non-functioning cells
space taken up in bone marrow
bone marrow unable to produce normal cells
when bone marrow is filled, leukaemia cells enter blood
leukaemia: types
- Acute lymphoblastic leukaemia (ALL)= small lymphocyte that becomes B and T cells
- Acute myeloid leukaemia (AML)= myeloblast
- Chronic myeloid leukaemia (CML)= basophil, neutrophil, eosinophil
- Chronic lymphatic leukaemia (CLL)= B cells
leukaemia: risk factors
congenital- very rare, down’s syndrome (1-2% get AML)
environmental= radiotherapy, chemo, benzene/other chemicals
acute lymphoblastic leukaemia: epidemiology
common between 2-4 years old
most common cancer in childhood
if proliferation is all B cells- children
all T cells- adults
acute lymphoblastic leukaemia: presentation
- marrow failure (anaemia, thrombocytopenia, infection)
- bone marrow infiltration causes bone pain
- liver/spleen infiltration results in hepatosplenomegaly
- node infiltration causes lymphadenopathy
acute lymphoblastic leukaemia: investigations
FBC/blood film
CXR/CT to see for mediastinal and abdo lymphadenopathy
Lumbar puncture to see for CNS involvement
acute lymphoblastic leukaemia: treatment
blood/platelet transfusions treat infections IV fluids chemo marrow transplant ALLOPURINOL- prevents tumour lysis syndrome
acute myeloid leukaemia: epidemiology
most common leukaemia in adults
associated with radiation and Down’s syndrome
Progresses rapidly with death in 2 months if untreated
acute myeloid leukaemia: presentation
gum hypertrophy
hepatomegaly and splenomegaly
marrow failure- anaemia, thrombocytopenia, infection
acute myeloid leukaemia: diagnosis
WCC raised but can be low or normal
diagnosis depends on bone marrow biopsy but differentiation from ALL is based on microscopy and immunophenotyping
acute myeloid leukaemia: complications
infection is the major issue- septicaemia
acute myeloid leukaemia: treatment
blood/platelet transfusions treat infections IV fluids chemo marrow transplant ALLOPURINOL- prevents tumour lysis syndrome
chronic myeloid leukaemia: epidemiology
exclusively a disease of adults
mainly occurs between 40-60 years old
slight male predominance
80% have Philadelphia chromosome which has tyrosine kinase activity- stimulates cell division
chronic myeloid leukaemia: presentation
symptomatic anaemia splenomegaly- abdo discomfort weight loss palor fever gout due to purine breakdown
chronic myeloid leukaemia: diagnosis
blood count- high WCC, low Hb, low platelets
bone marrow aspirate- hypercellular
chronic myeloid leukaemia: treatment
stem cell transplant
oral imatinib- specific tyrosine kinase inhibitor
chronic lymphocytic leukaemia: epidemiology
most common leukaemia
mainly occurs late in life
genetic mutations influence risk
pneumonia can also be a triggering event
chronic lymphocytic leukaemia: presentation
often no symptoms
may be anaemic
if severe- weight loss, sweats, anorexia
enlarged, rubbery, non-tender nodes
chronic lymphocytic leukaemia: diagnosis
blood count- raised WCC with high lymphocytes
blood film- smudge cells seen in vitro
chronic lymphocytic leukaemia: complications
autoimmune haemolysis
increased infection due to low IgG
marrow failure
chronic lymphocytic leukaemia: progression
death is often due to complication of infections
may transform into aggressive lymphoma- Richter’s syndrome
chronic lymphocytic leukaemia: treatment
blood transfusion
stem cell transplant
chemo/radiotherapy
human IV immunoglobulins
chronic lymphocytic leukaemia: prognosis
rule of thirds
1/3 never progresses
1/3 progresses slowly
1/3 progresses quickly
lymphoma
disorder caused by malignant proliferations of lymphocytes
lymphoma: locations
accumulate in lymph nodes causing lymphadenopathy
can also be found in blood, bone marrow, liver and spleen
lymphoma: aetiology
most cases unknown
immunodeficiency- primary (e.g. ataxia telangiectasia) or secondary (e.g. HIV, transplants)
infections
autoimmune disorders
lymphoma: symptoms
loss of appetite
loss of weight
night sweats
lymphoma: signs
hepatosplenomegaly
lymph node enlargement
lymphoma: investigations
blood film and bone marrow
lymph node biopsy
immunophenotyping
imaging
lymphoma: assessing a patient
history/exam bloods CXR echo PFTs performance status
lymphoma: WHO performance status
0= asymptomatic
1=symptomatic but only restricted by strenuous activity
2= symptomatic <50% in bed during day
3= symptomatic >50% in bed but not bed bound
4=bed bound
5= death
lymphoma: subtypes
hodgkin’s
non-hodgkin’s
hodgkin’s lymphoma: presentation
painless
lymphadenopathy
(B symptoms) sweats, weight loss
hodgkin’s lymphoma: diagnosis
reed-sternberg cell: 4 histological subtypes
hodgkin’s lymphoma: stages
1= one place
2= 2 areas or more, same side of diaphragm
3= lymph nodes on both sides of diaphragm
4 spread to multiple places
A= absence of B symptoms
B=presence
hodgkin’s lymphoma: treatment
depends on stage
ABVD- adriamycin, bleomycin, vinblastine, dacarbazine
relapse responds to marrow transplant
hodgkin’s lymphoma: treating stage 1-2A
short course combo of chemo followed by radiotherapy
70-80% prolonged disease free survival
hodgkin’s lymphoma: treating stage 2B-4
combination chemotherapy
50-70% prolonged disease free survival
hodgkin’s lymphoma: late effects
infertility cardiomyopathy (anthracyclines) lung damage (bleomycin) peripheral neuropathy (vinca alkaloids) psychological issues
non-hodgkin’s lymphoma (NHL)
presentation, subtypes, treatments and outcomes have a much larger variety
low grade/indolent NHL
e.g. follicular lymphoma
slow growing
usually advanced at presentation
average survival is 9-11 years
low grade/indolent NHL: treatment
do nothing! alkylating agents purine analogues combination chemo monoclonal antibodies radiotherapy bone marrow transplant
high grade/aggressive NHL
e.g. diffuse large B cell lymphoma
usually nodal presentation but 1/3 have extranodal involvement
patients usually unwell with short history
high grade/aggressive NHL: treatment
early= short course chemo+radiotherapy
advanced= combination chemo and monoclonal antibodies
monoclonal antibodies
rituximab
anti-CD-20 targets CD20 expressed on cell surface of B cells
minimal side- effects
lump in the neck- differential diagnosis
infected or inflamed lymph nodes
malignant lymph nodes
thyroid
embryologic remnant
anaemia
reduced haemoglobin levels
normal haemoglobin ranges
male= 131-166g/L
female=110-147g/L
anaemia: acute consequences
reduced oxygen transport
tissue hypoxia
compensation- increased perfusion, oxygen transfer and red cell production
anaemia: pathological consequences
myocardial fatty change
fatty change in liver
skin and nail atrophic changes
CNS cell death
normal red blood cell cycle
produced in bone marrow
life span 120 days
removed in spleen, liver, bone marrow or blood loss
types of anaemia
microcytic
normocytic
macrocytic
anaemia: mean corpuscular volume
the size of red blood cells, used to determine the type of anaemia
normal: male=81.8-96.3fl, female= 80-98.1fl
microcytic anaemia
small, often hypochromic red blood cells
low MCV
microcytic anaemia: causes
iron deficiency
chronic disease
thalassaemia
microcytic anaemia: iron deficiency
tests= ferritin or iron studies
treat this with iron supplements (ferrous sulphate)
microcytic anaemia: chronic disease
investigate clinically and in a lab
often renal failure or infections
normocytic anaemia
normal MCV but haematocrit and haemoglobin is low
normocytic anaemia: causes
acute blood loss
chronic disease
combined haematinic deficiency (iron, B12, folate)
macrocytic anaemia
red blood cells are larger than normal
bigger MCV
macrocytic anaemia: causes
B12/folate deficiency
alcohol excess/liver disease
hypothyroid
anaemia: B12 deficiency
IF antibodies
schilling test
coeliac antibodies
treat with B12 replacement
haemoglobinopathies
disorders of quality such as sickle cell
disorders of quantity such as thalassaemia
sickle cell disorders
mutated Hb distorts RBCs into crescent shape at low oxygen levels
arise from homozygous state (SS) or combined heterozygous (SC or Sb)
sickle cell pathogenesis
Hb S is a variant Hb arising because of a point mutation in the b globin gene
sickles cell carriers
symptom free
protection against falciparum malaria
managing sickle cell disorders
acute complications such as sickle chest syndrome or stroke
chronic complications such as renal and joint damage
disease modification- transfusion, stem cell transplant
thalassaemia
heterogenous disorders- deletions(alpha thal) and mutations (beta thal)
globin chain disorders resulting in diminished synthesis of 1 or more chains
causes a decrease in Hb
clinical classification of thalassaemia
thal major= transfusion dependent
intermedia= can survive w/o regular transfusions
carrier= asymptomatic
thalassaemia major
age presented is 6-12 months
severe anaemia
1000 sufferers in UK
220,000 carriers in UK
thalassaemia major presentation
failure to feed
listless
crying
pale
thalassaemia major blood results
Hb=40-70g/L
MCV and MCH low
irregular and pale RBCs on film
ferritin normal
treating thalassaemia major
regular transfusions
iron chelation
endocrine supplementation
bone health
monitoring thalassaemia major
ferritin cardiac and liver MRI vit D, calcium PTH thyroid endocrine testing
morbidity and mortality from transfusional iron overload
- thalassaemia results in death during childhood if not treated with transfusions
- transfusions causes increase in body iron load as no natural means for elimination
- excess iron is deposited in the liver and spleen causing fibrosis and cirrhosis
- also deposited on glands and heart= diabetes, heart failure and premature death
membranopathies
deficiency of red cell membrane proteins
autosomal dominant
spherocystosis( vertical interaction) and elliptocytosis (horizontal) are most common
consequences of membranopathies
neonatal jaundice
mild to moderate haemolytic anaemia w/ occasional exacerbations during infection
gallstones
parvovirus and haemolytic anaemias
common infection in children
occurs in epidemics
leads to decreased RBC production
dramatic drop in patients who have reduced red cell lifespan
enzymopathies
lead to shortened red cell lifespan from oxidative damage
G6PD deficiency and pyruvate kinase deficiency are most common
glucose 6 phosphate dehydrogenase deficiency
caused by mutations within G6PD gene
most are asymptomatic
X-linked but females also affected
african, middle eastern, mediterranean and south asian
glucose 6 phosphate dehydrogenase deficiency consequences
haemolysis, jaundice, anaemia
usually self-limiting
symptomatic patients rate
primaquine and glucose 6 phosphate dehydrogenase deficiency
this drug is used for curing malaria but should not be prescribed to someone with g6pdd as it can react to cause haemolytic anaemia
FBC reference ranges
HB=131-166
WBC=3.5-9.5
plts=150-400
MCV= 81.8-96.3
polycythaemia
too many red blood cells
polycythaemia causes
primary cause or proliferative= polycythaemia ruba vera
secondary/reactive= smoking, lung disease, altitude, cyanotic heart disease
polycythaemia ruba vera (PRV)
overactive bone marrow
mainly RBCs but also WBCs and Plts
JAK2 mutation is 95%
polycythaemia ruba vera (PRV) presentation
plethoric appearance
thrombosis
itching
splenomegaly
polycythaemia ruba vera (PRV) treatment
aspirin
venesection
bone marrow suppression drugs
neutrophilia
increase in number of neutrophils
neutrophilia causes
reactive= infection, inflammation, malignancy primary= chronic myeloid leukaemia
neutropenia
abnormally low conc. of neutrophils
neutropenia severity
normal 1.7-6.5
mild 1-1.7
moderate 0.5-1
severe (major infection risk) <0.5
neutropenia caused by underproduction
marrow failure
marrow infiltration
marrow toxicity e.g. drugs
neutropenia caused by increased removal
autoimmune
cyclical
lymphocytosis
increase in number of lymphocytes, neutrophil number normal
lymphocytosis causes
reactive= infection, inflammation, malignancy primary= chronic lymphocytic leukaemia
thrombocytopenia
abnormally low levels of thrombocytes
thrombocytopenia caused by increased destruction
autoimmune
hypersplenism
drug related immune destruction
consumption of platelets
thrombocytopenia caused by decreased production
- congenital
- bone marrow infiltration
- reduced platelet production by bone marrow
- dysfunctional production of platelets
thrombocytosis
excessive number of platelets
thrombocytosis causes
reactive= infection, inflammation, malignancy primary= essential thrombocythaemia
platelet physiology
anucleate cell, fragments from megakaryocytes
regulated by thrombopoietin
platelet tests
number- FBC
appearance- blood film
function- PFA, bleeding time
surface proteins- flow cytometry
causes of bleeding
injury vascular disorders low platelets abnormal platelet function defective coagulation
clinical features of platelet dysfunction
mucosal bleeding gum bleeding easy bruising purpura traumatic haematomas
causes of low platelets
production failure (drugs, marrow suppression or failure, acquired, congenital) increased removal (immune, consumption, splenomegaly)
congenital impaired platelet function
von willebrand disease
platelet disorders
acquired impaired platelet function
uraemia
drugs
immune thrombocytopenia
IgG antibodies formed against platelets and megakaryocyte surface glycoproteins
primary immune thrombocytopenia
may follow viral infection or immunisation
secondary immune thrombocytopenia
occurs in association with some malignancies such as chronic lymphocytic leukaemia
HIV/Hep C infections
immune thrombocytopenia: investigations
for the underlying cause
diagnosis of exclusion
immune thrombocytopenia: treatment
immunosuppression
treat underlying cause
give platelets if bleeding
disseminated intravascular coagulation
blood clots form throughout the body, blocking small blood vessels
disseminated intravascular coagulation: pathophysiology
cytokine release in response to systemic inflammatory response syndrome
activates clotting cascade
disseminated intravascular coagulation: investigations
underlying cause
evidence of organ failure
disseminated intravascular coagulation: treatment
treat underlying cause
supportive provision of platelets, fibrinogen and clotting factors
thrombotic thrombocytopenia purpura
spontaneous platelet aggregation in microvasculature (brain, kidney, heart)
reduction in protease enzyme
thrombotic thrombocytopenia purpura: consequences
consumption of platelets
microangiopathic haemolytic anaemia
renal/CNS/cardiac impairment
thrombotic thrombocytopenia purpura: treatment
plasma exchange immunosuppression no platelets- increases thrombosis 90% mortality 10-20% mortality if treatment starts promptly
neutropenia and neutropenic sepsis
abnormally few neutrophils in the blood leads to increased susceptibility to infection
neutropenic sepsis: causes
decreased production due to problem with the bone marrow
haematologist- chemo
neutropenic sepsis: features
fever
rigor
feeling unwell or off
low BP (not as common)
neutropenic sepsis: when to suspect
if they had chemo in the last 3 months
present with fever
chills/rigor
isolated hypotension
neutropenic sepsis: what to do
see patient
put in cannula
give antibiotics
neutropenic sepsis: early management
first dose of antibiotics is important
if in doubt give them antibiotics
sickle cell crisis: features
- precipitated by dehydration, cold weather and/or infection
- gradual onset over a few days
- then unbearable pain in arms, back, chest or abdo
- poor prognosis if: chest pain, severe abdo pain or neurological symptoms
sickle cell crisis: what to do
see patient
control the pain
put in cannula and start fluids
sickle cell/acute chest syndrome
cycle of hypoxia, sickles and lung infarction
acute chest syndrome: features
new signs on chest xray
hypoxia
acute chest syndrome: what to do
see patient
give oxygen, fluids, antibiotics
call haematologist
spinal cord compression
occurs in any malignancy due to metastases of the spine
particularly prone= myeloma patients
can be caused by plasmacytoma
spinal cord compression: symptoms
back pain neuropathic pain leg weakness saddle anesthesia loss of sphincter control
spinal cord compression: clinical signs
decreased power in legs
typically decreased reflexes
decreased sensitivity
decreased anal tone
spinal cord compression: what to do
keep them in bed
dexamethasone 8mg
urgent MRI
spinal cord compression: treatment
surgical- avoid in myeloma
medical- radiotherapy and chemo
hyperviscosity syndrome
malignant plasma cells produce a lot of immunoglobulin which increases the thickness of your blood
hyperviscosity syndrome: symptoms
non specific symptoms headache neurological blurred vision fatigue mucosal bleeding confusion
hyperviscosity syndrome: examination
general=bruising
CVS= pulmonary oedema, evidence of fluid overload
neuro= confusion, ataxia, nystagmus
hyperviscosity syndrome: what to do
put in cannula
fluids
call haematologist
tumour lysis syndrome
chemo kills cancer cells- making them release intracellular components
this overwhelms the kidneys causing crystallisation and renal failure
tumour lysis syndrome: those at risk
large tumour burden= more cells to die= greater risk
aggressive cancer= rapid cell turnover= greater risk
tumour lysis syndrome: features
blood tests hyperkalaemia= first sign hyperphosphataemia hyperuricaemia hypocalcaemia
tumour lysis syndrome: prevention
- much easier than treatment
- give vigorous IV fluids during chemo and days after
- rasburicase eliminates uric acid
- monitor bloods and urine output closely
tumour lysis syndrome: treatment
fluids rasburicase monitor urine output manage electrolytes dialysis
