haematology Flashcards
features of myeloma
OLD age
Ca elevated
Renal failure
Anaemia (+neuropenia + thrombocytopenia)
Bone lytic lesions
Usually afro-caribbean, 70 yrs, M
what is myeloma
a haematological cancer characterised by proliferation of plasma cells in the bone marrow
Plasma cells produe excess of 1 type of immunoglobulin (IgG) + levels of others are low
myeloma ix
serum protein electrophoreses = monoclonal protein bands (excess of M protein)
-> GS
Bence-Jones protein in urine
Blood film = Rouleaux formations
X-ray = lytic lesions (pepper-pot skull), osteoporosis, fractures
Bone marrow biopsy = excess plasma cells
what is immune thrombocytopenic purpura
a condition where antibodies are created against platelets. An immune response against platelets leads to their destruction and a low platelet count (thrombocytopenia)
Usually IgG antiplatelet autoantibodies
presentation immune thrombocytopenic purpura
Usually an isolated thrombocytopenia found as an incidental finding or w features of pupura/other minor bleeding
may follow infection/vaccination espesh in kids (adults it is more chronic)
PURPURA are non-blanching lesions caused by bleeding under the skin
mx immune thrombocytopenic purpura
monitor platelet count
control BP
suppressing menstrual periods
<30x10^9/L platelet count / >+ features/high risk = ORAL PREDNISOLONE
IV immunoglobulin if active bleeding as works faster
Splenectomy if this doesn’t work
Rituximab (a monoclonal antibody that targets B cells - B cells produce antibodies)
indication for blood transfusion
Hb < 70g/L
or <80 if they have acute coronary syndrome
most common inherited thrombophilia
factor V leiden
increases risk of VTE
Any of the following features in a person aged 0-24 years should prompt a very urgent full blood count (within 48 hours) to investigate for leukaemia:
Pallor
Persistent fatigue
Unexplained fever
Unexplained persistent infections
Generalised lymphadenopathy
Persistent or unexplained bone pain
Unexplained bruising
Unexplained bleeding
young px w hepatosplenomegaly or unexplained petichiae
referred for immediate assessment
what is essential thrombocythaemia
proliferation of megakaryocytes (responsible for production of platelets)
a type of blood cancer
what is primary myelofibrosis
proliferation of hematopoietic stem cells
- normal bone marrow tissue is gradually replaced with a fibrous scar-like material
-> extramedullary haematopoiesis
rare chronic disorder
features of Buerger’s disease (a small and medium vessel vasculitis)
strongly assoc w smoking
extremity ischaemia (as blood vessels become blocked)
- intermittent claudication
- ischaemic ulcers
superficial thrombophlebitis
Raynaud’s phenomenon
what is neutropenic sepsis
overwhelming infection that can affect people who have a low neutrophil count
an emergency
usually comp of chemo 7-14 days after
may be defined as a neutrophil count of < 0.5 * 109 in a patient who is having anticancer treatment and has one of the following:
a temperature higher than 38ºC or
other signs or symptoms consistent with clinically significant sepsis
most common cause of neutropenic sepsis
(a bacteria)
coagulase-negative, Gram-positive bacteria - particularly Staphylococcus epidermidis
probs due to indwelling lines
neutropenic sepsis prophylaxis
a fluoroquinolone
e.g. ciprofloxacin
tx for neutropenic sepsis
empirical antibiotic therapy with piperacillin with tazobactam (Tazocin) immediately
what inheritance pattern is hereditary spherocytosis
autosomal dominant
what is the presentation of Hereditary spherocytosis
- jaundice
- anaemia
- gallstones
- splenomegaly
can have episodes of haemolytic crisis / aplastic crisis
what is aplastic crisis
increased anaemia, haemolysis and jaundice, without the normal response from the bone marrow of creating new RBCs (demonstrated by extra reticulocytes).
In aplastic crisis there is no reticulocyte response
what infection usually causes aplastic crisis
parvovirus B19
lymph node biopsy for Burkitt’s lymphoma
starry sky appearance
infection assoc w Burkett lymphoma
EBV
(HIV, malaria)
infection assoc w diffuse large B-cell lymphoma
hep C virus
infection assoc w T cell lymphoma
Human T cell lymphotropic virus type 1
what is polycythaemia rubra vera
blood cancer that causes bone marrow to make too many RBCs
inheritance of haemophilia A + B
X-linked recessive
- so mostly affects males
more common haemophilia
A
what is haemophilia A caused by
deficiency in factor VIII (8)
what is haemophilia B caused by
deficiency in factor IX (9)
presentation of haemophilia
Most cases present in neonates or early childhood
- intracranial haemorrhage, haematomas and cord bleeding in neonates.
Severe
- spontan bleeding into joints (haemoarthrosis) + muscles
how is haemophilia dx
Diagnosis is based on bleeding scores, coagulation factor assays and genetic testing.
mx of haemophilia
- Infusions of the affected factor (VIII or IX)
- Desmopressin to stimulate the release of von Willebrand Factor
- Antifibrinolytics such as tranexamic acid
what is von willebrand disease (VWD)
most common inherited cause of abnormal bleeding
most AD
deficiency, absence or malfunctioning of a glycoprotein called von Willebrand factor (VWF)
type 1-3 (3 most severe)
presentation of VWD
unusually easy, prolonged or heavy bleeding:
Bleeding gums with brushing
Nose bleeds (epistaxis)
Heavy menstrual bleeding (menorrhagia)
Heavy bleeding during surgical operations
FHx
mx of VWD
- tranexamic acid for mild bleeding
- Desmopressin can be used to stimulates the release of VWF
- VWF can be infused
- Factor VIII is often infused along with plasma-derived VWF
what is Richter’s transformation
occurs when leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin’s lymphoma
sx in Richter’s transformation
px get unwell suddenly
lymph node swelling
fever without infection
weight loss
night sweats
nausea
abdominal pain
suspect when you get new B sx in CLL
what is ALL
malignancy of immature lymphoid cells - B + T cells
who gets ALL
2-4 yrs
assoc w Down’s
what is the most common childhood cancer
ALL
ix in ALL
blood film = blast cells
bone marrow biopsy = >20% blast cells
what is AML
uncontrolled proliferation of myeloid blast cells (myeloblasts)
who gets AML
commonest acute leukaemia in adults
65+
can be a result of transformation from myeloproliferative disorder
characteristics of AML
neutropenia and thrombocytopenia
more acute presentation
how does leukaemia normally present
fatigue
fever
bone marrow failure - anaemia -> pallor, decreased WCC -> infection, decreased platelets -> bleeding + bruising (petechiae)
infiltration -> bone pain
hepatosplenomegaly
lymphadenopathy
what do the blast cells have in AML
Auer rods
what is CML
uncontrolled proliferation of myeloid (mature) cells
CML presentation
anaemia
weight loss and sweating are common
splenomegaly may be marked → abdo discomfort, fullness
an increase in GRANULOCYTES AT DIFFERENT STAGES IN MATURATION
+/- thrombocytosis
decreased leukocyte ALP
slow + steady decline
who gets CML
65+
philadelphia chromosome (t(9;22)) present in > 80%
phases of CML
chronic phase - long + asx (raised WCC)
accelerated phase - abnormal blast cells take up a high prop of cells, dev anaemia + thrombocytopenia, immunocomp
blast phase - higher prop, severe sx, pancytopenia
CML tx
IMATINIB is first-line treatment
- inhibitor of the tyrosine kinase
what is CLL
accumulation of mature B lymphocytes in peripheral blood
who gets CLL
most common leukaemia
M
Elderly - 72 yrs
1/3 never progress, 1/3 progress slowly, 1/3 progress actively
ix for CLL
blood film = smudge cells
what is CLL assoc w
warm AI haemolytic anaemia
Richters transformation
electrolyte disturbances in tumour lysis syndrome
hyperkalaemia
hyperuricaemia
hyperphosphataemia
hypocalcaemia
G6PD deficiency inheritance
X-linked recessive
features G6PD deficiency
neonatal jaundice is often seen
intravascular haemolysis
gallstones are common
splenomegaly may be present
G6PD deficiency blood film
Heinz bodies on blood films. Bite and blister cells may also be seen
what can precipitate G6PD deficiency crisis
anti-malarials: primaquine
ciprofloxacin
sulph- group drugs: sulphonamides,
sulphasalazine, sulfonylureas
broad (fava) beans
infection
what is G6PD deficiency
reduced ability of the red cells to respond to oxidative stress -> red cells have a shorter life span + are more susceptible to haemolysis, particularly in response to drugs (e.g. nitrofurantoin), infection, acidosis and certain dietary agents (e.g. fava beans)
reversal for rivaroxaban and apixaban
andexanet alfa
reversal for heparin
protamine sulfate
what is thrombotic thrombocytopenic purpura (TTP)
a condition where tiny thrombi develop throughout the small vessels (microangiopathy), using up platelets
what does thrombotic thrombocytopenic purpura (TTP) cause
Thrombocytopenia
Purpura
Tissue ischaemia and end-organ damage
why do thrombi develop in thrombotic thrombocytopenic purpura (TTP)
problem with a specific protein called ADAMTS13
This protein normally:
- Inactivates von Willebrand factor
- Reduces platelet adhesion to vessel walls
- Reduces clot formation
Deficiency can be due to:
- An inherited genetic mutation
- Autoimmune disease
tx for thrombotic thrombocytopenic purpura (TTP)
guided by a haematologist and may involve plasma exchange, steroids and rituximab
what is heparin-induced thrombocytopenia (HIT)
the development of antibodies against platelets in response to heparin (usually unfractionated heparin, but it can occur with low-molecular-weight heparin)
what do heparin induced antibodies target
platelet factor 4 (PF4).
presentation of heparin-induced thrombocytopenia (HIT)
typically presents around 5-10 days after starting treatment with heparin
HIT antibodies bind to platelets and activate the clotting system, causing a hypercoagulable state and thrombosis. They also break down platelets and cause thrombocytopenia
-> there is a counterintuitive situation where a patient is on heparin, has a low platelet count, and develops abnormal blood clots.
mx of heparin-induced thrombocytopenia (HIT)
testing for HIT antibodies on a blood sample.
Stopping heparin and using an alternative anticoagulant guided by a specialist (e.g., fondaparinux or argatroban).
RFs Hodgkin’s lymphoma
HIV
Epstein-Barr virus
Autoimmune conditions, such as RA and sarcoidosis
Family history
ages who get Hodgkin’s lymphoma
bimodal age distribution with peaks around 20-25 and 80 years.
types of non-Hodgkin’s lymphoma
Diffuse large B cell lymphoma - typically presents as a rapidly growing painless mass in older patients
Burkitt lymphoma - particularly associated with Epstein-Barr virus and HIV
MALT lymphoma - affects the mucosa-associated lymphoid tissue, usually around the stomach
RFs for non-Hodgkin’s lymphoma
HIV
Epstein-Barr virus
Helicobacter pylori (H. pylori) infection is associated with MALT lymphoma
Hepatitis B or C infection
Exposure to pesticides
Exposure to trichloroethylene (a chemical with a variety of industrial uses)
Family history
lymphoma presentation
Lymphadenopathy - neck, axilla or inguinal region, non-tender, firm/rubbery
HODGKINS - lymph node pain after drinking alcohol
B sx - Fever
Weight loss
Night sweats
additional no specific sx
ix lymphoma
Lymph node biopsy
CT, MRI, PET to help dx + stage
characteristic finding Hodgkin’s lymphoma
Reed-Sternberg cells - large cancerous B lymphocytes with two nuclei and prominent nucleoli, giving them a cartoonish appearance of an owl face with large eyes.
classification of lymphoma
Lugano Classification
Stage 1: Confined to one node or group of nodes
Stage 2: In more than one group of nodes but on the same side of the diaphragm (either above or below)
Stage 3: Affects lymph nodes both above and below the diaphragm
Stage 4: Widespread involvement, including non-lymphatic organs, such as the lungs or liver
a / b ? (b has systemic sx)
blood film in myelofibrosis
Teardrop-shaped red blood cells
Anisocytosis (varying sizes of red blood cells)
Blasts (immature red and white cells)
blood finding in polycythaemia vera
High haemoglobin
blood finding in essential thrombocythaemia
High platelet count
what gene mutation are the myeloproliferative disorders assoc w
JAK2
myelofibrosis presentation
non-specific symptoms: Fatigue
Weight loss
Night sweats
Fever
underlying comps: Anaemia (tiredness, SOB and dizziness)
Splenomegaly (abdominal pain)
Portal hypertension (ascites, varices and abdominal pain)
Low platelets (bleeding and petechiae)
Raised haemoglobin (itching, headaches and a red face)
Low white blood cells (infections)
Gout is a complication of polycythaemia
Thrombosis
Clinical signs of polycythaemia
Ruddy complexion (red face)
Conjunctival plethora (the opposite of conjunctival pallor)
Splenomegaly
Hypertension
dx myelofibrosis
Bone marrow biopsy to confirm dx
the aspiration may be dry as it has turned to scar tissue
Testing for the JAK2, MPL and CALR genes
mx primary myelofibrosis
no active tx if mild
supp mx comps e.g. anaemia, splenomegaly, portal HTN
chemo - hydroxycarbamide
targeted therapies, such as JAK2 inhibitors (ruxolitinib)
mx polycythaemia vera
venesection
aspirin to reduce the risk of thrombus formation
Chemotherapy - hydroxycarbamide
mx essential thrombocythaemia
aspirin to reduce the risk of thrombus formation
Chemotherapy - hydroxycarbamide
Anagrelide is a specialist platelet-lowering agent
what is sickle cell anaemia
genetic condition that causes sickle (crescent) shaped RBCs
- more fragile + easily destroyed -> haemolytic anaemia.
prone to various sickle cell crises.
inheritance sickle cell
AR
- affecting the gene for beta-globin on chromosome 11
sickle cell + malaria
sickle cell is more common in patients from areas traditionally affected by malaria, such as Africa, India, the Middle East and the Caribbean
Having sickle cell trait reduces the severity of malaria so these px are more likely to survive malaria and pass on their genes.
ie there is a selective adv to having the sickle cell gene
complications of sickle cell
Anaemia
Increased risk of infection
Chronic kidney disease
Sickle cell crises
Acute chest syndrome
Stroke
Avascular necrosis in large joints such as the hip
Pulmonary hypertension
Gallstones
Priapism (painful and persistent penile erections)
what is sickle cell crisis triggered by
dehydration, infection, stress or cold weather.
tx sickle cell crisis
Low threshold for admission to hospital
Treating infections that may have triggered the crisis
Keep warm
Good hydration (IV fluids may be required)
Analgesia (NSAIDs should be avoided where there is renal impairment)
what is vaso-occlusive Crisis
most common crisis
also called painful crisis
sickle-shaped red blood cells clog capillaries -> distal ischaemia
Vaso-occlusive Crisis presentation
pain and swelling in the hands or feet but can affect the chest, back, or other body areas. It can be associated with fever.
can cause priapism in men by trapping blood in the penis, causing a painful and persistent erection (uro emergency and needs blood to be aspirated from the penis)
what is splenic sequestration crisis
emergency caused by sickled RBCs blocking BF within the spleen
-> acutely enlarged and painful spleen. Blood pooling in the spleen can lead to severe anaemia and hypovolaemic shock.
mx aplastic crisis
supportive - may need blood transfusions
usually resolves spontaneously within around a week
what is acute chest syndrome
occurs when the vessels supplying the lungs become clogged with RBCs
med emergency w high mortality
what can trigger acute chest syndrome
A vaso-occlusive crisis, fat embolism or infection
presentation acute chest syndrome
fever
SOB
chest pain
cough
hypoxia
CXR acute chest syndrome
pulmonary infiltrates
mx sickle cell disease
Avoid triggers for crises, such as dehydration, smoking, alcohol, cold, exhaustion
Up-to-date vaccinations
Antibiotic prophylaxis (3 MTHS - 5 YRS) to protect against infection, typically with penicillin V
(phenoxymethylpenicillin)
Hydroxycarbamide (/HYDROXYUREA) (stimulates HbF)
- reduces the frequency of painful episodes and the risk of life-threatening illness or death
1 mg of folic acid orally every day
Crizanlizumab
Blood transfusions for severe anaemia
Bone marrow transplant can be curative
what is myelodysplastic syndrome
cancer caused by mutation in the myeloid cells in the bone marrow -> inadequate production blood cells (ineffective haematopoiesis)
various types
had potential to dev into AML
bloods in myelodysplastic syndrome
causes low levels of blood components that originate from the myeloid cell line:
Anaemia (low haemoglobin)
Neutropenia (low neutrophil count)
Thrombocytopenia (low platelets)
-> PANCOCYTOPENIA
Dx myelodysplastic syndrome
Full blood count will be abnormal. There may be blasts on the blood film.
Bone marrow biopsy is required to confirm the diagnosis.
causes of microcytic anaemia
T – Thalassaemia
A – Anaemia of chronic disease
I – Iron deficiency anaemia
L – Lead poisoning
S – Sideroblastic anaemia
when can you commonly get anaemia of chronic disease + why
in CKD
due to reduced production of erythropoietin by the kidneys
tx w erythropoietin
causes of normocytic anaemia
3 As 2 Hs
A – Acute blood loss
A – Anaemia of chronic disease
A – Aplastic anaemia
H – Haemolytic anaemia
H – Hypothyroidism
types of macrocytic anaemia
megaloblastic - as a result of impaired DNA synthesis, instead of dividing they grow into large, abnormal cells
normoblastic
causes of megaloblastic macrocytic anaemia
B12 deficiency
Folate deficiency
causes of normoblastic macrocytic anaemia
Alcohol
Reticulocytosis (usually from haemolytic anaemia or blood loss)
Hypothyroidism
Liver disease
Drugs, such as azathioprine
signs that point to iron deficiency anaemia
Koilonychia - spoon-shaped nails
Angular cheilitis
Atrophic glossitis - smooth tongue due to atrophy of papillae
Brittle hair + nails
causes of low B12
Pernicious anaemia - AI condition
Insufficient dietary B12 (particularly a vegan diet, as B12 is mostly found in animal products)
Medications that reduce B12 absorption (e.g., PPIs and metformin)
what is pernicious anaemia
autoimmune condition involving antibodies against the parietal cells or intrinsic factor
parietal cells of the stomach produce intrinsic factor protein which is essential for the absorption of vitamin B12 in the distal ileum
-> there is lack of B12
sx of B12 deficiency
neurological:
Peripheral neuropathy, with numbness or paraesthesia
Loss of vibration sense
Loss of proprioception
Visual changes
Mood and cognitive changes
autoantibodies for pernicious anaemia
Intrinsic factor antibodies (the first-line investigation)
Gastric parietal cell antibodies (less helpful)
mx pernicious anaemia
IM hydroxocobalamin (manufactured version of B12)
- if no neuro sx give 3x weekly for 2 weeks
- if neuro sx give pn alt days until there is no further improvement in sx
maintenance mx in B12 deficiency
Pernicious anaemia – 2-3 monthly injections hydroxocobalamin for life
Diet-related – oral cyanocobalamin or twice-yearly injections
what to do when a px has both B12 + folate deficiency
treat B12 deficiency 1st
if you give px folic acid when they have B12 deficiency -> subacute combined degeneration of the cord
what does normal haemoglobin consist of
two alpha-globin and two beta-globin chains
inheritance of thalassaemia
AR
(both alpha + beta)
what happens to RBCs in thalassaemia
they are more fragile + break down easily -> haemolytic anaemia
-> splenomegaly
what is thalassaemia
caused by a genetic defect in the protein chains that make up haemoglobin.
Defects in alpha-globin chains lead to alpha thalassaemia. Defects in the beta-globin chains lead to beta thalassaemia
beta thalassaemia minor
also called thalassaemia trait,
carriers of an abnormally func beta-globin gene
- mild microcytic anaemia - microcytosis is characteristically disproportionate to the anaemia
- HbA2 raised (> 3.5%)
usually asx
just needs monitoring
beta thalassaemia intermedia
two abnormal copies of the beta-globin gene. This can be either:
Two defective genes
One defective gene and one deletion gene
more signif microcytic anaemia
monitoring, might need occasional blood transfusions, may need iron chelation to prevent iron overload
beta thalassaemia major
homozygous for the deletion genes. They have no functioning beta-globin genes.
severe anaemia + failure to thrive in early childhood
bone marrow under strain to produce extra RBCs -> expands increasing fracture risk + changing px appearance
mx = regular transfusions, iron chelation and splenectomy. A bone marrow transplant can be curative.
common comp in thalassaemia
iron overload due to
Increased iron absorption in the gastrointestinal tract
Blood transfusions
monitor serum ferritin
what vaccine should sickle cell px have + how often
the pneumococcal polysaccharide vaccine every 5 years
phosphate levels in myeloma
high as reduced renal excretion
indications for exchange transfusion in sickle cell disease
acute vaso-occlusive crisis, stroke, acute chest syndrome, multiorgan failure, splenic sequestration crisis
in individuals with a ‘high’ haemoglobin (>90g/L), where a blood transfusion could worsen the outcome by increasing serum viscosity and clogging the vessels more
it rapidly reduces the percentage of Hb S containing cells
indications for blood transfusion in sickle cell disease
severe or symptomatic anaemia, pregnancy, pre-operative
does not rapidly reduce the percentage of Hb S containing cells
what is a non-haemolytic febrile reaction
to blood transfusion
due to white blood cell HLA antibodies
often the result of sensitization by previous pregnancies or transfusions
paracetamol may be given
commonly presents with fever, rigors, and general discomfort
what is an acute haemolytic transfusion reaction
results from a mismatch of blood group (ABO) which causes massive intravascular haemolysis. This is usually the result of red blood cell destruction by IgM-type antibodies.
presentation acute haemolytic transfusion reaction
Symptoms begin minutes after the transfusion is started and include a fever, abdominal and chest pain, agitation and hypotension.
what is transfusion-related acute lung injury (TRALI) + features
Rare but potentially fatal complication of blood transfusion.
Characterised by the development of hypoxaemia / acute respiratory distress syndrome within 6 hours of transfusion.
Features include:
hypoxia
pulmonary infiltrates on chest x-ray
fever
hypotension
what is transfusion-associated circulatory overload (TACO)
+what is a key thing to differentiate it from TRALI
A relatively common reaction due to fluid overload resulting in pulmonary oedema. As well as features of pulmonary oedema the patient may also by HYPERTENSIVE (a key difference from patients with TRALI)
blood film in hyposplenism (in coeliac, or post-splenectomy)
target cells
Howell-Jolly bodies
Pappenheimer bodies
siderotic granules
acanthocytes
what is raised + reduced in beta thalassaemia major
HbA2 & HbF raised
HbA absent
signs of poor prognosis in hodgkin’s lymphoma
lymphopenia
leukocytosis
raised ESR
raised LDH
decrease in albumin
features of lead poisoning
Abdominal pain, constipation, neuropsychiatric features, basophilic stippling
blue lines on gums (Burton’s line)
what type of blood products to give in immunosuppressed + why
Irradiated blood products are used to avoid transfusion-associated graft versus host disease
2ndary causes of thrombocytosis
bleeding
inflammation
cancer
types of AI haemolytic anaemia + which is most common
warm type - most common
cold type
causes of warm AIHA
idiopathic
autoimmune disease: e.g. SLE
lymphoma
chronic lymphocytic leukaemia
drugs: e.g. methyldopa
tx warm AIHA
treatment of any underlying disorder
steroids (+/- rituximab) are generally used first-line
potential cure for thalassaemia
bone marrow transplant
dx test for thalassaemia
haemoglobin electrophoresis
tx non-hodgkin’s lymphoma
Rituximab in combo w conventional chemotherapy regimes
cancer likely to cause tumour lysis syndrome
burkitt’s lymphoma
reversal agent for DAbigatran
iDArucizumab
