haematology Flashcards
what are the two types of haemachromatosis
Primary Haemochromatosis
→ hereditary, most common form
Autosomal recessive inheritance
Mutations on the HFE gene
Secondary Haemochromatosis
→ caused by iron overload
Commonly transfusion related
which gene causes primary haemachromatosis and what is the inheritance pattern
HFE gene
Autosomal recessive
symptoms of haemachromatosis
fatigue
arthralgia
erectile dysfunction
grey/bronze pigmentation
polyuria / polydipsia
cirrhosis / hepatomegaly
what is the most useful marker for haemachromatosis
serum transferrin saturation >45%
what is the first test to become abnormal in haemachromatosis
serum transferrin saturation >45%
describe the iron study results for haemachromatosis
high serum iron
high serum ferritin
low TIBC
serum transferrin saturation >45%
management of haemachromatosis
1st line: therapeutic phlebotomy
2nd line: drug induced iron chelation - Deferoxamine
what globins make up HbF
2 alpha globin + 2 gamma globin
what globins make up HbA
2 alpha globin + 2 beta globin
what globins make up HbA2
2 alpha globin + 2 delta globin
what is the inheritance pattern of all haemaglobinopathies (sickle cell, thalassemia)
autosomal recessive
contrast alpha and beta thalassemia in terms of common pt population, number of alleles, and electrophoresis results
beta
- mediterranean descent
- 2 alleles
- no HbA, raised HbA2 and HbF
- no HbH
(look for raised HbA2 in Hb electrophoresis)
alpha
- asian and African descent
- 4 alleles
- present HbH
(look for HbH band in Hb electrophoresis)
what are the 2 forms of beta thalassemia and their symptoms
1 defective allele: Beta thalassemia minor
→ mild microcytic hypochromic anaemia.
Asymptomatic
2 defective alleles: Beta thalassemia major
→ severe haemolytic anaemia,
hepatosplenomegaly,
skeletal deformities
what are the 4 forms of alpha thalassemia and their symptoms
1 defective allele: Silent Carrier
→ asymptomatic.
No anaemia.
2 defective alleles: Αlpha Thalassaemia Trait
→ microcytic hypochromic red cells.
No anaemia.
3 defective alleles: Haemoglobin H (HbH) Disease
→ microcytic hypochromic anaemia with splenomegaly
4 defective alleles: Haemoglobin Bart Disease
→ intrauterine death
management of thalassemia major
lifelong blood transfusion therapy
(this may lead to iron overload so also give iron chelation therapy - Desferrioxamine)
genetic screening
individuals with an absent or dysfunctional spleen are at increased risk of severe infection esp caused by which bacteria?
the encapsulated bacteria - NHS
N. meningitidis
H. influenzae type b (Hib)
S. pneumoniae (pneumococcus)
what is seen on a blood film in hyposplenism / after splenectomy
howell-jolly bodies,
target cells,
pappenheimer bodies (siderocytes)
what do Howell jolly bodies indicate
splenic dysfunction
why is prophylactic aspirin usually indicted after a splenectomy
pt will have very high platelet count - thrombocytosis
(spleen is the primary site of destruction of platelets)
management of hypospelnism or splenectomy
prophylactic aspirin if they have thrombocytosis
Immunisations
→ vaccinations against
N. meningitidis,
H. influenzae type b and influenza virus
S. pneumoniae,
○ Pneumococcal vaccine 2 weeks before elective splenectomy
○ Annual influenza vaccination and Pneumococcal vaccine every 5 years
Prophylactic Antibiotics (Penicillin or Amoxicillin)
→ recommended in patients at high risk of pneumococcal infections
causes of DIC
STOP MT
⇒ sepsis/snakebites,
trauma,
osbtetric conditions,
pancreatitis,
malignancy,
Transfusion
acute vs chronic DIC
acute
- caused by trauma, sepsis and blood transfusions
- causes bleeding issues (petechiae, purpura, ecchymoses, epistaxis)
chronic
- caused by malignancy
- causes clotting issues (signs of DVT or arterial thrombosis)
significant FBC results in DIC
low platelets,
low haemoglobin
clotting results in DIC
low fibrinogen,
high D-dimer (fibrinogen degradation products),
prolonged PT + APTT
what is seen on blood film in DIC
schistocytes (fragmented RBC)
management of DIC
Platelet + Coagulation Factors Transfusion
○ Fresh Frozen Plasma
→ contains clotting factors (AB = universal donor)
○ Cryoprecipitate
→ replaces fibrinogen
Anticoagulation
→ Heparin
inheritance pattern of sickle cell
autosomal recessive
describe the mutation in sickle cell
mutation on 6th amino acid of beta chain of haemoglobin
polar glutamic acid is replaced by non polar valine
at what age does sickle cell present and why
6 months
HbF decreases and HbS increases
what disease does sickle cell have a protective factor against
malaria
what is the haemaglobin in sickle cell trait vs disease
HbAS - trait
HbSS - disease
describe the 4 dangerous events in sickle cell
vaso-occlusive crisis
- blood vessels blocked by sickle cells causing infarction
ACS (acute chest syndrome)
- pulmonary infiltrates causing dysnpea, wheeze, cough, temp, pain
sequestration crisis (splenic sequestration)
- sickled RBCs sequester in spleen and undergo phagocytosis –> functional hyposplenism –> reduced immune function (esp to encapsulated organisms - NHS)
- HIGH RETICULOCYTES + SPLENOMEGALY
Aplastic crisis
- parvovirus B19 stops erythropoiesis
- LOW RETICULOCYTES + SUDDEN ANAEMIA (drop in Hb)
list some symptoms of sickle cell
vaso-occlusive crisis
dactylitis
bone pain
high temp
Acute chest syndrome
lethargy + anaemia symptoms
splenic sequestration / splenomegaly
what is sickling in sickle cell disease precipitated by
infection
dehydration
hypoxia
acidosis
stress
cold
fatigue
gold standard Ix for sickle cell and results
Hb electrophoresis
- no HbA
- ^ HbF
- present HbS
what does blood film show in sickle cell
sickle cells
Howell jolly bodies
target cells
how does reticulocyte level differ in sequestration crisis vs aplastic crisis
splenic sequestration = high reticulocytes
(as RBCs are being phagocytoses in spleen, so new ones are made more rapidly)
aplastic crisis = low reticulocytes
(as parvovirus B19 stops erythropoiesis)
management of vase-occlusive crisis
strong analgesia
oxygen
fluids
transfusion
abx if infected
tx for chronic sickle cell disease
hydroxyurea (increases HbF which decreased frequency and duration of crisis)
regular transfusion
vaccinations
which mutation is associated with myeloproliferative disorders eg myelofibrosis, polycythaemia vera, thrombocythaemia
JAK2 mutation
describe mechanism of essential thrombocytosis (aka primary thrombocythaemia)
dysregulation of megakaryocyte proliferation
–> increase in circulating platelets
–> thrombocytosis
describe the mechanism of meylofibrosis
fibrosis of bone marrow
–> bone marrow failure
–> myeloproliferation in the spleen (to compensate for bone marrow not making any cells)
–> splenomegaly
which 2 myeloprolifertaive disorders cause massive splenomegaly
myelofibrosis
CML
what is dry tap and what condition is it seen in
failure of bone marrow aspirate
myelofibrosis
what is seen on blood film in myelofibrosis
tear drop poikilocytes (dactrocytes)
–> flat, elongated RBCs
what is erythromelalgia and which conditions is it seen in
warm, red, painful extremities (esp legs/feet)
worse in heat, better in cold
meyloprolifertaive disorders, some autoimmune diseases (eg lupus, MS)
what is the platelet count in myeloproliferative disorders
≥450 x 10⁹/L
which medication can be used to reduce platelet count in myeloroliferative disorders
hydroxycarbamide
(and use aspirin to precent thrombosis)
what is the inheritance pattern if haemophilia
X linked recessive
(so only in males)
what stage of haemostasis is affected in haemophilia
secondary haemostasis - as haemophilia causes a deficiency of coagulation factor
which factors are deficient in haemophilia A vs B
A –> 8
B —> 9
is haemophilia A vs B more common
A
how do you classify haemophilia severity according to haematoma formation
mild - haematoma formation after severe trauma
moderate - haematoma formation after mild trauma
severe - spontaneous haematoma formation
what is the hallmark sign/symptom of haemophilia
MSK bleeding
(pain/swelling/erythema/warmth.reduced rang of motion)
describe the investigations needed for haemophilia
test homeostasis pathways: prolonged APPT, normal PT
do a plasma factor 8 and 9 assay to confirm diagnosis
can also d a mixing study
what is the resist of a mixing study in haemophilia
correction of APTT with the mixing study suggests a coagulation factor deficiency and hence haemophilia
which medication can be used to increase factor 8 in haemophilia A and how
Desmopressin
- triggers release of VWF which increases factor 8
which medications can inhibit break down clots and reduce risk bleeding in haemophilia
tranexamic acid
aminocarporic acid
what is the most common inherited bleeding disorder
Von willebrand disease
contrast type 1,2,3 von willebrand disease in terns of effect on VWF and inheritance pattern
Type 1
→ partial reduction in vWF
(autosomal dominant)
Type 2
→ abnormal form of vWF
(autosomal dominant)
Type 3
→ total lack of vWF
(autosomal recessive)
which condition does this describe
prolongued bleeding time, prolonged APTT, factor 8 levels may be reduced
von willebrand disease
describe bleeding time in haemophilia
normal, APTT is prolonged
normal bleeding time, prolonged APTT, no factor 8
what condition does this describe
haemophilia A
normal bleeding time, prolonged APTT, no factor 9
what condition does this describe
haemophilia B
Tx for Von willebrand disease
tranexamic acid for mild bleeding,
desmopressin,
factor 8 concentrate
which medication can cause bone marrow suppression and hence pancytopenia
methotrexate
what type of anaemia is aplastic anaemia
normochromic normocytic anaemia
investigations for pancytopenia
FBC and blood smear
Then,
- bone marrow biopsy to check if bone marrow suppression is the cause
- LFTs / B12 and folate / coagulation / viral serology / autoimmune profile
- screen for PNH and IBMFS
(PNH = paroxysmal nocturnal haemoglobinuria, IBMFS = inherited bone marrow failure syndrome)
pancytopenia tx
RBC and platelet transfusion
bone marrow / stem cell transplant
what is polycythaemia
increase in Hb conc
what is relative vs absolute (true) polycythaemia
○ Relative Polycythaemia
⇒ normal red cell mass but low plasma volume
-Relative Causes
→ dehydration, stress
Absolute (True) Polycythaemia
⇒ increased red cell mass
- causes hyper-viscosity (mucosal bleeding, neurological symptoms, visual changes, thrombosis)
what is hyperviscocity syndrome and which type of polycythaemia does it present in
presents in absolute/true polycythaemia which is when there’s an increased red cell mass
triad of:
mucosal bleeding
neurological symptoms (headache, dizzy)
visual changes
and increases risk of thrombosis
what is primary vs secondary polycythaemia
primary (aka Polycythaemia Vera)
- EPO independent
therefore EPO is LOW
- can be caused by Budd-Chiari syndrome
- can cause acute myeloid leukaemia or myelofibrosis
secondary
- EPO dependent (driven by excess EPO
therefore EPO is high
- due to either
chronic hypoxia (COPD, living at high altitude)
or inappropriate increase in EPO (hepatocellular/renal carcinoma, EPO abuse by athletes)
which mutation do you look for if you suspect polycythaemia vera
positive JAK 2 gene mutation
symptoms of polycythaemia
red face
painful burning and redness of hands/feet
pruritus - WORSE in WARM water
splenomegaly
hyoerviscosity syndrome (mucosal bleeding, neurological symptoms, visual changes )
what are Hb, haematocrit and platelet levels in polycythaemia
all elevated
management/tx for polycythaemia
phlebotomy (venesection)
aspirin
cryoreductive therapy
JAK2 inhibitor (ruxolitinib) for polycythaemia vera
what condition increases risk of both acute leukemias
down syndrome
what is the most common leukaemia in children
Acute lymphoblastic leukaemia
what age is acute myeloid leukaemia seen in
adults, 65 yrs
what is the most common cause of AML
pre-existing haematopoietic disorders eg aplastic anaemia, myeloprolifertaive disorders
what is seen on cytology in AML
Auer rods ( large pink/red stained needle-like structures)
what are the distinguishing signs/symtpoms between ALL and AML
ALL - has lymphadenopathy and fevers
AML - does NOT have lymphadenopathy and fevers
describe the levels of cells in acute leukaemia
everything low - neutropenia, thrombocytopenia, anaemia
EXCEPT blasts which are high
what is present on peripheral blood smear in acute leukaemia
presence of blast cells (immature WBCs)
how to confirm diagnosis of acute leukaemia
Bone Marrow Aspiration & Biopsy
→ Hypercellular marrow with >20% of cells being lymphoblasts (ALL).
what is the most common type of leukaemia in adults
CLL (chronic lymphocytic leukemia)
what is Richter transformation and what are signs of it
when chronic lymphocytic leukaemia transforms to become non hodgkins lymphoma
(presents with lymph node swelling, fever, weight loss, night sweats)
the proliferation of which cells causes chronic lymphocytic leukaemia
B cells (lymphocytes)
what is seen on blood film in chronic lymphocytic leukaemia
smudge ie smear cells
thromobotic risk level in all the different types of leukaemia
acute: low thrombotic risk (thrombocytopenia)
CLL: low thrombotic risk (thrombocytopenia)
CML: hyper-viscosity so higher thrombotic risk
the proliferation of which cells causes chronic myeloid leukaemia
granulocyte
in which type of leukaemia is there an increase in all the cells whilst the others dont
CML
which gene mutation is associated with CML
philadelphia chromosome
reciprocal translocation between chromosome 9 and chromosome 22.
The resulting BCR-ABL gene codes for a fusion protein that has tyrosine kinase activity in excess of norma
levels of leukocyte alkaline phosphatase (LAP) in CML
low
which medication can be used in tx of CML
tyrosine kinase inhibitor (Imatinib)
what is the urgent referral criteria for leukaemia in 0-24 yr olds
refer for immediate specialist assessment for leukaemia if unexplained petechiae or hepatosplenomegaly (urgent FBC)
mx of leukemia
chemotherapy
radiotherapy
stem cell transplant
what is seen on blood film in ALL
blast lymphoid cells
what is seen on blood film in CML
left shift
which type of leukaemia presents with massive splenomegaly
CML (think, the one that has the higher levels of cells)
contrast hogdkin and non Hodgkins lymphoma
hodgkin
- B cells
- bimodal age distribution
- due to EBV, or immunosuppression (eg HIV)
- affects lymph nodes above diaphragm
- contiguous spread, only affects a single group of nodes
- extra nodal involvement is rare
- B symptoms are early, and are also a sign of bad prognosis
- Reed Sternberg cells
- better prognosis, less common
non hodgkin
- B or T cells
- increases with age
- due to chromosomal translocation, infection, autoimmune conditions, immunodeficiency
- affects multiple node groups
- non contiguous spread
- extra nodal involvement is common
- neoplastic cells of B cell lineage
- B symptoms are later
- worse prognosis, more common
what type of lymphoma are Reed Sternberg cells associated with
hodgkin lymphoma (particularly, mixed cellular hodgkin lymphoma)
what are the 4 types of hodgkin lymphomas
nodular sclerosing
- most common
- good prognosis
- females
- lacunar cells
mixed cellularity
- good prognosis
- many Reed Sternberg cells
lymphocyte predominant
- best prognosis
lymphocyte depleted
- rare
- worst prognosis
symptoms of hodgkin lymphoma
painless lymphadenopathy most commonly involving the cervical or supraclavicular nodes.
Involvement of single group of lymph nodes.
Alcohol induced pain.
Pruritus.
B symptoms.
symptoms of non hodgkin lymphoma
rubbery painless lymphadenopathy associated with fatigue.
Splenomegaly.
Extranodal disease = GI (dyspepsia, dysphagia, abdo pain), bone marrow (bone pain), neurological (headache).
Affects multiple nodes
which type of lymphoma has a starry sky appearance on microscopy
burkitt’s lymphoma (subtype of non hodgkin lymphoma)
what patients is a burkitt’s lymphoma common in
HIV pts
what can happen as a result of a burkitt’s lymphoma’s response to chemotherapy
Chemotherapy tends to produce rapid response which can cause tumour lysis syndrome
Tumour Lysis Syndrome → PUKE Calcium = phosphorus, uric acid, potassium elevated. Calcium reduced.
Ix for hogdkin vs non Hodgkins lymphoma
hodgkin
- histology and biopsy
(reed Sternberg cells)
non hodgkin
- lymph node biopsy and immunohistochemistry
what does elevated LDH mean for lymphomas
poor prognosis
what imaging modality and scoring system is used for staging lymphomas
PET-CT CAP → staging (“lugano classification” based on the Ann-Arbor Staging)
Stage 1 - One node affected
Stage 2 - More than one node affected on the same side of the diaphragm
Stage 3 - Nodes affected on both sides of the diaphragm
Stage 4 - Extra-nodal involvement e.g. Spleen, bone marrow or CNS
tx for lymphomas
chemo and/or radiotherapy
what are some factors which suggest worse prognosis for hodgkins lymphoma
B-symptoms,
increasing age (>45),
male,
stage 4 disease
lymphocyte depleted subtype.
what are the most common oral anticoagulants
vitamin K antagonists (warfarin) and DOACs (apixaban)
what is the most common parenteral anticoagulant
heparin
which factors is vitamin K responsible for the production of
2, 7, 9, 10
what is the mechanism of warfarin
vit K antagonist
what are the advantages and disadvantages of warfarin
+
can be directly reversed by replacement of warfarin
- long half life
lots of interactions
requires regular monitoring via INR and PT
target INR for metallic mitral valve replacement
2.5-3.5 (3)
target INR for AF
2 - 3 (2.5)
target INR for metallic aortic valve replacement
2 - 3 (2.5)
target INR following VTE
2 - 3 (2.5)
what type of med are apixaban / rivoroxaban and what is their mechanism
DOAC
factor 10a inhibitors
why are DOACs preferred to warfarin
they require less monitoring
what type of med is enoxaparin
LMWH
contrast unfractioned (standard) heparin and LMWH (enoxaparin)
and which is preferred and why
Unfractionated (Standard) Heparin
→ IV, short acting, monitored via APTT
LMWH (eg. enoxaparin)
→ subcutaneous, long acting, monitored via anti-factor 10a.
Usually preferred as lower risk of heparin-induced thrombocytopenia.
(Activates antithrombin III. Forms a complex that inhibits factor 10a)
site of action of heparin vs warfarin
heparin - blood
warfarin - liver
monitoring of heparin vs warfarin
heparin
- APTT (standard)
- antifactor 10a (LMWH)
warfarin
- INR
- PT
routes of administration heparin vs warfarin
heparin
- IV (standard)
- subcutaneous (LMWH)
warfarin
- oral
what can be given to reverse heparin
protamine sulfate
what score can be used to assess bleeding risk
ORBIT score
how long before surgery should warfarin vs heparin be stopped, and what should INR be
INR should be <1.5
warfarin - 5 days before (give vit K if INR >1.5 the day before)
heparin - few hours before
describe how P450 inducers and inhibitors affect warfarin and INR
P450 Inducers - reduced warfarin activity (INR decreases)
SCARS =
smoking,
ciroc (alcohol),
anti-epileptics (carbamazepine, phenytoin),
rifampicin,
st johns wart
P450 Inhibitors - increased warfarin activity (INR increases)
ASS-ZOLES =
antibiotics (Ciprofloxacin, Isoniazid, Clarithromycin, Erythromycin),
SSRI’s (Fluoxetine, Sertraline),
sodium valproate,
-zoles (Omeprazole, Ketoconazole, Fluconazole)
management of INR and warfarin if
- major bleed
- INR > 8, minor bleed
- INR > 8, no bleed
- INR 5-8, minor bleed
- INR 5-8, no bleed
- major bleed
stop warfarin
IV vit K
PCC (prothrombin complex concentrate) - INR > 8, minor bleed
stop warfarin
IV vit K
repeat in 24hrs if still high
restart warfarin when INR <5 - INR > 8, no bleed
stop warfarin
oral vit K
repeat in 24hrs if still high
restart warfarin when INR <5 - INR 5-8, minor bleed
stop warfarin
IV vit K
restart warfarin when INR <5 - INR 5-8, no bleed
miss a couple doses of warfarin
reduce subsequent maintenance dose
how does parvovirus present
prodrome. of fever, sore throat, resp symptoms, diarrhoea
followed by rash on body and cheeks
tear drop poikilocytes are the classical blood film finding for what
myelofibrosis
painless lump in neck
worse pain on draining alcohol
night sweats
diagnosis
Hodgkins lymphoma
which B cell marker foes ritixumab target
CD20
which lymphomas are associated with EBV
Burkitt’s lymphoma (BL)
Hodgkin lymphoma (HL)
translocation between which two chromosomes is associated with burkitts lymphoma
8 and 14
what is translation between chromosome 9 and 22 associated with
CML
what is retoculocytosis a feature of
haemolysis
management of tumour lysis syndrome
aggressive hydration ad allopurinol treatment
give rasburicase if there is no improvement
pt with leukaemia presents with fatigue and lethargy and has elevated uric acid, potassium and widespread lymphadenopathy
diagnosis?
tumour lysis syndrome
PUKE Calcium = phosphorus, uric acid, potassium elevated. Calcium reduced.
describe features of ALL
children under 5
lymphadenopathy
splenomegaly
features of anaemia eg fatigue, pallor
features of thrombocytopenia eg bleeding, petechiae
features of neutropenia eg infections
what is a rouleaux formation and in which condition can it be seen
Rouleaux formation describes the appearance of clumped red blood cells. It is usually the result of abnormally high levels of proteins such as immunoglobulins in multiple myeloma.
what type of pts need irradiated blood if they’re receiving a blood transfusion and why
pts with lymphoma need irradiated blood to prevent graft-versus-host disease
which clothing factors are reduced in pts on warfarin
factors 2, 7, 9 , 10
and prothrombin agents protein C and S
pt on blood transfusion develops itchiness but obs are all stable
most appropriate initial action?
stop the transfusion (monitor to see if they develop anaphylaxis)
and give antihistamine (chlorphenamine)
what is slapped cheek syndrome
aka eryhtema infectiosum
red cheeks due to parvovirus B19
what is done to coffin a diagnosis of aplastic anaemia
bone marrow biopsy
- will show that bone marrow contains fewer blood cells of all lineages that normal
what ix is done for a patient with a gradually growing rubbery painless palpable lymph node
excisional lymph node biopsy
this allows you to see the full architecture of the lymph node and grade the lymphoma, so its better than FNA
which prophylactic abx should be taken by splenetcomy pts
penicillin or amxocillin
what does stage 3 B mean in Ann arbor lymphoma staging
lymph nodes affected on both sides of the diaphragm (ie above and below)
and patient has B symptoms (fever, night sweats, weight loss)
which type of leukaemia causes massive splenomegaly
CML
pt has weight loss and night sweats
massive splenomegaly
and raised white cell count
diagnosis?
CML
what type of leukaemia do granulocytes indicate
CML
lifespan of platelet
7-10 days
which lymphoma is characterised by the presence of atypical lymphoid cells with an irregular nucleus and a high mitotic rate on biopsy
Non-Hodgkin’s lymphoma
what condition causes dark urine in the mornings, fatigue. anaemia, elevated LDH and low haptoglobin
PNH (Paroxysmal nocturnal haemoglobinuria)
(classic triad of PNH includes haemolytic anaemia, thrombosis, and pancytopenia)
which condition are smudge/smear cells seen in
CLL
what is an aplastic crisis
parvovirus B19 IN SICKLE CELL PTS can cause sudden severe anaemia as it inhibits erythropoiesis
a pt has pancytopenia and lethargy and weight loss
next investigation?
blood film
what is the fifth disease
another word for erythema infectiosum (slipped cheek syndrome caused by parvovirus B19)
what type of lymphoma can reveal uniform densely packed follicles with loss of nodal architecture biopsy
non hodgkin
for which type of lymphoma is raised LDH a poor prognostic marker
non hodgkin
for which type of lymphoma is the Lymphocyte-depleted sub-type a poor prognostic marker
Hodgkin
child with bleeding gums, recurrent infection, petechiae and feels tired and pallor
diagnosis
This combination of lethargy and pallor suggest anaemia, easy bruising and bleeding suggests low platelets, the sore throat suggests susceptibility to infection. This could indicate a leukaemia and the child should be referred to paediatrics urgently
what should be done if pt presents with temp shortly after you start a blood transfusion for them, but have no other symptoms and what is going on with them
they have a febrile non-haemolytic transfusion reaction
this doesn’t mean they’re having a reaction to the blood. the transfusion should be slowed down and they should be given an antipyretic eg paracetamol and monitored
in which conditions are target cells found
thalassemia
liver disease
hyposplenism
haemoglobin C disorders
what type of reaction is happening to someone who develops abdo pain, riggers, fever, hypotension and tachycardia a few minutes after start of blood transfusion
acute haemolytic reaction
(due to ABO incompatibility)
which monoclonal antibody can be used to treat non Hodgkin lymphoma
rituximab
what can rasburicase be used for
can be prescribed to protect against urate build up and tumour lysis syndrome and works by converting uric acid into allantoin to prevent hyperuricaemia
what is the fired symptom of myelofibrosis
fatigue
what are pencil poikilocytes associated with
iron deficiency anaemia
for which condition is flow cytometry of CD55 and CD59 the gold standard diagnostic test for
PNH (Paroxysmal nocturnal haemoglobinuria)
what med is used in the acute management of tumour lysis syndrome
rasburicase
what is used preventionn of tumour lysis syndrome
allopurinol
hydration
what factors are involved in the intrinsic pathway - if APTT is prolonged
8, 9, 11, 12
what factors are involved in the extrinsic pathway - if PT is prolonged
3, 7
what factors are involved in the common pathway
1, 2, 5, 10, 13
which is more common, haemophilia A or B
A
what is Antiphospholipid syndrome
autoimmune
body produces anti phospholipid antibodies
increases risk of developing blood clots
what is a common type of anaemia to get after bariatric surgery
iron deficiency anaemia
what is the BCR-ABL gene associated with
CML
which condition is associated with JAK2 mutation and persistently elevated haematocrit
polycythaemia vera
what are Heinz bodies and bite cell very typical of
G6PD deficiency
what type of colour/size are the RBCs in sickle cell anaemia
normochormic normocytic
what type of colour/size are the RBCs in anaemia of chronic disease
normochormic normocytic
platelet levels in DIC
low - thrombocytopenia - as they’re being used up in the clotting
what condition does raised D dimer suggest
DIC
pt had sepsis and develops epistaxis, haemoptysis, melaena and bleeding from his cannula site
diagnosis
DIC
what condition are hypersegmented neutrophils a diagnostic feature of
megaloblastic anaemia
what does INR measure
compares prothrombin time (PT) for the patient to the average PT
what condition are shistocytes indicative of
DIC
levels of D-dimer Hb, platelets and PT/APTT in DIC?
raised D-dimer
prolonged PT / APTT (due to the consumption of coagulation factors)
low platelets
low Hb
what is methylmalonic acid
a measure of functional B12 status
what do cabot rings on blood film suggest
megaloblastic anaemia / pernicious anaemia
if there’s no improvement in Hb level after taking iron for “x” months too can start additional work-up for the underlying cause of the iron deficiency
3 months
what is facial plethora
excessive blood flow to the face - red and round face
which condition is ichting after a hot bath classically associated with
polycythaemia vera
megaloblastic anaemia vs macrocytic anaemia and causes
megaloblastic:
large nucleated RBC precursors
eg pernicious anaemia
macrocytic anaemia
enlarged RBCs
eg chronic alcoholism, liver disease
what type of anaemia is hypothyroidism associated with
non-megaloblastic macrocytosis
what type of anaemia is liver disease associated with
non-megaloblastic macrocytosis
what type of anaemia is chronic alcoholism associated with
non-megaloblastic macrocytosis
asthma symptoms in 25 year ld and a rash on her ankles, with increased eosinophil count
diagnosis
Eosinophilia with granulomatosis and polyangiitis
what antibodies are present in pernicious anaemia
Autoantibodies against intrinsic factor (IF)
(not against vit B12)
what type of anaemia does folate deficiency cause
megaloblastic anaemia
how does alcohol affect anaemia risk
non megaloblastic macrocytic sideroblastic anaemia
what is a big cause of (warm) autoimmune haemolytic anaemia
SLE
what is an isolated rise in APTT indicative of
von willebrand disease
viral illness followed by rash and reduction in platelets
diagnosis
Immune thrombocytopenia (ITP)
bone marrow failure and ring sideroblasts on bone marrow biopsy
what condition de this indicate
myelodysplasia
(Myelodysplasia is considered a “premalignant” disease that affects myeloid cells, which has around a 30% chance of developing into AML)
which anaemia can follow treatment with antibiotics for a UTI
Nitrofuratonin can trigger haemolytic crisis in G6PD - causing anaemia
what is hydroxycarbamide used for in sickle cell
long-term prevention of acute chest crises
what is the cause of red/brown macule on legs in a pt with beta thalassemia major
haemosiderosis
(deposition of iron in the skin due to the regular blood transfusion they receive for their thalassemia)
name 4 main features of HSP (Henoch-Schoenlein purpura)
palpable purpuric rash on extensor surfaces of lower limbs
abdo pain
polyarthirtis
IgA nephropathy
what type of cell would increase in a fungal infection
eosinophils
pt has hypersegmented neutrophils and complains that they cant feel their legs
diagnosis
B12 deficiency anaemia - and the B12 deficiency causes subacute degeneration of the spinal cord which causes the neurological symptoms the pt is experiencing
pt presents with bleeding, normal platelets, normal PT, prolonged APTT
what are the two differentials and how to differentiate between them
—> if deep pattern of bleeding eg haemarthrosis and muscular haematomas
= haemophilia A
—> if platelet-pattern of bleeding eg cutaneous petechiae/purpura, epistaxis, mucosal bleeding
= von willebrand disease
management of warm vs cold haemolytic anaemia
warm - prednisolone
cold - plasmapheresis (warmed blood is transfused)
are spherocytes vs schistocytes more likely to be seen in warm or cold AIHA
warm - spherocytes
cold - shistocytes
which antibodies mediate warm vs cold AIHA
warm -IgG mediated
cold - IgM mediated
most common cause of warm vs cold AIHA
warm - SLE
cold - post infectious (after Mycoplasma or EBV)
what is the only medication used for prophylaxis of sickle cell crises
hydroxycarbamide aka hydroxyurea
does intravascular or extravascular haemolytic cause red-brown urine discolouration
intravascular haemolysis
short stature, webbed neck, widely spaced nipples and has recurrerent haemarthrosis and family history of bleeding disorder
most likely diagnosis
tuners syndrome and haemophilia A
(in tuners syndrome, which only affects females, you only have one X chromosome, so can get haemophilia with only one chromosome instead of two)
what type of anaemia does hypothyroidism cause
macrocytic anaemia
tx for pernicious anaemia in pt with neurological symptoms
Hydroxocobalamin 1mg on alternate days for two weeks followed by lifelong injections every two months
tx for patents with dietary B12 deficiency
Cyanocobalamin 50 micrograms daily
A 20-year-old male presents with a microcytic hypochromic anaemia and an elevated haemoglobin A2 level on electrophoresis.
What is the most likely diagnosis?
Beta-thalassemia trait
what type of anaemia can be caused by lead poisoning
sideroblastic anaemia
pt is displaying neurological symptoms and has microcytic anaemia but raised serum iron/ferritin
diagnosis?
sideroblastic anaemia
what is the most common hereditary thrombophilia
factor V Leiden
what type of bilirubin is raised in haemolytic anaemia
unconjugated bilirubin
symptoms of anaemia, jaundice and blood film showing shistocytes
what’s going on
haemolytic anaemia
what condition are anti-cardiolipin and anti-beta2 glycoprotein antibodies associated with
antiphospholipid syndrome
most likely diagnosis in a person who presents with sudden onset Sob and pleuritic chest pain (signs of pulmonary embolism) with a family history but is otherwise all well and no PMH
and what would the likely diagnosis be instead if they’ve had recurrent miscarriages
factor V Leiden (most common hereditary thrombophilia)
antiphospholipid syndrome - if have had arterial or venous thrombosis and recurrent miscarriage
what are acanthocytes and what is a common cause of them
RBCs with projections coming out of their surface
common cause is severe liver disease
which cell is often caused following a traumatic event such as surgery
neutrophils - neutrophilia
microcytic / normocytic anaemia with low serum iron and normal serum ferritin
diagnosis
anaemia of chronic disease (The main feature of this type of anaemia is a decreased production of red blood cells, and it is often characterised by a low serum iron and normal/high serum ferritin)
what are the symptoms of multiple myeloma
CRABI → Calcium (High), Renal Impairment, Anaemia, Bone Pain, Infections
what would you see on the blood film of someone with back pain, polyuria and GI upset
Rouleax formation
(they have multiple myeloma)
levels of serum iron, ferritin and transferrin saturation in anaemia of chronic disease?
Low serum iron, high ferritin and low transferrin saturation
which condition encompasses arterial or venous thrombosis and recurrent miscarriages
antiphospholipid syndrome
pt presents with bloody diarrhoea, intravascular haemolysis, thrombocytopenia and renal/cerebrovascular involvement
diagnosis?
haemolytic uraemia syndrome
- caused by E coli
burr cells vs acanthocytes, appearance and cause
acanthocytes
- spicules vary in length and width
- project non uniformly from cell surface
- severe liver disease
Burr cells
- regularly spaced, smoothly rounded projections
- pyruvate kinase deficiency, kidney disease
if a pt is deficient inB12 and folate, do you replace one of them first or together?
B12 first, then folate
bc B12 deficiency can cause subacute degeneration of spinal cord
and folate metabolism requires B12 so it will use it up putting them at more risk of spinal cord degeneration
what condition causes frontal bossing (prominent forehead)
haemophilia B
describe the appearance of Howell jolly bodies
single, peripherally located rounded icnlsuuion in the RBC
pt has a mechanical heart valve, what would you expect to see on her blood film
shistocytes
(Schistocytes are fragmented red cells seen in intravascular haemolysis, such as haemolytic anaemia. They are also seen in patients with mechanical heart valves due to mechanical haemolysis of the cells)
what does raised LDH and raised reticulocytes mean
haemolytic
what does raised LDH, reticulocytes and presence of schistocytes mean
intravascular haemolysis
what does raised LDH, reticulocytes and presence of spherocytes mean
extravascular haemolytic
mech of action of desmopressin when used for haemophilia A
Releases von Willebrand factor (von willebrand factor is a carrier protein for factor 8)
pt with beta thalessemia, her periods have stopped, she has leg swelling and shortness of breath
most appropriate tx?
desferrioxamine
describe the difference between HbAS, HbSC, HbSS
HbAS - sickle cell. trait, no symptoms
HbSC - milder form of sickle cell disease
HbSS - sickle cell disease
left shift vs right shift in terms of neutrophils
left shift =
immature neutrophils,
unlobed band like nucleus
seen in acute infection
right shift =
hyper mature neutrophils
multi lobed nucleus
seen in megaloblastic anaemia
what is a Leukoerythroblastosis film and when is it seen
combination of severe left shift with the presence of nucleated red blood cells
seen in infiltrative marrow disease
likely diagnosis if a pt develops a venous thromboembolism after being out on warfarin
protein C deficiency
(Protein C deficiency is a hereditary thrombophilia associated with low levels of protein C, a serum anticoagulant. Warfarin reduces production of factor II, VII, IX, X, protein C and protein S. there is a period around 1 to 2 days after initiation of warfarin therapy where patients become procoagulable)
likely diagnosis if a pt with sickle cell disease presents with RUQ abdo pain
cholecystitis
(a common complication of sickle cell disease, due to sickling and sludging of red blood cells in the microvasculature of the gallbladder)
EPO level in polycythaemia vera
low
which has more risk of VTE, 2 days of bed rest or a surgery
surgery
(bed rest would be strong risk if was over 5 days)
what investigation confirms diagnosis of leukaemia
bone marrow biopsy with immuno-phenotyping
first line management of idiopathic autoimmune haemolytic anaemia
corticosteroids
which sickle cell crisis can be triggered by the cold
vaso-occlusive crisis
what is carbimazole associated with
causes neutropenia and agranulocytosis
pt with sickle cell presents with sudden anaemia and a drop in reticulocyte count
diagnosis?
aplastic crisis
which medications trigger G6PD
ciprofloxacin, sulfonylureas, sulphasalazine
management/tx of hereditary spherocytosis
folate supplementation
splenectomy
pt has SLE and has a positive direct antiglobulin test, with symptoms of breathlessness and dizziness
diagnosis?
warm autoimmune haemolytic anaemia
pt has direct anti globulin test positive and hands turn white when its cold
which immunoglobulin is associated with this
IgM (cold AIHA)
haemolytic anaemia, thrombocytopenia and neurological features, normal PT/APTT
which condition does this suggest
TTP (thrombotic thrombocytopenic purpura)
what is ADAMTS-13 deficiency the same as
TTP (thrombotic thrombocytopenic purpura)
which blood cells can prednisone cause a rise in
neutrophils - can cause neutrophilia
headaches, itching in hot baths/showers, facial plethora, arterial/venous thrombosis
what do these symptoms suggest
polycythaemia
what condition are ANK1 mutations found in
hereditary spherocytosis
which condition causes increase in platelets - thromboctytosis
essential thrombocytosis
if a pt with SCD presents with sudden drop in Hb, what do you need to measure
reticulocytes, this will inform you if there is an appropriate response to the haemoglobin drop
