Haem Laz Flashcards
What do multipotent stem cells differentate into
- common myeloid progenitor
- common lymphoid progenitor
what do commoon myeloid cells differentiate into
MYELOBLASTS (monocytes, neutrophils, basophils, oesinophils)
ERYTHROCYTES
MEGAKARYOCYTES
What do common lymphoid progenitor differentiate into?
T cells
B cells > plasma cells
What cells does AML affect
Common myeloid progenitor and myeloblast
What cells does CML affect
Monocytes, neutrophils, basophils, oesinophils
What cells does ALL affect
Common lymphoid progenitor
What cells does CLL affect
B cells, T cells
Summarise AML presentation
Adults
BM failure (pancyctopoena)
acute onset
Auer rods
Summarise ALL presentation
Children
BM failure
Failure to thrive
Summarise CML presentation
Adults
t(9,22) transolcation - PHIILADELPHIA CHROMOSOME
Often incidental finding, occasionally BM failure
Tx IMATINIB
Summarise CLL presentation
Adults
Often incidental finding, occasionally BM failure
SMUDGE CELLS
What does MAHA stand for
Microangiopathic Haemolytic Anaemia
WHat is MAHA
MECHANISM NOT DISEASE
RBC breakdown in small vessels
What does HUS stand for
Haemolytic uraemic syndrome
What is HUS caused by
E coli 0157:H7 which produces shiiga like toxins
this causes endothelial injury in glomerular vessels
leading to platelet plug formation > THROMBOCYTOPOENIA
RCs destroyed as they try to get past > MAHA
Poor kiidney perfusion > renal failure
What is the triad of HUS and what othher Sx may occur
HUS: MAHA + thrombocytopoenia + renal failur
+ diarrhoea (due to e coli)
What is TTP
Thrombotic thromobocytopoenic purpura
What occurs in TTP
ADAMTS 13 is reduced (unkown cause, cancer, pregnancy)
AdamTS13 is usually used to break dowon vWF multimers
This means that there are excessve vWF multipmers > form platelet plug > platelet consumton, RC destruction, poor end organ perfusion
Sx of TTP
MAHA + Thrombocytopoenia + renal failure
+ RASH + CONFUSION (due to reduced brain perfusion)
What is DIC caused by
increased exposure to tissue factor, such as in
- pregnancy
- sepsis
- tumour
- pancreatitis
What does DIC stand for, and what occurs
Disseminated INtravascular Coagulaton
increased exposure to tssue factor
activation of clotting cascade
- increased platelet consumption > THROMBOCYTOPOENAI
- increased coag factor consumption > decreased coagulation factors
What is multiple myeloma
Cancer of plasma cells
resulting in excessive monoclonal Ig production
What is the progression of monoclonal Ig disease
- MGUS
- Smouldering myeloma
- MM
- B cell leukaemia
how does MGUS present
NO CRAB SX
- M protein <30g/L
- BM plasma cells <10%
how does smouldering myeloma present
M protein >30g/L
BM plasma cells >10%
annual risk of progression to MM is 10%
no CRAB SX
How does mutliple myeloma present
CRAB SX
M protein >30g/L
>60% plasma cells in BM
>1 focal lesion on MRI
What symptoms occur with MM
CRAB
calcium elevared
renal failure
anaemia
bone lesions (lytic)
what Ix myst you get in MM
- FBC, UE, bone profile, ESR, serum Ca
- Serum / urine electrophoresis
- Whole body low dose CT
- Bone marrow aspirate and biopsy
What does Serum / urine electrophoresis show in MM
shows a single monoclonal band (MONOCLONAL GAMMOPATHY)
what proteins are present in MM
Bence Jones proteins
what is myelodysplasia
abnormal differentiation of cells along myeloid line
this causes a BM disorder with PANCYTOPOENIA and FUNCTONALLY IMMATURE CELLS
what is myelofibrosis
clonal BM disorder characterised by fibrous scar tissue deposition
overexpansion of clone in BM > fibrous scar tissue deposits in reesponse
> > PANCYTOPOENIA, TEAR DROP CELLS; DRY TAP; MASSIVE SPLENOMEG to compensate for low RBC
causes of MICROCYTIC anaemia
TAILS
Thalassaemia
Anaemia of Chronic Disiease
Iron Deficiency anaemia
Lead poisoning
Sideroblastic anaemia
causes of NORMOCYTIC anaemia
Iron deficiency (early)
Chronic disease (early)
Marrow failure
Renal failure
Aplastic anaemia, Acute blood loss
Leukaemia, Myelofibrosis
causes of MACROCYTIC anaemia
Alcoholics May Have Liver Failure
Alcoholism
Myelodysplastic sydrome, MM
Hypothyroid, haemolytic anaemia
Liver Failure
Folate / B12 def
what size are RBC in haemolytic anaemia and why
MACROCYTIC or normocytuic
what are causes of haemolytic anaemia
INHERITED: defect of RBC which cauze them to be broken down
- membrane (hereditary spherocytosis)
- cytoplasm / enzyme (G6PD deficiency)
- Haemoglobin (SCD or thalassaemia)
Aquired (defect in environment the RBC are in, either immune or non immune mediated)
why must you be careful measuring ferritin in IDA?
if no illness, fair to check
if ill - be aware that FERRITIN is an ACUTE PHASE PROTEIN so check TIBF, TTF, iron instead
what are the two types of immune-mediated anaemia
AIHA (warm and cold)
What test can you do for AIHA
Coomb’s test / direct antiglobulin test
Explain features of WARM AIHA
GHANA: IgG, 37 deg
spherocytes
outside of europe: EXTRAvascular haemolysis
explain features of COLD AIHA
Mountain: IgM
under 37 deg
inside europe: INTRAvascular
what causes tumour lysis syndrome
recent chemotherapy, causing destruction of lots of cells
what are electroolytes like in tumour lysis syndrome
HIGH K+
hgh phosphate
low calcium
what does positive clinical TLS require
At least one of the following.
- >1.5x ULN creatinine
- cardiac arrythmia / sudden death
- seizure
Mx tumour lysis syndrome
IV allopurinol (if high risk)
PO allopurinol (if low risk) - can be given prophylactically
when do you ned to transfuse packed RBC
No ACS : for Hb <70
ACS: Hb <80
what level do you need to maintain platelets at for:
- pre-procedure
- pre-procedure if surgery at critical site
- no active bleedsing / planned surgery
- pre-procedure: >50
- pre-procedure if surgery at critical site >100
- no active bleedsing / planned surgery >10
what is a THROMBOPHILIA
LOVES THROMBI > propensitiy to develop clots
causes of thrombophilia - inherited
Factor V Leiden
Prothrombin gene mutation
Protein C/S deficiency
Antithrombin III deficiency
causes of thrombophilia - aquired
antiphospholippid syndrome
Drugs (COCP)
what is heparin inducted thrombocytopoenia (HIT)
a PROTHROMBOTIC condition
how does HIT ooccur
AB form against complexes of platelet factor 4 and hepatin > induce platelet activation > low platelets but LOTS OF THROMBI FORMATION
Classic HIT presentaton
> 50% reduction in platelets
Thrombosis
Skin allergy
How do you manage HIT
STOP HEPARIN, chaange to Argatroban (thrombin inhibitor)
what category are anti D antibodies
IgG (dont cause direct agglutination - cause a delayed haemolytic transfusion reaction instead)
what are antibodies against A, B on blood
IgM against normal RBC antigens
IgG against atypical RBC antigens
List acute transfusion reactions (<24h)
Acute haemolytic reactions (ABO incompatibility)
Allergic / anaphylactic
Infection (bacterial)
Febriile non haemolytic reaction
Respiratory (TACO, TRALI)
what occurs in sickle cell anameia
defective beta globin gene (glutamine to valine), which leads to abnormal folding of RBC into sickle shape
What is mode of inheritance of sickle cell
AR
what occurs in thalassaemiai
reduced haemoglobin synthesiis
which type of malaria is most fatal
Plasmodium falciparum
what other types of less fatal malaria exist
Plasmodium vivax
ovale
knowlesi
describe symptoms of P falciparum
cyclical fevers (every 48h)
splenomegaly
neuro involvement (altered GCS and seizures)
DV
metabolic acidosis
shock
how do you treat malaria falciparum
mild: oral MALARONE / artemisin combination therapyu
severe: IV Artesunate
how do you treat other types of malaria
chloroquine
classical general S/S of malaria
onset 7-10 days after inoculation
fever (cyclical or continuous with spikes)
DV
flu like sx
jaundice
anaemia
drowsiness, confission
how do you investigate for malaria
3 thick and thin blood films (thick: presence; thin: species)
Malaria rapid antigen detection test
How do you prevent malaria
Quinine prophylaxis
typhoid fever cause
salmonella typhi / paratyphi
how is typhoid transmitted
faeco oral
sx typhus
fever
bradycardia
headache
dry cough
weight loss, anorexia
GI sx (diarrhoea or constipation)
classical derm presentation of typhuss
rose spots
Mx typhus
IV ceftriaxone
where is typhus still found
pakistan
india
bangladesh
organism that causes dengue fever
arbiirus flavivirus - aedes aegiptii mosquito
sx dengue
short incubation period
Primary infection: headache, sunburn rash, fever and myalgia
Secondnary infection: DENGUE HAEMORRHAGIC FEVER, very unwell with hypotennsion and massive haemorrhages
how do you treat dengue
supportive (fluids and monitoring) >ITU
what are ‘Tear-drop’ poikilocytes found in
myelofibrosis
what is ITP
Immune Thrombodytopoenia
essentially antibodies against GLPIIb/IIIa > thrombocytopoenia
how does ITP present
petechhiae, purpura, bleeding
how do you manage ITP
oral pred
IVIG
how does acute haemolytic reaction present
DURING/RIGHT AFTER TRANSFUSION
- fever
- abdo pain
- hypotension
how do you confirm an acute haemolytic reaction
COOMBS +ve
How do you manage acute haemolytic reaction
- stop transfusion
- fluid resus
what is the most common BLEEDING DISORDER
von Willenbrand isease
mode of inheritance of vWD
AD
what is the normal role of vWF
to promote platelet adhesion to damaged endothhelium
types of vWD
- Reduced quantity vWF
- poor quality vWF
- total lack vWF
mx neutropoenic sepsis
Tazocin
what drughs cause haemolysis in G6PD deficiency
Ciprofloxacin
S drugs: sulphoonamides, sulphonylurea, sulphasalazine
how do you confirm G6pD deficiency
G6PD levels now and in 3 months
what transfusion reaction is someone with IgA deficiency more at risk of
ANAPHYLACTIC REACTION (because they are more likely to have anti-IgA that attack the donor blood)
which type of vWD are AD and which are AR?
AD: type 1 and 2
AR: type 3 (total lack vWF)
what do ix for vWF reveal
prolonged APTT
prolonged bleeding time
how can you manage vWF
tranexaminc acid, desmopressin (which induces vWF release), F8 concentratee
important ix in MM and their findinga
- serum / urine electrophoresis (shows monoclonal gammopathy of IgG or IgA and Bence-Jonees protein)
- FBC, UE, Ca, bone profile, blood film, ESR
- bone marrow aspirate and biopsy
- whole body CT/MRI
- X ray head
what does X ray head show iin MM
a RAINDROP SKULL (similar to pepper pot skull in 1HPTH)
sx of polycythaemia
hyperviscosity: headache, light headedness, visual changes, fatigue, dyspnoea
histamine release: aquagenic pruritus, peptic ulceration, splenomegaly
What are blood findings on polycythaemia
Raised Hb and Htc
what mutation is iportant in distinguishing the cause of polycythaemia
JAKV617F +ve = polycythaemia vera
JAKV617F -ve = True polycythaemiia (hypoxia, renal disease, tumour) or pseudopolycythaemia (dehydration)
what does polycythaemia vera risk progressing to
myelofibrosis
AML
mx polycythaemia
venesection
aspirin (to reduce risk of thrombosis)
what is the FASTEST reaction to blood transfusion that can occur
anaphylactic reaction (SOB, wheeze, facial oedema. IMMEDIATE)
or allergic (may be mild - just pruritic rash)
what is the decond fastest reaction to blood transfusion that can occur
Acute haemolytic reaction(due to ABO incompativiliy, IgM mediagted) - within mins
sx Acute haemolytic reaction
- Fever
- Abdo pain
- low BP
how do you mx Acute haemolytic reaction
stop transfusion
fluid resus
how does febrile non haemolytic transfusion reaction pesent
rise in temp by 1 degree without circulatory collapse
+- chilld and rigors
how do you manage febrile non haemolytic transfusion reaction
stop or slow transfusion, give paracetamol
what kind of transfusion is most likely to cause bacterial contamination
platelet transfusion
how do you manage TACO
IV furosemide
slow / stop transfusion
oxygen
how do you manage TRALI
stop transfusion, supportive
how doees a delayed type haemolytic transfusion reeaction present
same as acute but milder
occurs within one week of transfgusion
how does GvHD present
within one week of transfusion
- rash
- skin desquamation
- diarrhoea
- fever
causes of MASSIVE SPLENOMEGALY
myelofibrosis
chronic myeloid leukaemia
visceral leishmaniasis (kala-azar)
malaria
Gaucher’s syndrome
how do you remove the risk of GvHD and what patients need this adaptation
by IRRADIATING
patients with hodgkin /immunocompromised/neonates <28days
what patients need CMV neg blood
intrauterine / neonates / preg
what do you give in pts with IDA who cannot tolerate oral iron / time interval is too short
give IV iron 1g
repeat 1 week later
how does ITP present
petechiae
purpura
bleeding q
how do you manage ITP
Oral pred
IVIG
what are the four types of hodgkins lymphoma
Nodular sclerosing
Mixed cellularity
lymphocyte predominant
lymphocyte depleted
what cells are classical of hodgkins and what do they looi like
REED STERNBERG (binucleated Owl’s eye cells)
= large multinucleate cells with prominent eosinophilic nucleoli.
what is the staging system of hodgkins
ANN ARBOUR
explain ann arbour staging
1: 1 site on one side of the diaphragm
2: >1 site, on one side of diaphragm
3: both sides of diaphragm
4: BM, lungs, liver involvement
what are B symptoms in hodgkins
fever >38
night sweats
unintentional WL >10% body weight in 6 months
what do B symptoms suggest in terms of prognosis
POOR
how do you manage an allergic reaction to the transfusion
stop the transfussion
administer antihistamine
which type of hodgkins has the best prognosis
Lymphocyte predoiminant
what part of the intestine is iron absorbed in
in the DUODENUM
what part of the intestine is folate absorbed in
JEJUNUM
what part of the intestine is B12 absorbed in
ILEUM
what vitamin will someone with al ilieocaecal resection from chrons be deficient in
B12
blood findings for EBV glandular fever
RAISED lymphocytes, no neutrophils
sx glandular fever
fatigue
recurrent tonsillitis
how is hodgkins different to NHL
Hodgkin’s lymphoma has:
- alcohol-induced pain in the node
- ‘B’ symptoms typically occur earlier
- Extra-nodal disease rare
how do you invesitgate lymphoma
- FBC, CRP ESR, blood film, LDH
- exisional node biopsy
- CT chesst abdo pelvis (staging)
- HIV test
what is the most aggressive NHL
Burkitt’s
who does Burkitts occur in
young immunosuppressed
EBV and HIV associations
what are high grade NHL
DLBCL and mantle cell lymphoma
what is the MOST COMMON type of lymphoma
DLBCL
what virus is DLBCL asociated with
EBV
types of low grade lympha
follicluar
malt
SLL/CLL
how do you treat CML
Imatinib (tyrosine kinase inhib)
what lymphoma has a starry sky appearance on LN buopsy
Burkitts
what findings does waldenstrom’s macroglobilinaemia have
monoclonal IgM paraproteinaemia
systemic upset: weight loss, lethargy
hyperviscosity syndrome e.g. visual disturbance
the pentameric configuration of IgM increases serum viscosity
hepatosplenomegaly
lymphadenopathy
how must you manage beta thalassaemia major
LIFELONG BLOOD TRANSFUSIONS
+ desferroxamine to avoid iron overload
what electrolyte abnormality may occur following transfusion of large volume RBC
HYPERKALAEMIA (because packed RBC have high potassium)
what is the most common inherited thrombophilia, and what is pathophy
FACTOR V LEIDEN (heterozygous)
– due to resistance to Protein C
what does the presence of band cells indicate
CML
what kind of leukaemia does LOW LYMPHOCYTES point to
AML or CML
what is sideroblastic anaemia
inability to form haem > form ring sideroblasts instead
causes of sideroblastic anaemia
congenital
myelodysplasia
alcohol
lead
anti TB meds
ix in sideroblastic anaemia
FBC (hypochromic microcytic)
iron studies (raised ferritin, raised iron, raised transferrin sat)
blood film (Basophilic stippling)
BM staining (ring sideroblasts)
what is aplastic anaemia
pancytopoenia + hypoplastic BM
causes of aplastic anaemia
congenital
- Fanconi
- dyskeratosis congenita
drugs
- cytotoxics
- chloramphenicol
- sulphonamides
- phenytoin
viral
- parvovirus
- hepatitis
which pathway does PT measure
the EXTRINSIC PATHWAY (i.e. the short one, activated by tissue factor)
which pathway does APTT measure
the INTRINSIC PATHWAY (long)
what factors are involved in the INTRINSIC PATHWAY
12, 11, 9, 8, 10
which factors are involved in EXTRINSIC PATHWAY B
tissue factor
F7
explain the common pathway
PROTHROMBIN converts to THROMBIN (by F10a)
FIBRINOGEN converts to FIBRIN (by thrombin)
FIBRIN cross links the clot
what are causes of prolonged PT only (i.e. issue is in the extrinsic pathway)
inherited (F7 deficiency)
Aquired (mild viit K, liver disease, warfarin, DIC)
what are causess of prolonged APTT ONLY (issue in intrinsic pathhway)
deficiency of any of the factors invlved
vWD
causes of prolonged PT AND APTT
deficiency of fibrinogen, prothrombin, F5, F10
liver disease
DIC
anticoagulants
what is heparin MoA
inhibits antithrombin (whhich blocks thrombin)
how many globin chains is each Hb made up of
4 globin chains
what are the types of Hb and which globin chains do they contain
HbF= 2 alpha, 2 gamma (foetal, drops at 3m of life)
HbA = 2alpha, 2 beta (adult)
HbA2 = 2alpha, 2 delta (small portion of adult)
what occurs in beta thalassaemia
beta globin deficiency !! > free alpha chains form inclusions > haemolysis of RBC
haemolysis means
- raised bilirubin > jaundice
- raised iron > haemochromatosis
increased RBC production to compensate > HEPATOSPLENOMEGALY
what sx do you get with beta thalassaemia then
jaundice, haemochromatosis
hepatosplenomegaly
what are blood findings of thalassaemia
microcytic anaemia
target cells
raised iron
what are the combinations of beta blobin mutations you can get in thalassaemia
beta+ = less than normal
beta0 = no beta chains
what are the types of beta thalassaemia
beta thalassaemia major = beta0beta0
beta thal intermedia ? beta+beta+
beta thal minor = beta+beta or beta0beta
how does beta thalaasaemia present on electrophoresis
low HbA
raised HbF, HbA2
what type of thalassaemia is incompativle with life
alphha thalassaemia major = Hb Barts (x4 alpha globin gene deletion) > hydrops fetalis, death in utero
