MedEd Haem 2 Flashcards
preg lady in first trimester has low Hb and high MCV. not taken any multivits / supplements. Dx?
folate deficiency
5M has fatigue, SoB, jaundice. father had splenectomy when younger. blood film shows spherocytes. most sensitive Ix?
eosin-5-maleimide
18M holiday to malawi where he turned yellow, had brown urine and felt tired. no PMH. took antimalarial prophylaxis.
BT - normocytic anaemia with unconjugated BR. DAT negative.
Dx?
G6PD deficiency
which lab finding would you not expect to see in AIHA:
reticulocytes
raised conjugate BR
positive DAT
low Hb
raised LDH
raised conjugated BR
confused pt has extreme lethargy, oliguric.
blood film shows schiostocytes
BT shows thrombocytopaenia, rapid rise in urea and creatinine
Dx?
TTP
how do you manage TTP
plasma exchange
define anaemia
reduced ability to deliver oxygen due to lower number of RBCs / decreased Hb
anaemia cut off for men and women
men <130
women <120
3 mechanisms for anaemia
blood loss
decreased RBC production
increased RBC destruction
DDx of microcytic anaemia
iron def
thalassaemia
sideroblastic anaemia
key Ix for microcytic anaemia
peripheral blood smear
iron studies
commonest cause of iron def anaemia
blood loss
buzzword of iron def anaemia on blood film
pencil cells
iron study results in iron def anaemia
low iron
low ferritin
high transferrin
high TIBC
buzzword of FBC for iron deficiency
reactive thrombocytosis
what is transferrin
molecule that binds iron
what is TIBC
directly proportional to transferrin
mx of iron def anaemia
investigate underlying cause
iron supplements
blood film buzzword of thalassaemia
basophilic stippling (purple spots - ribosomal material)
target cells
iron studies of thalassaemia
all normal
causes of target cells
thalassaemia
hyposplenism
hepatic failure
haemaglobinopathies
mx of thalassaemia
iron supplementation
regular transfusions
iron chelation
iron studies of anaemia of chronic disease
low Hb
low iron
normal or low TIBC / transferrin
normal transferrin saturation
normal or high ferritin
why can ferritin be high in anaemia of chronic disease
its an acute phase protein so high in the acute phases of chronic disease
what is ferritin
iron storage molecule
what is sideroblastic anaemia
have lots of iron in the body but you can’t incorporate it into haemaglobin - end up with iron ringed around cells
blood film buzzword of sideroblastic anaemia
basophilic stippling (purple dots)
iron studies of sideroblastic anaemia
high iron ** key one
high / normal ferritin (differentiates between iron def and this)
low transferrin / TIBC
BM biopsy of sideroblastic anaemia (buzzword)
ringed sideroblasts
mx of sideroblastic anaemia
treat underlying cause
regular transfusions
causes of sideroblastic anaemia
congenital
lead poisoning
high alcohol intake
ddx of macrocytic anaemia
megaloblastic anaemia - vit b12 / folate def
alcohol
hypothyroidism
pregnancy
key Ixs for macrocytic anaemia
peripheral blood film
LFTs
TFTs
how does alcohol cause macrocytic anaemia
too much deposition of cholesterol around RBCs causes increased size of cells
how does hypothyroidism cause macrocytic anaemia
low T4
T4 also stimulates production of erythropoietin, so less erythropoeitin = less RBC production and bigger
what foods have high b12 vs folate
b12 = eggs, meat, fish
folate = leafy green veg
key test to differentiate b12 from folate deficiency and result
serum methylmalonic acid (high in b12)
how does the duration of sx vary between b12 and folate def
folate def = months
b12 def = years
key sx difference between b12 and folate def
b12 def associated with neurological changes
what test can be used to determine cause of b12 def and why
schilling test - positive if b12 def due to pernicious anaemia
(outdated test)
what drug in the histoy would indicate folate def and why
phenytoin - inhibits folate absorption
mx of b12 / folate def
vitamin supplementation
LFT results of alcoholism causing macrocytic anaemia
AST more than double ALT
raised AST, ALT and GGT
key sx to identify hypothyroidism
thinning of outer 1/3rd of eyebrows
ddx of normocytic anaemia
haemolytic
- inherited
- acquired: immune / non immune mediated
non haemolytic
- anaemia of chronic disease
- failure of erythropoeisis
Ix for normocytic anaemia
peripheral blood smear
DAT
CRP, ESR
causes of anaemia of chronic disease
infection
inflammation
cancer
why does chronic disease cause anaemia
lots of cytokine and free radical production
molecule called hepcidin produced
hepcidin inhibits erythropoiesis
less RBCs produced –> anaemia
iron studies of anaemia of chronic disease
high iron
high ferritin **key one
low transferrin and TIBC
mx of anaemia of chronic disease
tx underlying cause
causes of inherited haemolytic anaemia
membrane: hereditary spherocytosis
cytoplasm / enzymes: G6PD def
haemoglobin
causes of acquired haemolytic anaemia
immune
- AI: warm vs cold HA
- alloimmune: ABO / RhD incompatibility
non immune
- microangiopathic vs macroangiopathic
- infection
causes of intravascular haemolysis
alloimmune - ABO / RhD
autoimmune
hereditary spherocytosis
causes of extravascular haemolysis
malaria
G6PD def
drugs
PNH - paroxysmal noctural haemaglobinuria
PC of paroxysmal nocturnal haemaglobinuria
haemaglobinuria in the morning
low haptoglobin
high LDH
what causes hereditary spherocytosis
defect in vertical interaction of RBC membrane
most sensitive test for hereditary spherocytosis
eosin-5-maleimide
what other test would be + in hereditary spherocytosis
osmotic fragility test
blood smear of hereditary spherocytosis
spherocytes
polychromasia
mx of hereditary spherocytosis
folate supplement
splenectomy
inheritance pattern of hereditary spherocytosis
AD
inheritance of G6PD
X linked recessive
PX of g6pd def
episodes of acute haemolysis after an exposure to oxidative stress
triggers of g6pd flares
fava beans
mothballs
drugs - anti malarials (primiquine), doxycycline, ciprafloxacin
buzzwords of blood film of g6pd def
heinz bodies
bite cells
BR and haptoglobin levels in g6pd def
high unconjugated BR
low haptoglobin
mx of g6pd def
avoidance of triggers
supportive care
pathophysiology of g6pd def causing haemolysis
g6pd is used in pentose phosphate pathway
generates NADPH
used to make glutathione
glutathione prevents RBCs being damaged by oxidative stress
–> therefore g6pd def = vulnerable to damage by oxidative stress
what test is positive in AIHA
DAT
difference in mediator in warm / cold AIHA
warm = IgG
cold = IgM
association of warm AIHA
CLL (** key), SLE, methyldopa
association of cold AIHA
mycoplasma, EBV, hep C
how is the haemolysis different in warm and cold AIHA
warm = extravascular
cold = intravascular
mx of AIHA
treat underlying cause
steroids
rituximab ** key one
which type of AIHA is more severe
warm
DAT result of non AIHA
negative - no ABs produced
causes of non AIHA
infection eg malaria
structural issue –> MAHA
what is mechanism of MAHA
damage to endothelial surface –> fibrin deposition –> platelet aggregation –> fragmentation of RBCs
buzzword blood film features of MAHA
schistocytes
thrombocytopaenia
3 conditions that can cause MAHA
HUS
TTP
DIC
how can you distinguish DIC from HUS/TTP
HUS / TTP = normal APTT, PT, fibrinogen
DIC would have really abnormal levels
bacterial cause of HUS
e.coli O157:H7
who gets HUS
children
adults can get it but its less common and more severe
PC of HUS
sx after diarrhoeal illness
triad: MAHA, thrombocytopaenia, AKI
mx of HUS
supportive - self limiting in kids
do not give ABx to treat the diarrhoeal illness
cause of TTP
deficiency of ADAMTS13 (inherited or acquired)
**buzzword
PC of TTP
pentad
- MAHA
- thrombocytopaenia
- AKI
- neuro sx
- fever
mx of TTP
supportive care
plasma exchange
what is DIC
MEDICAL EMERGENCY
activation of coagulation and fibrinolysis
triggers of DIC
sepsis (most common)
trauma - head injury, fat embolism
obs - amniotic fluid emboli, placental abruption
malignancy - APML
BT results of DIC
low platelets
low fibrinogen
high PT and APTT
high D dimer
PC of DIC
bleeding from mouth / lines
massive bleeding from anywhere
clotting studies for DIC
prolonged APTT, PT, TT
decreased fibrinogen & platelets
increased FDP
film - schistocytes
what does the DAT test show
AI mediated haemolysis
what does urinary haemosiderin / Hb show
intravascular haemolysis
what does + osmotic fragility test show
hereditary spherocytosis
what does PK deficiency cause
chronic haemolytic anaemia (in contrast to G6PD which is episodic)
what does heinz bodies stain suggest
oxidative haemolysis
what is hams test for
paroxysmal nocturnal haemaglobinuria
which is true about alpha thalassaemia:
caused by defect on chr 11
increased destruction of beta globin chains
decreased gamma globin chains
4 mutated genes can lead to hydrops fetalis
increased prod of alpha globin chains
4 mutated genes can lead to hydrops fatalis
XR features of beta thal major
hair on end - looks like spikey hair on top of bone, rathe than smooth
best Ix to diagnose beta thal
high performance liquid chromatography
3 types of hb with make up of each and who has each
HbF (a2g2) - foetus, infant
HbA (a2b2) - late foetus, infant, child, adult [default one]
HbA2 (a2d2) - infant, child, adult
dx of haemglobinopathies
hb electrophoresis (high performance liquid chromatography)
who gets more HbA2 and why
beta thalassaemia pts - they can’t make the beta chains seen in HbA
what chromosome is affected in beta thal
11
key features of the 3 types of beta thal
major - severe anaemia needinf regular blood transfusions
intermedia - mod reduction in beta globin chain prod
minor - benign but genetic implications
dx of beta thal
high performance liquid chromatography
mx of beta thal
regular blood transfusions
iron chelation
folate supplementation
what chromosome is affected in alpha thal
16
how many genes code for beta vs alpha thal
beta = 2
alpha = 4
give the name for 4 / 3 / 2 / 1 alpha genes affected in alpha thalassaemia
4 = Hb Barts
3 = HbH
2 = trait
1 = silent
features of the 4 types of alpha thalassaemia
Hb Barts = fatal in utero, hyrops fetalis
HbH = severe anaemia in childhood, hepatosplenomegaly
trait = mild anaemia
silent = aSx
mx of alpha thalassaemia
regular blood transfusions
iron chelation
folate supplementation
inheritance of sickle cell
AR
pathophysiology of sickle cell (mutation, location, outcome)
glutamine –> valine mutation at codon 6 on beta globin chain
produces HbS
forms of sickle cell Hb produced
HbSS
HbAS
HbSC
HbSbeta
PC of sickle cell disease
haemolytic crisis
sequestration crisis
aplastic crisis
infection
2 key buzzword infections that occur in sickle cell disease pts
strep pneumo sepsis
salmonella osteomyelitis
what ix is used in sickle cell disease and in which types is it +
sickle solubuility test
HbSS
HbAS
mx of sickle cell disease
vaccination
folate supplementation
hydroxyurea
supportive in acute crisis
19M with acutely swollen knee. PMH bleeding after dental extraction. what factor is most likely to be deficient?
factor 8
what is the most common inherited thrombophilia
hereditary activated protein c resistance (factor V leiden)
list disorders of primary and secondary haemostasis
primary - platelets adhesion / aggregation
secondary - coagulation cascade
inherited disorders of thrombosis
factor V leiden (most common)
anti thrombin deficiency
protein C / S deficiency
acquired disorders of thrombosis
HIT
malignancy
immobilisation
what do dysfunction of primary vs secondary haemostasis cause
primary = bleeding disorders (superficial bleeding)
secondary = coagulation disorders (deep bleeding)
causes of dysfunctional primary haemostasis
vWF disease
ITP / HIT
causes of secondary haemostasis dysfunction
inherited - haemophilia A / B
acquired - liver disease, vit K def
defect in haemophilia A vs B
defect in factor 8 (A) vs 9 (B)
what is the problem with platelets in ITP
decreased survival of platelets
what is the problem with platelets in DIC
increased consumption
what can cause acquired defective platelet function
aspirin
CKD
what can cause inherited defective platelet function
thrombasthenia
3 subtypes of vWF disease and what they are
type 1 = quantitative defect
type 2 = qualitative defect
type 3 = mixed defect
inheritance of the types of vWF disease
type 1 and 2 = AD
type 3 = AR
PC of vWF disease
mucocutaenous bleeding
usually female
bloods of vWF disease
low platelets
increased bleeding time
increased APTT
normal PT
low factor 8
2 DDx of vWF and how you can distinguish them
bernard-soulier disease (large platelets)
glanzmann’s throbasthenia (normal ristocetin)
[low yield]
what protein is abnormal in vWF
ristocetin
mx of vWF disease
desmopressin
vWF and factor 8 concentrates
who gets acute ITP
children, sex even
who gets chronic ITP
adults, females >males
trigger of acute vs chronic ITP
acute = infection
chronic = no trigger
mx of acute ITP
self limiting
tx steroids, IVIG if platelets count really low
mx of chronic ITP
steroids
IVIG
splenectomy
progression of chronic ITP
long term relapsing remitting
inheritance of haem A
x linked recessive
pc of ham A
haemarthrosis (bleeding into joints)
spontaneous, deep bleeding
blood results of haem A
normal platelet count, bleeding time, PT
prolonged APTT
which haemophilia is more common
A
mx of haem A
factor 8 concentrate - can become resistant to this eventually though
how can you tell haem A from B clinically
you can’t
what is vit k used for
synthesis of factors 2, 9, 10 and protein C/S
causes of vit k def
malabsorption
warfarin
ABx
which factor is first to be depleted in vit k def
factor 7
** key exam Q
blood results of vit k def
normal platelets, bleeding time
prolonged APTT and PT
ddx of vit k def and how to tell them apart
liver disease (low platelets)
scurvy (corkscrew hair) **buzzword
mx of vit k def
vit k replacement
PCC
FFP
inheritance of factor V leiden
AD
pathophysiology of factor V leiden
resistance to protein C –> failure to degrade factor V –> hypercoagulable state
what are factor V leiden pts predisposed to
VTE (arterial rare)
mx of factor v leiden
long term anticoagulation
inheritance of anti thrombin def
AD
2 key features of anti thrombin def
**buzzwords
highest risk of thrombosis
develop thrombi in unusual places eg splenic / mesenteric arteries
dx of anti thrombin def
anti thrombin assay
ddx of anti thrombin def
protein C/S def
mx of anti thrombin def
long term anti coag - warfarin / argatroban
inheritance of protein c / s def
AD
what are you predisposed to with protein c/s def
VTE (arterial rare)
buzzword association of protein c/s def
warfarin induced skin necrosis
dx of protein c /s def
protein c / s assay
mx of protein c/s def
long term anti coag - argatroban
35F 34 weeks preg has swollen L calf/ preferred anticoag?
LMWH
which of the following in low in preg
- fibrinogen
- factor 7
- protein S
- plasminogen activator inhibitor 1
protein S
pathophysiology of anaemia in preg
volume expansion –> increased cardiac output and dilutional anaemia
what happens to platelet count in preg
thrombocytopaenia
what is HDN
prior sensitisation of Rh- women from prev preg
mediation of HDN
IgG
complications of HDN
foetal anaemia
hydrops fetalis
neonatal jaundice –> kernicterus
how is HDN monitored for
MCA doppler USS
mx of HDN
prevent sensitisation with anti D
IU transfusion
features of HELLP syndrome
anaemia
elevated LFTs
low platelets
blood test features of HELLP
MAHA
raised AST / ALT
low platelets
normal APPT, PT
mx of HELLP
supportive
delivery of foetus
15M with beta thal major has blood transfusion. feels feverish and gets chills shortly after starting. normal obs inc temp. Dx?
non haemolytic transfusion reaction
40M has blood transfusion. within 10 mins, gets fevers, rigors, abdo pain. tachycardia, low BP, fever. Dx?
acute haemolytic transfusion reaction
63M SoB 2 hrs post transfusion. high RR, low BP, low o2 sats, high temp.
O/E bilateral inspiratory creps. Dx?
transfusion related acute lung injury
give the timeline of transfusion reactions
immediate - anaphylaxis
mins to hours - bacterial contamination, ABO incompatability, febrile non haemolytic TR
hours to days - TRALI, transfusion assoicated circulatory overload
days - GvHD, delayed hamolytic transfusion reaction
who is more likely to have anaphylaxis after blood transfusion
**buzzword
IgA deficient people
what mediates ABO incompatibility **buzzword
IgM
with what type of transfusion does bacterial contamination occur most commonly **buzzword
platelet transfusion
what is febrile non haemolytic TR
rise in temp <1 degree without circulatory collapse
cause of febrile non haemolytic TR
release of cytokines by leucocytes
how can febrile non haemolytic TR be prevented
leucodepletion
sx of transfusion assoicated circulatory overload
pulmonary oedema or fluid overload sx over hours
3 signs seen in transfusion associated circulatory overload (TACO)
raised JVP
high PCWP
high BP
(heart failure signs)
sx of TRALI
similar to TACO - fluid overload / pulm oedema sx
cause of TRALI
interaction with HLA ABs in donor blood with recipient
when does TRALI occur
<6 hours post transfusion
key buzzword feature of TRALI
absence of heart failure
TRALI / TACO CXR
bilateral pulmonary infiltrates
mx of TACO
diuretics - furosemide
mediator of delayed haemolytic transfusion reaction
IgG
when does delayed haemolytic TR occur
within 1 week
pc of delayed haemolytic TR
jaundice / splenomegaly few days after transfusion
cause of sx in delayed haemolytic TR
extravascular haemolysis
sx of GvHD
diarrhoea, liver failure
** key one: skin desquamation
BM failure
pathophysiology of GvHD
donor lymphocytes recognsie recipient HLA as foreign
attack gut / liver / skin / BM
prevention of GvHD
irradiating blood components for immunosuppressed recipients
