Haem Flashcards
presentation ALL
CHILDREN lymphadenopathy hepatosplenomegaly pallor ecchymoses or petechiae fatigue dizziness
Ix for ALL
bone marrow aspirate - immunophenotyping
what is ALL
clonal malignancy of lymphoid precursors
what is AML
clonal malignancy of myeloid precursors
presentation AML
ADULTS hepatosplenomegaly pallor ecchymoses or petechiae fatigue dizziness
Auer rods on peripheral blood smear
AML
CD24+ve on immunophenotyping
AML
smudge cells on peripheral blood smear
CLL
presentation CLL
often asymptomatic!!
common myeloid progenitor produces … what two further groups of progenitor cells?
megakaryocyte erythrocyte progenitor
myelocyte progenitor
megakaryocyte erythrocyte progenitor produces what cell types
erythrocytes (RBC) & platelets
myeloid progenitor produces what cell types?
Granulocytes
- neutrophils
- eosinophils
- basophils
Macrophages
common lymphoid progenitor produces what cell types?
B cells
T cells
NK cells
Dendritic cells
RBC lifespan
120d
hormone regulating erythropoiesis
erythropoietin (from the kidneys) - detects reduced O2 and stimulates RBC production in the bone marrow
where does the nucleus of RBCs disintegrate
In the bone marrow
what is a reticulocyte
the earliest RBC in the blood stream - larger and blue appearance due to RNA
structure of Hb
4 globin subunits with a single haem molecule
what is a haem molecule composed of
single Fe2+ ion, surrounded by a porphyrin ring
breakdown products of RBC
amino acids
iron
unconjugated bilirubin (secreted into bile for conjugation in the liver to be excreted)
platelet lifespan
7-10 d
neutrophil appearance on blood film
segmented nucleus
eosinophil appearance on blood film
bi-lobed nucleus
basophil appearance on blood film
large granules that obscure nucleus
monocyte appearance blood film
kidney bean nucleus
lymphocyte appearance blood film
small spherical nucleus
cause of a microcytic anaemia
cytoplasmic defect (Hb is made in the cytoplasm)
therefore there is a problem with haemoglobinisation
lack of availability of:
haem (iron, porphyrin ring) or globin
causes of iron deficiency anaemia
diet deficiency
blood loss
malabsorption
presentation iron deficiency anaemia
fatigue
hair loss
nail changes (koilonychia)
pica (craving non food items)
koilonychia
spoon nails
blood results in iron deficiency
low Hb, low MCV (microcytic anaemia)
low ferritin
low retic count
low transferrin saturation
ferritin
measure of iron storage
Mx iron deficiency anaemia
ferrous fumarate for 3-6m (tds)
s/e of ferrous fumarate
black stools
causes of porphyrin ring synthesis problems
lead poisoning
v rare
causes of globin chain synthesis problems
thalassemia’s (reduced rate of production globin chain)
sickle cell anaemia (abnormal structure of globin chain)
inheritance of thalassaemia
autosomal recessive
HbA
2 alpha chains
2 beta chains
HbA2
2 alpha chains
2 delta chains
HbF
2 alpha chains
2 gamma chains
what forms of Hb are affected in alpha thal
all forms!
all contain alpha
alpha thal trait
1 or 2 genes missing
- carrier state
- no Tx needed
HbH disease (alpha thal)
only one gene left
- mild anaemia
- jaundice
- splenomegaly
Hb Barts hydrops fetalis (alpha thal)
no functional genes
- severe anaemia
- growth retardation
- most die in utero
what forms of Hb are affected in beta thal
only HbA
the only one to contain beta
forms of beta thal
beta thal trait
beta thal intermedia
beta thal major
beta thal trait presentation
asymptomatic
no/mild anaemia
beta thal intermedia presentation
requires occ transfusion
beta thal major presentation
present aged 6-24m (HbF stores have depleted)
failure to thrive
pallor
extramedullary haemopoeisis
Mx beta thal major
regular lifelong transfusions + iron chelation (desferrioxamine)
inheritance of sickle cell anaemia
autosomal recessive
forms of sickle cell anaemia
sickle cell trait
sickle cell anaemia
sickle cell trait presentation
HbAS (one normal beta gene, one abnormal)
- asymptomatic carrier state
- may sickle in severe hypoxia
sickle cell anaemia presentation
HbSS (both beta genes abnormal)
- vascular occlusions and episodes of tissue infarct
Mx sickle cell anaemia
hydroxycarbamide (induces HbF)
penicillin
folic acid
Ix for thalassaemia
HPLC test
cause of a megaloblastic anaemia
nuclear defect - there is a problem with cell division
therefore there is abnormally large nucleated red cell precursors with an immature nucleus.
causes of a megaloblastic anaemia
B12 or folate deficiency
pernicious anaemia
vit B12 deficiency causes - what symp?
neurological problems
where is B12 absorbed
terminal ileum
what does B12 need to bind to for absorption
intrinsic factor (produced by gastric parietal cells)
where is folate absorbed
jejunum
blood film appearance in B12 or folate deficiency
hyper-segmented polymorphs
macro-ovalocytes
Mx B12 deficiency
IM hydroxocolbalamin (3xwk for 2w)
Mx folate deficiency
folic acid 5mg/day for 4m
why should you never give folic acid w/out checking B12 level
can induce subacute degeneration of the spinal cord
what is pernicious anaemia
autoimmune condition -
autoantibodies against gastric parietal cells, therefore no IF produced, therefore no B12 absorption
autoantibodies in pernicious anaemia
anti-intrinsic factor (specific, not sensitive)
anti-gastric parietal cells (sensitive, not specific)
Mx pernicious anaemia
B12 inj for life (hydroxocolbalamin)
causes of a non megalobastic macrocytic anaemia
alcohol
liver disease
marrow failure
hypothyroidism
cause of a false (spurious) macrocytic anaemia
cold agglutinins
haemolysis
when is haemolysis said to have progressed to haemolytic anaemia
when breakdown of RBCs exceeds response!
what are the normal responses to RBC breakdown
reticulocytosis and erythroid hyperplasia
what is extravascular haemolysis
excessive breakdown of RBC at the NORMAL site of destruction (spleen +/- liver)
therefore
you get the NORMAL breakdown products, but in excess:
- unconjugated bilirubinaemia
- urobilogenuria
causes of extravascular haemolysis
hereditary spherocytosis
sickle cell disease
autoimmune haemolysis
inheritance of hereditary spherocytosis
autosomal dominant
pathology of hereditary spherocytosis
RBCs are sphere shaped rather than biconcave disc, causing membrane disruption and destruction by the spleen.
blood film hereditary spherocytosis
spherocytes
Mx hereditary spherocytosis
RBC transfusions + folate replacement
autoimmune haemolysis
warm temperatures = IgG
cold temperatures = IgM
what is intravascular haemolysis
excessive breakdown of RBC within the circulation i.e. ABNORMAL site
therefore you get ABNORMAL breakdown products in excess: - haemoglobinaemia - methylalbuminaemia - haemoglobinuria - haemosiderinuria
causes of intravascular haemolysis
G6PD deficiency
ABO incompatability
DIC
HUS
inheritance of G6PD deficiency
X-linked
pathology of G6PD deficiency
inborn error of metabolism, unable to deal with oxidative stress
blood film G6PD deficiency
Heinz bodies
Mx G6PD deficiency
supportive + folic acid
what does FFP contain
all coagulation factors
what is cryoprecipitate
blood component prepared from FFP
indications for receiving FFP
bleeding
surgery in liver disease with impaired coag
DIC
universal donor
group O
universal recipient
group AB
cause of an immediate haemolytic transfusion reaction
ABO incompatibility
Mx of an immediate haemolytic transfusion reaction
discontinue transfusion, leave line in
flush saline 0.9%
cause of a febrile non-haemolytic transfusion reaction
antibodies are contaminated with white cells
presentation of a febrile non-haemolytic transfusion reaction
0/5 - 1 h after starting transfusion, get shivers and fever
Mx of a febrile non-haemolytic transfusion reaction
slow or stop the transfusion
pcm
Mx of an allergic/urticarial transfusion reaction
slow or stop the transfusion
chlorphenamine 10mg IV
presentation of a delayed haemolytic transfusion reaction
5-10 d after transfusion, low Hb, fever, jaundice
G+S
blood group is established and serum checked for Ab
this is a provision which allows rapid blood delivery in an emergency
crossmatch
testing before a blood transfusion to determine if the donor’s blood is compatible with the blood of the intended recipient
inheritance of hereditary haemochromatosis
autosomal recessive
what gene is affected in hereditary haemochromatosis
HFE gene - affects hepcidin - can’t downregulate ferroportin
pathology of hereditary haemochromatosis
iron is laid down in tissues rather than being stored in ferritin
presentation of hereditary haemochromatosis
"bronze diabetes" - from iron deposition in pancreas weakness fatigue joint pains impotence cirrhosis diabetes cardiomyopathy
Ix hereditary haemochromatosis
- serum transferrin saturation (raised)
2. serum ferritin (acute phase protein so is raised by other conditions, not specific)
Mx hereditary haemochromatosis
venesection (exhaust iron stores)
main cause of secondary iron overload
rptd red cell transfusions
Mx of secondary iron overload
iron chelation Desferioxamine
why is venesection not a Mx option for secondary iron overload
the pts are already anaemic, hence they are receiving transfusions
Mx ALL
chemotherapy - long duration (2-3y)
Mx AML
chemotherapy - intensive cycle
what lineage does hodgkins lymphoma arise from
mature B cells
presentation Hodgkin’s lymphoma
painless lymphadenopathy
itch without rash
alcohol-induced pain
‘B symptoms’ - wt loss, fever, night sweats
Ix hodgkins lymphoma
lymph node biopsy
- Reed Sternberg cells
- Immunohistochemistry (CD 30 +ve)
CD 30 +ve cells on immunohistochemistry
Hodgkin’s lymphoma
reed Sternberg cells
hodgkins lymphoma
Mx Hodgkin’s lymphoma
monoclonal Ab (brentuximab) + chemo
what lineage does non hodgkins lymphoma arise from
90% - B cell lines
presentation non hodgkins lymphoma
B symptoms - night sweats, fever, wt loss
follicular lymphoma gene
non-hodgkins lymphoma -
t(14;18) between the bcl-2 gene
Burkitts lymphoma
non-hodgkins lymphoma -
c-myc gene on (8;14)
CD 20 +ve cells on immunohistochemistry
Burkitt’s lymphoma
Mx non-Hodgkin’s lymphoma
monoclonal Ab (rituximab) + chemo
incurable apart from the early stage
what is hyposplenism
reduced or absent splenic function
causes of hyposplenism
congenital absence surgical removal trauma immune infarction (sickle cell) infiltration (lymphoma, amyloid) drugs (methyldopa, chemo)
blood film hyposplenism
Howell Jolly bodies
(inclusion of nuclear chromatin remnants)
infection prophylaxis in hyposplenism
pneumoccal + HiB vaccines
long term oral penicillin
what is hypersplenism
enhanced filtration, pathological pooling or shortening of RBC lifespan
causes of hypersplenism
cirrhosis
lymphoma
TB
CTDs and inflammatory disease
presentation of pancytopenia
anaemia - fatigue, SOB, CVS compromise
neutropenia - infection
thrombocytopenia - bleeding
congenital cause of bone marrow failure
Fanconi’s anaemia
inheritance of fanconis anaemia
autosomal recessive
presentation fanconi’s anaemia
short stature
hyperpigmentation
skeletal abnormalities
increase in solid tumours + leukaemia
acquired causes of primary bone marrow failure
aplastic anaemia
myelodysplastic syndromes
what is aplastic anaemia
autoimmune attack against the haemopoietic stem cell
bone marrow appearance aplastic anaemia
hypocellular
what are myelodysplastic syndromes
a group of cancers, where there is apoptosis of the mature cells
bone marrow appearance myelodysplastic syndromes
hypercellular - lots of immature cells due to ineffective erythropoiesis
causes of secondary bone marrow failure
drugs - chemo, chloramphenicol, alcohol
B12/folate deficiency
lymphoma
HIV
what is multiple myeloma
cancer of plasma cells
the presence of ?-? characterizes multiple myeloma?
IgG monoclonal antibody (paraprotein)
presentation multiple myeloma
Direct tumour effects:
- bone lesions (punched out lytic lesions)
- hypercalcaemia
- bone pain
- marrow failure
Paraprotein effects:
- renal cast nephopathy
- immune suppression
- hyper viscosity
- amyloid
Ix multiple myeloma
serum/urine electrophoresis - bence jones proteins
bence jones proteins
serum/urine electrophoresis
- multiple myeloma
RBC appearance multiple myeloma
roleaux formation
monoclonal gammopathy of uncertain significance (MGUS)
high paraprotein (<30g/L) NO clinical features of myeloma
waldenstrom’s macroglobulinaemia
clonal disorder of intermediate cells between a lymphocyte and plasma cell
paraprotein in waldenstrom’s macroglobulinaemia
IgM
what is amyloidosis
mutation in the light chain of plasma,
leads to accumulation of the mutated protein in tissues - eventual organ failure & death
Ix amyloidosis
organ biopsy
- Congo red stain with apple green birefringence under green light
what is CML
a myeloproliferative disorder
clonal malignancy of myeloid precursors
important mutation in CML
Philadelphia chromosome (9;22) translocation
BCR-ABL +ve
presentation CML
splenomegaly
wt loss
excessive sweating
gout (due to purine breakdown)
Mx CML
tyrosine-kinase inhibitor (imatinib)
what is polycythaemia
a myeloproliferative disorder
a true increase in red cell mass
causes of primary polycythaemia
polycythaemia rubra vera
JAK 2 mutation
polycythaemia rubra vera
causes of a secondary polycythaemia
smoking
COPD
altitude
causes of a pseudo polycythaemia
dehydration
obesity
diuretic therapy
presentation of polycythaemia
aquagenic pruritus
thrombosis
gout
Mx polycythaemia rubra vera
hydroxycarbamide + aspirin
what is essential thrombocythemia
a myeloproliferative disorder
a true increase in platelets
Mx essential thrombocythaemia
if plt < 1500 x 10^9/L and no prev thrombosis - no Tx
low risk of thrombosis - aspirin
high risk of thrombosis - hydroxycarbamide
what is myelofibrosis
reactive + reversible process
abnormal production of all 3 lineages due to marrow scarring
- therefore there is extramedullary haemopoiesis
presentation myelofibrosis
massive splenomegaly
blood film appearance myelofibrosis
leucoerythroblastic cells
teardrop RBCs
Mx myelofibrosis
stem cell transplant
what is responsible for primary haemostasis
platelets
process of primary haemostasis
vessel wall damage
release of vWF from vessel wall
platelets have receptors to vWF
screening test for primary haemostasis
platelet count
what is responsible for secondary haemostasis
coagulation cascade
explain process of coagulation cascade
INTRINSIC PATHWAY:
Tissue Factor (III) is released from damaged vessels.
Activates Factor VII (VIIa).
Activates Factors V and X (Va & Xa).
Activates prothrombin (II) to thrombin (IIa).
Activates fibrinogen (I) to fibrin (Ia).
EXTRINSIC PATHWAY:
Factors VIII and IX are activated (VIIIa & IXa).
Potentiates the activation of Va and Xa even more.
screening test for the intrinsic coagulation pathway
prothrombin time (PT)
screening test for the extrinsic coagulation pathway
activated partial thromboplastin time (aPTT)
connection between vWF and Factor VIII
vWF has a role in binding to Factor VIII and protecting it
what is responsible for the breakdown of fibrin clots
plasmin
(plasminogen produced by the liver,
converted to plasmin by tissue plasminogen activator)
natural anticoagulants
anti thrombin
protein c and protein S
role of anti thrombin
inhibits thrombin (IIa) and Factor Xa
role of protein c and protein s
inhibits Factor Va and Factor VIIIa
what activates protein c and protein s
the presence of thrombin
disorders of primary haemostasis
VASCULAR PROBLEMS
- inherited (marfans)
- acquired (HSP)
PLATELET PROBLEMS
- reduced number (thrombocytopenia)
- reduced function (renal failure, nsaids, aspirin)
VON WILLEBRAND’S DISEASE
inheritance of von willebrands
autosomal dominant
presentation von willebrands
bruising
epistaxis
menorrhagia
increased bleeding post-tooth extraction
Ix for von willebrands
APTT - prolonged
factor VIII has a protective factor on VIII
causes of a prolonged APTT and PT
multiple clotting factor deficiency
liver failure, vit K deficiency, DIC
inheritance of haemophilia
x-linked
haemophilia A
factor VIII deficiency
haemophilia B
factor IX deficiency
presentation haemophilia
recurrent haemarthroses
recurrent soft tissue bleeds
factor V leiden disease
inherited thrombophilia
point mutation in Factor V, so protein C can’t inhibit it
anti phospholipid syndrome predisposes to what type of thrombosis?
both arterial and venous !
heparin mode of action
potentiates anti-thrombin
monitoring heparin
LMWH - anti Xa levels
unfractionated heparin - APTT
Mx bleeding on heparin
stop heparin (has a short half life)
if bleeding severe - protamine sulphate
mode of action of rivaroxaban
factor Xa inhibitor
mode of action of apixaban
factor Xa inhibitor
mode of action of dabigatran
direct thrombin inhibitor
mode of act ion of warfarin
antagonizes vitamin K
why does warfarin have a prothrombotic effect in the first few days
inhibits protein C
monitoring warfarin
PT
Mx bleeding on warfarin
stop warfarin
give Vit K (takes 6h to work)
give prothrombin complex concentrates (works immediately)
aspirin mode of action
inhibit the COX pathway
- COX is needed to make thromboxane A2, which is released from platelets when they aggregate.
s/e of aspirin
bleeding
blockage of prostaglandins - ulceration, bronchospasm
mode of action of clopidogrel
ADP receptor antagonist
mode of action of dipyradimole
phosphodiesterase inhibitor
equations to work out cause of shock
MAP = CO x TPR
CO = HR x SV
