Haematology Flashcards
Donation order of blood products
O can donate to A, B and AB
A and B can donate to AB
AB can only donate to AB
What are duffy antibodies and what pathology is associated
antibody which is negative on antibody testing but can cause haemolytic transfusion reactions
site of entry for plasmodium vivax into RBCs
What does FFP contain and what is used for
coagulation factors
used in coagulopathies
what does cryoprecipitate contain
Fibrinogen
factor 8, vWF, factor 13
used in critical bleeding, trauma, DIC, big procedures
Platelets orignate from
magakaryocytes
macrophages originate from
monocytes
What does hypersegmented neutrophils indicate
B12/folate deficiency
Receptors present on platelets
Gp1b for vWF receptor
Gp11b/111a receptor for fibriniogen
Platelet proliferation stimulated by
thrombopoeitin stimulates magakaryocyte proliferation
What are macrophages activated by
IFN gamma
Most important commponent of granuloma
macrophages fuse to form giant cells
Causes of eosinophilia
PACMAN Eats
Parasites
Asthma
Chronic adrenal insufficiency
Myeloproliferative disorders
Allergic processes
Neoplasm (hodgkins)
Eosinophilic granulomatosis with polyangitis
Causes of basophilia
myeloproliferative (esp CML)
Causes of IgE independent mast cell degranulation
Vancomycin, opioids and contrast
What is mastocytosis
rare proliferation of mast cells in skin and organs
associated with c-KIT mutations and raised serum tryptase
high histamine causes flushing, pruritis, hypotension, abdo pain, diarrhoea and peptic ulcer disease
NK cell surface receptors
CD56 and CD16
Nk cell function
induces apoptosis in those not espressing MHC1
B cell surface receptors
CD19, CD20, CD21
T cell surface receptors
both have CD3
CD8 (cytotoxic)
CD4 (helper)
DAT positive if
AIHA
Platelet plug formation process
injury -> vWF binds to exposed collagen -> platelets bind to vWF via Gp1b -> platelets release ADP binds to PY12 receptor and induces Gp11b/111a on surface of platelets -> more plalets bind to Gp11b/111a and link platelets
Mechanism of aspirin
irreversibly inhibits COX which inhibits TXA2 synthesis (pro-aggregation of platelets)
MoA for clopidogrel, ticagrelor and prasugrel
inhibit ADP binding to P2Y12 receptor, blocks expression of G11b/111a
Tirofiban and eptifibatide MoA
inhibit Gp11b/111a directly
Desmopressin effect on coagulation
promotes release of vWF and factor 8
What is in extrinsic pathway
VII to VII and tissue factor complex
Intrinsic pathway process
Tissue damage activates factor XII -> leads to downstream formation of IXa/VIIIa complex formation (to help process X to Xa)
How does C1 esterase inhibitor affect coagulation
inhibits XIIa and XIa in the intrinsic pathway
What is the function of protein C and S
inhibits IXa/VIIIa complex and inhibits prothrombinase (Va/Xa)
Stops coagulation cascade
Function of heparin, LMWH, dabigatran
direct thrombin (IIa) inhibitors (stop conversion of fibrinogen to fibrin)
Process how clots are broken down
cleaved by plasmin
plasminogen converted to plasmin by tPA (synthestic tPA tenectaplase, alteplase)
tPA blocked by transexamic acid
MoA transexamic acid
blocks tPA from processing plasminogen to plasmin
Vit K dependent factors
2, 7, 9, 10, protein C and S
Haemophilia A is def of
factor 8
x-linked recessive
Haemophilia B is def of
factor 9
x-linked recessive
haemophilia C is def of
factor 11
autosomal recessive
C1 esterase function
inhibits kallikrein which activates bradykinin
C1 esterase def -> hereditary angioedema
MoA antithrombin
mainly inhibits thrombin (IIa) and Xa
heparin enhances activity of antithrombin
Mechanism of factor V leiden mutation
produces factor V resistant to inhibition by activated protein C
increases clotting
Warfarin MoA
inhibits vit K epoxide reductase so Vit K cannot be activated
spur cells assoc
liver disease
vit E def
abetalipoproteinaemia
burr cells assoc
liver disease
ESRD
pyruvate kinase def
teardrop cells assoc
bone marrow infiltration
schistocytes association
MAHAs (DIP, TTP/HUS, HELLP) and mechanical haemolysis (valves)
bite cells assoc
G6PD deficiency
Spherocytes assoc
AIHA
hereditary spherocytosis
elliptocytes assoc
hereditary elliptocytosis - mutation in gene encoding for RBC membrane
target cells assoc
HbC disease
asplenia
liver disease
thalassemia
sickle cell crisis occurs when
low O2 conditions (high altitude, acidosis)
high HbS concentration (dehydration)
Howell-Jolly bodies assoc
functional hyposplenism (sickle)
asplenia
basophilic stippling assoc
sideroblastic anaemia
thalassemias
pappenheimer bodies assoc
siderblastic anaemia
heinz bodies assoc
G6pd deficiency
Causes of microcytic anaemia
TAIL
thalassemias
Anaemia of chronic disease
Irion def
Lead poisening
How to tell between intrinsic and extrinsic haemolytic anaemia
instrinsic - low hapto
extrinsic - +ve DAT
Causes of intrinsic haemolysis
Membrane defects - hereditary spherocytosis, PNH
Enzyme deficiencies - G6PD def, pyruvate kinase def
Haemoglobinopathies - sickle cell, HbC
Causes of extrinsic haemolysis
autoimmune
microangiopathic
macroangiopathic
infections
Difference between megaloblastic and non-megaloblastic anaemia
both MCV >100
Megaloblastic has DNA affected -> B12 def, orotic anaemia, fanconi anaemia
non - alcohol use, liver disease
Iron studies in iron def
low iron, low ferritin, low transferrin satn, high transferrin
iron studies in anaemia of chronic disease
low iron, high ferritin, low transferrin, low/normal transferrin satn
Iron studies in pregnancy/OCP use
high transferrin
How is iron absorbed
Iron is reduced to Fe2+ by DCYTB before it is absorbed by DMT1. Then bound to ferritin and moved out of cell by feroportin
Role of hepcidin
binds and internalises ferroprotin
decreases iron absorption
What regulates hepcidin
hepcidin decreased in iron deficiency, hypoxia, non-ferroportin mutations of haemochromotosis (HFE, TFR2, HAMP and HJV)
Hepcidin increased in inflammatory states, iron overload, feroportin mutated haemochromatosis
Signs of iron def
anaemia sx
koilonychia
pica
glossitis, cheilosis
Plummer-vinson sydrome
What is Plummer-vinson syndrome
iron def, esophageal webs and dysphagia
Population alpha thalassemia most prevalent
asian and african
alpha thalassemia what on peripheral smear
target cells
degrees of alpha thalassemia
Hb barts - 4 deletions, dead
HbH disease - 3 deletions, severe anaemia’
alpha thalassemia minor - 2 deletions, mild anaemia
alpha thalassemia minima - siletn carrier
population common in beta thalassemia
mediterraneans
Degree of beta thalassemia
beta thalassemia major - 2 absent Beta globin chains, severe anaemia, skeletal deformities, extramedullary haemotopoesis (heptosplenomegaly)
beta thalassemia intimedia - 1 absent or reduced beta globin chain with another reduced chain, variable anaemia
beta thalassemia minor - one chain reduced beta globin, mild anaemia, raised HbA2 >3.5%
What is luspatercept
for treatment of thalassemia, modified form of actin receptor IIb, binds TGF-beta ligands and increases differenciation and proliferation of erythroid precursors
how does lead poisening cause microcytic anaemia
inhibits ferrochelatase and ALA dehydrogrenase -> reduced heme synthesis
sx of lead poisening
lead lines on gingivae and metaphysis of bones
encephalopathy
erythrocyte basophilic stippling
abdo colic
sideroblastic anaemia
wrist and foot drops
treatment of lead poisening
chelation with succimer or EDTA
Causes of sideroblastic anaemia
genetic - x-linked defect in ALA synthase gene
acquired - myelodysplasic syndromes
reversible - alcohol, lead poisening, B6 def, copper def, drugs
where is B12 absorbed
terminal ileum
difference between folate and B12 def
folate doesn’t have neurological sx
folate has raised homocysteine but normal methylmalonic acic
B12 has cord degen and raised both homocysteine and methylmalonic acid
Associations of HLA DR5
pernicious anaemia and hashimoto’s
Lab indications of haemolysis
high LDH, reticulocytosis, unconjugated bili, pigmented gallstones, urobilinogen in the urine
Ix findings of intravascular haemolysis
low haptoglobin, schistocytes on smear
haemoglobin in urine
urinary haemosiderins
urobilinogen in urine
Causes of intravascular haemolysis
mechanical (prosthetic valve)
PNH
MAHAs
How does extravascular haemolysis occur
RBCs destroyed by macrophages in spleen -> unconjugated bili -> conjugated in liver -> urobilinogen to bowel, readbsorbed and process in liver to be excreted in urine
Ix findings in extravascular haemolysis
splenomegaly
spherocytes in smear
no Hb or haemosiderin in urine
can have urobilinogen in urine
Main mechanism of anaemia of chronic disease
inflammation raised IL6 which increases hepcidin which internalises ferroprotin and reduces iron absorption from gut
aplastic anaemia causes
radiation
viral
fanconi anaemia
idiopathic
drugs
which viruses cause aplastic anaemia
EBV, HIV, hepatitis
which drugs cause apastic anaemia
cholamphenicol
alkylating agents
antimetabolites
Cause of fanconi anaemia
Autosomal recessive DNA repair defect leading to bone marrow failure
Clinical features of fanconi anaemia
short stature
cafe au lait spots
thumb/radial defects
predisposition to malignancy
Ix findings of aplastic anaemia
low reticulocytes
elevated EPO
aplastic anaemia vs aplastic crisis
aplastic anaemia has pancytopenia whereas crisis has anaemia only
Sx of aplastic anaemia
those related to anaemia - fatigue, malaiase, pallor
thrombocytopenia - purpura, mucosal bleeding, petechiae
leukopenia - infection
Causes of intrinsic haemolysis
Hereditary spherocytosis
PNH
Pyruvate kinase deficiency
sickle cell
HbC disease
G6PD
Underlying pathology of hereditary spherocytosis
autosomal dominant
defect in proteins interacting with RBC skeleton
premature removal by spleen
EXTRAVASCULAR haemolysis
Sx of hereditary spheocytosis
splenomegaly
pigmented gallstones
aplastic crisis secondary to parvovirus
How to diagnose hereditary spherocytosis
decreased fluorescence of RBCs on EMA binding test
increased fragilty in osmotic fragility test
Treatment for hereditary spherocytosis
splenectomy
Pathology of PNH
haematopoetic stem cell mutation -> increased complement mediated intravascular haemolysis
loss of CD55 and CD59 which protect RBC from complement
occurs at night due to mild resp aciodosis when breathig slowly in sleep
Triad of PNH
DAT -ve (because intravascular haemolysis is -ve)
pancytopenia
venous thrombosis
sx of PNH
smooth muscle dystonias - dysphagia, abdo pain
pink/red morning urine
pancytopenia
venous thrombosis
Pulmonary HTN (decreased NO)
PNH associations
CML, aplastic anaemias
PNH dx
absence of CD55/59 on flow cytometry
PNH treatment
ravulizumab/eculizumab (targets C5 -> terminal complement)
- higher risk of meningitis from neisseria, needs abx prophylaxis (penicillin)
if bone marrow failure - allogenic stem cell transplant
G6PD pathology
x-linked recessive
G6PD defect -> reduced NADPH -> reduced glutathione -> increased RBC susceptibility to oxidative stress -> hameolysis to sulfa, antimalarials and fava beans
Intra and extravascular haemolysis
smear fings for G6PD def
heinz bodies and bite cells
pyruvate kinase deficiency pathology
smear findings
Autosomal recessive
pyruvate kinase defect -> reduced ATP -> rigid RBCs -> extravascular haemolysis
smear: burr cells
Sickle cell anaemia pathology
point mutation in Beta globin gene -> single AA substitution -> alters hydrophobic region of RBC, aggregation of Hb
intra and extravascular haemolysis
Low O2, high altitude or acidosis precipitates sickling -> vasoocclusive disease