general Flashcards
haemophilia A and B transmission
X-Linked
risk of inheriting haemophilia A
1/10,000
risk of inheriting haemophilia B
1/60,000
haemophilia complications
viral infections, anti Factor 8 antibodies, MI with DDAVP
epidemiology of von Willebrand disease
1/200
transmission of Von Willebrand disease
autosomal
type 1 von Willebrand disease refers too
quantitative deficiency
type 3 von Willebrand disease refers too
complete deficiency
3 examples of acquired bleeding disorders
liver failure, renal failure, warfarin
Ecchymosis refers too
bruise
ABO gene encodes for
glycosyltransferase
A and B genes code for
transferase enzymes
A antigen is
N-acetyl-galactosamine
B antigen is
galactose
out of A, B and O which is recessive and which is dominant?
A-B co dominant, O recessive
blood donors screened for
Hep B, C, E, HIV, syphilis
1 unit of RBC’s =
5g/L
RBC’s transfusion time
2-4 hours
shelf life of platelets
7 days
Fresh frozen plasma for a bleeding patient with factor 8 or 10 deficiency
no concentrate is available
Fresh frozen plasma for a bleeding patient on warfarin
no concentrate and Vit K
bleeding patient on DOAC use fresh frozen platelets?
no
a patient with DIC use fresh frozen platelets?
no
bleeding patient with DIC use fresh frozen platelets?
yes
patient with massive haemorrhage but no coagulation results use fresh frozen platelets?
yes
hypotensive patient with low albumin use fresh frozen platelets?
no
epitope spreading refers too
breakdown of self tolerance, the resulting inflammation releases further self peptides and thus more inflammation
if the AIRE gene is mutated what kind of tolerance can’t take place?
central
AIRE gene refers too
Autoimmune Regulator
peak onset for an autoimmune disease is
15-65 years
M or F for autoimmune diseases
F
percentage of the population with an autoimmune disease?
3%
molecules that enable laminar blood flow
heparin, TFPI, thrombomodulin, NO, prostacyclin
platelet cell surface receptors are for
ADP, epinephrine, thrombin
platelet alpha granule releases
VWF and thrombin
dense platelet granule releases
ADP, calcium, serotonin
clopidogrel works on the
ADP receptor
extrinsic pathway for clotting
Factor 7 and Tissue factor to factor 10-> prothrombin->thrombin which cleaves fibrinogen to fibrin
intrinsic pathway for clotting is
factor 11->9->8->10-> PT-> loads of thrombin = loads of fibrin
natural anticoagulants
protein C and S, anti-thrombin, tissue factor pathway inhibitor
Abciximab pathway of anticoagulation
GP IIb/IIIa
warfarin pathway of anticoagulation
9, 7, 10, prothrombin
Vit k dependent factors of coagulation
9, 7, 10
heparin mechanism of anticoagulation
10 and thrombin
Rivaroxaban mechanism of anticoagulation
ten
haematological malignancy M or F
M
haptens are
small molecule irritants that bind to proteins to elleicit an immune response
most common cause of an allergen is
peanut
percentage of the population effected by allergies
40%
polymorphism of what gene is responsible for eczema
filaggrin
role of Mannan binding Lectin is
a collagen-like protein that binds sugars in bacterial cell walls and activates the classic complement pathway
for gene therapy to be successful what criteria must be met?
evidence correcting mutation will improve condition, transfected gene will confer survival advantage and no cause malignancy
immunodeficiency presents as SPUR
serious, persistent, unseals and recurrent infections
MHC 2 is essential for
CD4+ T cell receptor
MHC class 1 for essential for
CD8 T cells
NK cells produce what for recruitment
IFN - gamma which stimulates macrophages, TH1 and CD8 cytotoxic T cells
NK cells release what for apoptosis
perforin and granzyme
which Ab is a pentamer
IgM
which Ab is a dimer
IgA
lectin, classical and alternative pathways all activate which complement protein?
C3
C3 activating C3b leads too
membrane attack complex and opsonin
C3 activating C3a leads too
inflammation
membrane attack complex pathway
C3->C3b->C5->C5b->6,7,8,9,9,9,9 -> membrane attack complex
complement proteins for chemotaxis are
C3a, C5a
complement proteins for opsonisation are
C3b, C4b
maintain solubility of Ab complexes complement proteins
C3b, C4b, C2
examples of direct immunotherapy
monoclonal Ab, CARS, Bi-specific
examples of indirect immunotherapy
tumour and dendritic cell vaccines, adoptive cell transfer, cytokine therapies, checkpoint inhibitor therapies, stimulatory antibodies
hybridoma consists of
myeloma cell and the spleen cells from a mouse immunised with known antigen
Fc portion of an antibody is defined by
the heavy chains
5 types of heavy chain are
IgG IgA Mu IgM IgD epsilon IgE
most prevalent antibody subclass is
IgG
light chains are either
Kappa or Lambda random selection for each cell
Fab region of an antibody is
variable, defines bidnign
IgG total levels
6-15g/L
IgA total levels
1-4.5G/L
IgM total levels
0.5-2.0g/L
peak for myeloma
7th decade
myeloma CRAB
hypercalcaemia, Renal failure, anaemia, Bone disease
what percentage of bone marrow must be plasma cell for it to be myeloma
10%
high risk neutropenia
<0.2x10*9/l
significant risk neutropenia
<0.5x10*9/l
time frame for high risk neutropenia
> 7 days
additional risk factors for infection
disrupted skin, altered flora, lymphopenia, monocytopenia
percentage of febrile neutropenia caused by gram positive bacteria
60-70%
percentage of febrile neutropenia caused by gram negative bacteria
30-40%
percentage of blasts in a bone biopsy of acute myeloblastic leukaemia
> 20% blasts of marrow cells
acute promyelocytic leukaemia use of
all-trans retinoic acid and arsenic trioxide
mode of action for a TKI inhibitor of BCR-ABL in chronic myelocytic leukaemia
imatinib blocks the ATP of BRC-ABL preventing the phosphorylation of tyrosine
percentage of JAK2 mutations in polycythaemia Vera
95%
acute lymphoblastic leukaemia most likely to occur in
children <6 years (75%)
CD34, TDT are markers of what?
early immature cells
CAR stands for
chimeric antigen receptor
acute lymphoblastic leukaemia poor risk factors
T(9;22), slow response, increased WCC, increasing age
chronic lymphocytic lymphoma stage A
<3 lymph node areas
chronic lymphocytic lymphoma stage B
3 or more lymph node areas (8yr survival)
chronic lymphocytic lymphoma stage C
anaemia and B symptoms or thrombocytopenia (6yrs)
indications for treatment for chronic lymphocytic lymphoma
massive lymphadenopathy, splenomegaly, progressive marrow failure, lymphocyte doubling time <6 months, systemic symptoms
commonest subtype of lymphoma
Diffuse large B Cell lymphoma a
diffuse large B cell lymphoma high grade or low grade
high grade
follicular lymphoma high grade or low grade?
low
Hodgkin lymphoma is associated with
EBV
hodgkin lymphoma constitutes what percentage of all lymphomas?
30%
total body iron in approx.
4g
iron is absorbed in the
duodenum
immune haemolysis warm autoantibody causes
autoimmune, drugs, CLL
immune haemolysis cold autoantibody causes
CHAD, infections, lymphoma
immune haemolysis alloantibody causes
transfusion reaction
intrinsic factor is secreted by
parietal cells
B12 and intrinsic factor is absorbed In the
distal ileum
other causes of microcytosis
alcohol, drugs, disordered liver function, hypothyroidism, myelodysplasia
metals req. for RBC production
iron, copper, cobalt, manganese
vitamins req. for RBC production
B12, folic acid, thiamine, Vit B6, amino acids
hormones required for RBC production
erythropoietin, GM CSF, androgens, thyroxine, SCF
G6PD transmission
X linked
hair on end X-ray appearance indicates
Beta thalassaemia major
Haemophilia A is a deficiency in which factor?
8
haemophilia B is a deficiency in which factor?
9
APTT measures which coagulation pathway?
intrinsic
PT measures which coagulation pathway
extrinsic
mother tells you father also have haemophilia (obligate carriers), chances of any other children having haemophilia;
1/4 chance
will DDAVP work in severe haemophilia?
no only in mild
normal platelet account is around
140-400
