week 12 Flashcards
what are two tissue factors which aid in platelet adhesion when BVs get damaged
subendothelial collagen
von willebrand factor
process of platelet adhesion to damaged blood vessles 4
exposed extracellular matrix including subendothelial collagen and von willebrand factor
platelets bind
binding triggers platelet activation resulting in a shape change and granule secretion
glyocprotein IIb/IIIa receptors on platelets bind irreversibly to fibrinogen
role of glycoprotein IIb/IIIa
it is activated by platelet activation and allows the irreversible binidng of platelets to fibrinogen
role of ADP in platelet adhesion
secreted by activated platelets activating other platelets
role of thromboxane in platelet adhesion
diffuses out of activated platelets activating more platelets
what are the four different mechanisms of actions in antiplatelets
COX inhibitors
ADP receptor antagonists
Phosphodiesterase inhibitors
GPIIb/IIIA
mechanism of COX inhibitors
inhibits COX1 enzyme used to produce thromboxane
therefore reduces platelet activation
mechanisms of ADP receptor antagonists
prevents ADP binding to platelets
mechanism of GPIIb/IIA inhibitors
prevents activation og GPIIB/IIIA receptors preventing platelet adhesion to fibrinogen
mechanism of phosphodiesterase inhibitors
inhibit platelet activation but mechanism unknown
intrinsic pathway of blood coagulation
activation of mulitple factors which leads to the activation of factor x
extrinsic pathway of coagulation
tissue factor which along with factor 7 activates factor 10
common pathway steps 5
factor 10 converted to factor 5
causes activation of factor 2 (prothrombin to thrombin)
thrombin (akak actiavted factor 2) turns factor one into its active form (fibrinogen to fibrin)
fibrin laid on pleatlet plug
stabilised with factor 13 whcih is fibrin stabilising factor
what is factor 2
prothrombin
what is factor 1
fibrinogen
what is factor 13
fibrin stabilising factor
what triggers activation of coagulation 2
breach in endothelium
foreign surfaces
process of fibrinolysis 3 steps
tissue plasminogen factor released
converts plasminogen into its active form plasmin
breaks down the fibrin
tranexamic acid function and mech
inhibits fibrinolysis
it is a competitive inhibitor which binds to plasminogen preventing it from converting to plasmin and binding to fibrin to initiate fibrinolysis
types of anticoagulants 5:
antithrombin
protein c
vitamin k anatgonsits
factor 10 inhibitors
direct oral anticoagulants
how does activated protein C cause anticoagulation 3
inhibits clotting factors and prothrombinase
produced when thrombin is produced
acts in a negative feedback loop to keep thrombin levels in check
how does activated antithrombin cause anticoagulation
neutralises clotting factors
how does vitamin k anatagonists cause anticoagulation 3
they inhibit clotting factors which are dependent on vitamin k for synthesis
which clotting factors are affected by vitamin k anatagonists
2, 7, 9 and 10
what are the three components of virchow’s triad
hypercoaguability
blood stasis
vascular damage
how does pregnancy cause hyperocoagulability
to prevent blood loss there are multiple coagulant mechanisms including:
- decreased venous blood flow
- increased clotting factors
- increased protein c resistance
-incr inhibitors of fibrinolysis
how does hormone replacement therapy increase coagulation
increases fibrinogen and some clotting factors
how does advanced carnioma cause increased coagulation 2ways
venous stasis due to tumour compression
some tumours can express tissue factor which activates the extrinsic coagulation pathway
heriditary thrombophilic conditions 3
factor 5 leiden mutation
activated protein c resistance
antithrombin deficiency
risk factors of coagulopathies 4
male
old age
obesity
previous venous thrombotic event
how can a DVT lead to a PE (define PE)
PE is an embolism which reaches pulmonary ciruclation and then gets occluded
DVT can dislodge becoming an embolus and then reach pulmonary circulation to become a PE
what is prothrombin time
this is part of an investigatve test which measures how long blood takes to clot
it is presented as an INR
investigations in diagnosis of coagulopathies 10
- prothrombin time
- activated partial thromboplastin time
- fibrinogen level
- thrombin time
- CBE
- genetic testing
- antithrombin activity
- protein c activity
- blood film
- VWD and factor 8
what is activated partial thromboplastin time
evaluates the clotting function of the intrinsic pathway
thrombin time
ability for blood to form a fibrin clot by measuring the time after thrombin addition
clinical feature of a venous thrombosis 5
unilateral chest pain due to inflammation
peripheral oedema = due to increased fluid
erythema due to increased blood flow
tenderness due to inflammation
rubor due to warmth
clinical features of a pulmonary embolism 5
dyspnoea
pleuritic chest pain
tachycardia
haemoptysis
syncope
different components of blood avaiable for transfusion 4
red cell
platelets
plasma
cryoprecipitate
fractionated blood products 3
immunoglobulins
albumin
clotting factors
what is cryprecipitate
supernatant from lightly thawed fresh frozen plasma
what are the mandatory testings required when someone donates their blood 4
ABO and RHD blood group
red cell antibody screening
syphillis screening
viral screening
what is rhesus blood typing and what does an incompatability mean?
Routine rhesus typing is done to test for the absence or presnece of D antigen
RHD + means present
RHD - means absent
complications of a blood transfusion 6
haemolytic reaction
allergic reaction
infection transmission
iron overload
volume overload
febrile non haemolytic reaction
what are the three pillars of patient blood management
optimising haemoglobin
minimising blood loss
appropriate transfusion
what happens as a result of volume overload in an iron transfusion 2
too much fluid too quickly resulting in:
- congestive heart failure
- pulmonary oedema
what is febrile non maermolytic reaction in blood transfusion complication
immune response to the white blood cells in the transfused blood
what is primary haemostasis bleeding disorder (give three examples)
platelet disorders affected the platelet plug formation including
thrombocytopenia
platelet dysfunction
von Willebrand factor deficiency
what is secondary haemostasis bleeding disorder (give two examples)
affects the fibrin mesh formation and clotting cascade
heriditary = haemophilia
medication induced
what is increased clot degredation bleeding disorder (2)
hyperfibrinolysis
causes include:
hereditary
prostate cancer
causes of acquired bleeding disorders 7
cancer
disseminated intravasuclar coagulation
drug related
thrombocytopenia
immune thrombocytopenia purpura
renal failure
myeloma and lymphoma
how does disseminated intravascular coagulation work 2
characterised by systemic coagulation activation causing:
- fibrin clots formation
- consumption of platelets and coag factors
how does immune thrombocytopenia purpura work
autoimmune disorder characterised by igG antibodies which destroy platelets
inherited bleeding disorders 3
von willebrand disease
haemophilia a and b
what is the most common bleeding disorder
von willebrand disease
what is haemophilia a deficiency of
factor 8
what is haemophilia b a deficiency of
factor 9
clinical features with bleeding disorders 6
bruising
purpura
bleeding post surgery
menorrhagia
haematuria
epistaxis
what are the two functions of von willebrand factor
platelet adhesion
prevention of factor 8 degredation
anticoagulants 5
heparins
vitamin k antagonists
DOACs: apixaban, rivaoxaban
Dabigatran
example of thrombolytic agent
tPA (tissue plasminogen activator) catalyses plasminogen conversion to plasmin increasing fibrinolysis
what is factor replacement therapy and what three are done
re-supply clotting factors to prevent/treat haemorrhage/internal bleeding
the three diseases treated are:
vWF deficiency
haemophilia a
haemophilia b
contraindications generally for anticoagulants and antiplatelets 3
active/recent haemorrhage
recent surgery
severe thrombocytopenia
complications of oral antiplatelets (2 examples of these drugs)
ex. aspirin, tricagrelor
bleeding, Gi ulceration
unfractionated heparin characteristics 6
administered intravenously
fully reversible
independent of renal failure
more complex dosage
requires frequent monitoring
high risk of HITS
Low molecular weight heparin 3
subcutaneous injection
partially reversible
longer half life
side effects of heparins 4
bleeding
Heparin induced thrombocytopenia syndrome = HITS
alopecia
osteoporosis
what are the two types of ways that one can give heparin in terms of aim of procedure
prophylactic: prevention of VTE
therapeutic: treatment of VTE
warfarin when is it used 2
in severe kidney disease and in patients with a mechanical heart valve
side effects of warfarin 4
high drug interactions
high bleeding risks
alopecia
liver dysfunction
to whom do we not give warfarin to
when pregnant
key DOACS
apixaban and rivaroxaban
limitation of DOACs 3
cant give to pregnant
cant give in severe renal failure
no reversal mechanisms
benefits of DOACs
few drug interactions
simple dosages
low bleeding risk
desmopressin
releases endothelial stored coagulation factors including:
von willebrand factor
factor 8
heparin function 3
activates antithrombin
inhibits factor ten
inhibits thrombin
what are the tests to do in coagulopathies 11
vWF and subendoethlila collagen tests
CBE
Blood film
Prothrombin time
activated partial thromboplastin time
Thrombin time
Fibrinogen level
antibody testing
genetic testing
protein c activity
what are 3 thrombophilic conditions
factor V leiden mutation
active protein c resistance
antithrombin deficiency
