Blood clotting Flashcards
normal intact endothelium is what kind of surface
antithrombotic
two potent vasodilators and inhibitors of platelet function produced by endothelium
prostacyclin, nitric oxide
after vascular injury there is vaso-
constriction
vasoconstriction after vascular injury is partly mediated by which two platelet activation products
serotonin and thromboxane A2
after vascular injury, blood flow is exposed to (2)
subendothelial collagen and tissue factor
subendothelial collagen activates
intrinsic pathway of blood coagulation
tissue factor activates
extrinsic pathway of blood coagulation
exposure to collagen activates intrinsic pathway and stimulates
platelet activation
platelets bind to collagen via
von willebrand factor (vWF)
von willebrand factor is released from
endothelial cells
von willebrand factor binds to collagen fibres and platelets via
platelet membrane glycoprotein receptor (GPIb-IX)
platelets can be activated in haemostasis by
platelet activating factor (PAF)
what forms initial haemostatic plug in small vessels and initial thrombus in arteries and veins
platelets
6 things that activate platelets
ADP, adrenaline, collagen, thrombin, PAF, high BP
In platelet activation, most chemicals bind and cause a change in shape from disc to
sphere
In platelet activation, change in shape to sphere causes
release of compounds involved in haemostasis from granules
Two receptors involved in platelet activation
GPIb-IX (von Willebrand Factor) and GPIIa-IIIb (fibrinogen)
In small vessels, blood coagulation factors interact to form secondary fibrin-rich…
haemostatic plug
In arteries and veins, blood coagulation factors interact to form secondary fibrin..
thrombus
fibrinogen is a precursor of
fibrin
Factor I is
fibrinogen
prothrombin is a precursor of
thrombin
Factor II is
Prothrombin
Factor III is (2)
Tissue factor (thromboplastin)
What does tissue factor activate?
Factor VII
Factor IV is
Calcium ion
Factor V is
Proaccelerin/ labile factor
2 actions of factor V
activates factor VII, combines with factor X to form prothrombin activator
Factor VII is also known as (2)
stable factor, serum prothrombin conversion accelerator
action of factor VII
activates factor X - EXTRINSIC PATHWAY
Factor VIII also known as
antihaemophilic factor
activity of factor VIII
activates factor X - INTRINSIC PATHWAY
Factor IX action
activates factor VIII
Factor X action
combines with factor V to form prothrombin activator
Factor XI action
activates factor IX
Factor XII action (3)
activates factorXI and plasmin, converts prekallikrein to kallikrein
Factor XIII also known as
fibrin-stabilising factor
Factor XIII action
cross linking of fibrin fillaments –> fibrin polymer = stabilises clot
role of platelet factor 1 (3)
activates factor VII, combines with factor X to form prothrombin activator, accelerates platelet activation
role of platelet factor 2
accelerates thrombin formation
role of platelet factor 3 (2)
aids in activation of factor VIII and prothrombin activator
role of platelet factor 4
bind heparin during clotting –> inhibit anticoagulant effect
3 pathways of blood clotting
extrinsic, intrinsic, common
3 lab tests for coagulation
thrombin time, prothrombin time, activated partial thromboplastin time (APTT)
Intrinsic pathway only uses clotting factors found in
blood
Which lab test is used to test intrinsic pathway
APTT (activated partial thromboplastin time)
Intrinsic pathway of coagulation
Platelets degranulate > release factor XII > Factor XI activated > Factor IX activated > calcium ion, PF3 and Factor IX activate Factor VIII > Factor X
Extrinsic pathway initiated by clotting factors from sources other than blood released by
damaged blood vessels and perivascular tissues
Extrinsic pathway of coagulation
tissue factor > combines with factor VII and calcium ion > activates factors IX and X > greatly accelerates coagulation
tissue factor is expressed in all cells other than
endothelial cells
clinical test for extrinsic pathway of coagulation
prothrombin time (PT)
damaged blood vessels and perivascular tissues release
tissue factor
final common pathway of coagulation is tested for by
Thrombin time (TT)
final common pathway of coagulation
Factor Xa (from extrinsic or intrinsic) combines with Factor III and V in presence of calcium ion and PF3 > prothrombin activator > acts of factor II > converts to thrombin > chops factor I (fibrinogen) to fibrin > combines with Factor XIII (fibrin stabilising factor) and calcium ion > fibrin polymer
fibrin polymer forms structural framework of
blood clot
in common pathway, thrombin works with factor V to accelerate production of
prothrombin activator
tissue repair is achieved by (2)
clot retraction and damage repair
process of clot retraction
after clot formation, platelets adhere to strands of fibrin > fibrin threads pulled > edges of broken vessel pulled together > clot compacts
process of damage repair
platelets and endothelial cells secrete platelet derived growth factor (PDGF) > stimulates fibroblasts and smooth muscle cells to multiply > repair damaged blood vessel > fibroblasts invade clot > produce fibrous connective tissue > helps strengthen and seal vessel whilst repair takes place
kallikrein action
converts plasminogen to plasmin (a fibrin dissolving enzyme)
factor XII catalyses formation of
kallikrein
thrombin activates
plasmin
most common hereditary clotting disorder
factor V leiden
deep vein thrombosis is part of group of problems together known as
venous thromboembolism
DVT affects how many /1000 people in UK every year
1/1000
3 symptoms of DVT
pain/tenderness of calf, swelling of calf, colour/temperature change of calf
risk factors /causes of DVT(12)
dehydration (sticky blood), male, obesity, pregnancy, over 60yrs old, contraceptive pill/ HRT, cancer, heart failure, conditions that cause thrombophilia, damage to inside lining of vein, immobility, spontaneous DVT
way of calculating likelihood of DVT (and PE)
Well’s score
NICE recommended Well’s scale is how many levels
2
Well’s scale for DVT from …. to ….
-2 to 9
score on Well’s scale meaning unlikely DVT
less that 2
score on Well’s scale meaning likely DVT
2 or more
Well’s scale for PE from … to …
0 to 12.5
Score on Well’s scale meaning unlikely PE
4 or less
Score on Well’s scale meaning likely PE
more than 4
D-Dimer test detects
pieces of blood clot that have been broken down and lost in bloodstream
D Dimer test isn’t always reliable as can increase after (4)
operation, injury, inflammation, pregnancy
additional tests to Well’s scale assessment needed to confirm DVT such as (2)
ultrasound, venogram
4 treatments for DVT
anticoagulation, compressive stockings, regular walking, raising leg when resting
2 causes of PE
DVT, embolus which is not clot
symptoms of PE (6)
breathlessness, coughing up blood, fever, tachycardia, chest pain, feeling faint
treatment for PE (6)
anticoagulants, oxygen, IV fluids, surgery, filters, thrombolysis
vitamin K has two types
vitamin K1, vitamin K2
vitamin K1 is found in
leafy green vegetables
vitamin K2
main storage form in animals
what is vitamin K required for? (4)
post-translational modification of certain proteins required for blood coagulation, metabolic pathways, bone, other tissues.
what in colon convert vitamin K1 > vitamin K2
bacteria
risk factors of blood clot formation (11)
obesity, pregnancy, immobility, smoking, over 60 yrs, diabetes, high BP, high cholesterol, trauma, oral contraceptives, inherited clotting disorders
