Haemostasis and Thrombosis Flashcards
Haemostasis is the prevention of ???from damaged blood vessels
blood loss
Damage from a wound causes ???, adhesion and activation of platelets and formation of fibrin.
vasoconstriction
what forms a thrombosis?
Platelet activation and fibrin formation forms
three factors that predispose to thrombosis (Virchow triad): injury to the vessel wall, altered blood flow, and ???
abnormal coagulability
Blood coagulation involves the conversion of fibrinogen to fibrin by ??? (which can also cause platelet activation)
thrombin
??? is released following tissue damage to initiate blood coagulation
tissue factor
??? is a natural inhibitor of blood coagulation to prevent continual activation of this pathway
Antithrombin III
??? is an inherited disorder of increased coagulability
Thrombophilia
??? is an inherited disorder of decreased coagulability
Haemophilia
??? is a disease comprised mainly of platelets and fibrin, and usually associated with atherosclerosis
Arterial thrombosis
Venous thrombosis (or ‘blood clot’): comprised mainly of RBCs and ???. Can move through blood stream to form an embolus in the lung, heart, brain or other organ to cause ischaemia or infarction
fibrin
Membrane-bound ??? provides a non-thrombogenic surface on vascular endothelium, preventing platelet activation and coagulation
heparan sulfate
Vascular endothelium synthesizes
- Antithrombotic factors including ???
- Prothrombotic factors including ???
- prostaglandin I2, nitric oxide, adenosine, tissue plasminogen
activator and thrombomodulin (a thrombin receptor) - von Willebrand factor, tissue factor and plasminogen activator inhibitor (PAI-1)
Bacterial endotoxin and host cytokines alter antithrombotic and prothrombotic states of endothelium = promote disseminated intravascular coagulation in ???, ??? and other states
sepsis,
cancer
Drugs are used to treat or prevent thrombosis/ thromboembolism, targeting three distinct pathways:
1. Blood coagulation (fibrin formation)
2. Platelet function
3. ??? removal
Fibrin removal
Coagulation Cascade INTRINSIC or EXTRINSIC pathway: AKA the contact pathway. Activated by contact with artificial surfaces or exposed collagen, DNA, RNA or polyphosphates in damaged endothelium. No contribution to haemostasis in vivo
intrinsic
Coagulation Cascade INTRINSIC or EXTRINSIC pathway: AKA the in vivo or tissue factor (TF) pathway. TF abundant in adventitial cells surrounding blood vessels larger than capillaries, and in epithelial cells surrounding tissues
extrinsic
drugs that act on coagulation cascade (clotting effects): Factor VIII or IX is used to treat ???
haemophilia
drugs that act on coagulation cascade (clotting effects): recombinant factor VIIa is used to treat ???
severe bleeding
drugs that act on coagulation cascade (clotting effects): Vitamin K is used for excessive anticoagulation therapy (e.g. warfarin) and prevention of ??? disease in newborns
haemorrhagic disease
vitamin K promotes the carboxylation of ??? as it is a lipid soluble vitamin essential as a cofactor in the formation of this.
clotting factors
Drugs that Act on the Coagulation Cascade (Venous Thrombosis): heparin and low molecular weight heparins prevent/treat ??? but can cause haemorrhage, osteoporosis
thrombosis
Drugs that Act on the Coagulation Cascade (Venous Thrombosis): ??? is used to prevent/treat venous thrombosis as well as myocardial damage in angina and myocardial infarction. can cause haemorrhage and necrosis
warfarin
Drugs that Act on the Coagulation Cascade (Venous Thrombosis): Direct inhibitors of thrombin, prevent or treat venous throkmbosis but can cause minor haemorrhage and ???
gastrointestinal disturbances
heparin inhibits coagulation by activating ???
antithrombin III
Heparin and LMW heparin increase the inhibitory effect of ??? on factor IIa (thrombin) by binding both ??? and IIa = inhibit coagulation
antithrombin III
TRUE or FALSE: Heparin increases the inhibitory effect of AT III on Factor Xa by binding only AT III
TRUE
Warfarin inhibits ??? to reduce the reduced form of Active Vitamin K and the carboxylation of clotting factors
Vitamin K Reductase
Warfarin is metabolised by cytochrome P450 family 2 subfamily C member 9 (CYP2C9), which is polymorphic with varying activity between individuals. Use of warfarin requires monitoring to prevent
???
bleeding (haemorrhage)
Drugs that Alter Warfarin Activity: NSAIDS (aspirin); antibiotics (moxalactam, carbenicillin) all inhibit platelets and INCREASE or DECREASE warfarin action?
increase
Drugs that Alter Warfarin Activity: cephalosporins inhibit ??? reduction, increasing warfarin activity
vitamin k
Drugs that Alter Warfarin Activity: vitamin K causes coagulant activity opposing anticoagulant actIvIty of warfarin = INCREASE or DECREASE IN WARFARIN ACTIVITY?
DECREASE
TRUE or FALSE: anticoagulant drugs act on sites of factor XIIa, XIa, IXa, Xa, IIa, XIIIa
true
platelet activation:
1. ruptured plaque or tissue damage = adhesion of platelets to ??? surface = activation
thrombogenic
platelet activation:
2. ??? = activation of platelets
thrombin
platelet activation can lead to Arachadonic Acid generation = production of cyclic endoperoxidases = synthesis of TXA2 = expression of GP IIb/IIIa receptors = linkage of adjacent platelets by fibrinogen binding = ???
aggregation of platelets
aspirin impairs ??? activity by inhibiting cyclogenase-1 and thromboxane A2 synthesis to prevent thrombotic stroke and heart attack
platelet activity
dipyridamole inhibits ??? aggregation to reduce risk of stroke and death during ischaemic attacks
platelets
Clopidogrel, prasugrel and ticagrelor are drugs that impair platelet activity by inhibiting ??? receptors for acute coronary syndromes
P2Y12 receptors
aspirin reduces the action of ??? triggering production of cyclic endoperoxides to work as an antiplatelet drug
arachadonic acid
drugs that promote fibrinolysis (thrombolysis): streptokinase activates ??? to reduce myocardial infarction, thrombotic stroke, etc
plasminogen
