coagulation and haemostasis Flashcards
(52 cards)
what is primary haemostasis?
Primary hemostasis occurs when platelets attach to a damaged or disrupted area of the endothelium. This adhesion allows the platelets to undergo a shape change and then aggregate together. Once adhered to each other a temporary platelet plug ‘primary haemostatic plug’ is created.
what is secondary haemostasis?
Secondary hemostasis is defined as the formation of insoluble, cross-linked fibrin by activated coagulation factors, specifically thrombin.
Fibrin stabilizes the primary platelet plug, particularly in larger blood vessels where the platelet plug is insufficient alone to stop hemorrhage.
which 3 mechanisms are involved in the formation of a stable haemostatiic plug?
Blood vessel constriction
Formation of platelet plug : platelet activation
Coagulation cascade: fibrin formation
what mechanisms does blood vessel injury trigger?
Blood vessel constriction (via neural action) Formation of platelet plug Coagulation cascade (via tissue factor)
what is the role of the endothelium?
- Synthesis of PGI2, vWF, plasminogen activators (TPA), thrombomodulin
- maintain barrier between blood and procoagulant subendothelial structures
what is the origin of platelets? properties?
from megakaryocytes
In the blood circulation, eeach megakaryocyte
produces ~4000 platelets.
Lifespan ~10 days, 1/3 stored in spleen
what is the structure of platelets - noteworthy stuff?
Surface glycoproteins:
GpIa, GpIb, GpIIb/IIIa
Dense granules:
ADP, ATP, Serotonin, Ca2+
a granules:
growth factors, fibrinogen, factor V, vWF
what is the mechanism of Platelet adhesion and aggregation? what factors are involved?
Platelet adhesion:
Tissue injury = platelets adhere to exposed subendothelial tissue via 2 WAYS:
- Via Gp1a (to collagen)
- Via Gp1b to vWF bound to collagen: more COMMON
Leads to Release of ADP & thromboxane
Platelet aggregation:
Platelets bind to fibrinogen (+ Ca2+) with the fibrinogen receptor aka Gp2b/3a.
This leads to activation cascade = more platelets join in
what are the biproducts in the metabolism of Arachidonic acid? what are their roles?
Arachidonic Acid is broken down by Cyclooxygenase enzymes and others forming:
Thromboxane A2 - Induces platelet aggregation
Prostacylin PGI2 - Inhibits platelet aggregation
what is the MOA of aspirin/ASA (Acetylsalicylic Acid) ?
MOA of NSAIDs?
Irreversibly blocks/inhibits the Cyclooxygenase 1 enzyme
preventing the formation of prostaglandin H2, and therefore thromboxane A2
NSAIDs - reversible effect
what does the term ‘tenase’ refer to?
the factors needed to activate factor 10.
they are slightly different in the ex/intrinsic pathways.
Intrinsic: Ca2+, FIXa, FVIIIa
Extrinisic: TF, Ca2+, FVIIa
what is the role of thrombin?
Cleaves Fibrinogen
Activates Platelets
Activates procofactors (FV and FVIII)
Activates zymogens (FVII, FXI and FXIII)
what is required to activate factor 2/prothrombin?
the prothrombinase complex:
Ca2+, FXa, FVa
what is the most important step in the coagulation cascade?
production of thrombin
as it catalyses the last step
what is the rate limiting step in fibrinogen formation?
production of FXa
what are the phases in the coagulatin cascade?
Initiation phase - small amounts of FXa production -> it binds to FVa
Amplification phase - The FXa/FVa complex converts small amounts of prothrombin into thrombin. Thrombin generated activates F8,5,11 and platelets locally. Leads to platelet activation
Propagation phase -
F10a/5a converts prothrombin into thrombin creating a “thrombin burst”.
The “thrombin burst”leads to the formationof a stable fibrin clot.
what is the redvance of Prothrombinase
Components binding and the Relative Rate
of Prothrombin Activation?
each component thatbinds leads to 10 fold increase in activation
when they all bind to lipid bilayer, there is 1000 fold increase.
what are the vit K dependent coagulation factors? made where?
F2,7,9,10
produced in the liver
how can a biliary tract issue lead to a coagulation defect?
vitamin k is fat soluble vitamin
needs bile
if bile duct obstruction -> can become vitamin k deficient
liver keeps on making the coagulation factors BUT they cant be activated (gamma carboxylation) due to lack of vit K
what are the different ways the body deals with blood clots?
- Fibrinolysis
- Antithrombins - heparin potentiates its effect
- Protein C/S - deactivate FVa, F8a - so those activating complexes dont form
- TFPI - tissue factor pathway inhibitor
describe the events in fibrinolysis?
the process is activated as soon a a clot forms
plasminogen is converted to Plasmin
Plasmin leads breakdown of Fibrin
activating enzymes of plasmin production = tPA, Urokinase
other stimulatory factors: Kallikrein, F11a, F12a
list some factors that inhibit fibrinolysis?
inhibit plasmin:
a2 plasmin
a2 macroglobulin
inhibit fibrin degradation:
TAFI; thrombin activated fibrinolysis inhibitor
how do antithrombins work?
they bind to proteoglycans on endothelial cells surface
stop thrombin generation
what is the mechanism in FV Leiden?
this mutation confers resistance to activated protein C
meaning that activated protein C cannot degrade F5a/8a
high levels of F8 also has the same effect
