Haemostasis ✅

Question 1

what is homeostasis?

Answer 1

the natural process of the body’s normal physiological response that prevents significant blood loss (bleeding or hemorrhage) after vascular injury.

an integral part of a complex and well-regulated system that keeps blood clot free and as a fluid in normal blood vessels, but forms a localized plugin injured vessels.

Question 2

homeostasis balance

Answer 2

Question 3

what are the major players in hemostasis?

Answer 3

depends on:
blood vessel wall;
platelets and other blood cells
coagulation proteins and other proteins.

hemostasis is a finely tuned process and a complex biochemical network

Question 4

what are the 4 steps of hemostasis

Answer 4

• localized vasoconstriction
• primary haemostasis
• secondary haemostasis
  -tertiary haemostasis

Question 5

what is localized vasoconstriction?

Answer 5

reduces blood flow to the injury site and retards blood loss.
vasoconstriction mediated by reflex neurogenic mechanisms and released vasoconstrictors.
transient - typically lasts 30 mins

Question 6

primary hemostasis

Answer 6

platelet plug formation
- plugs the breach in the blood vessel

the endothelium acts as a physical barrier that separates circulating platelets from thrombogenic substances in the extravascular space.

there are 4 main events:
-platelet adhesion
-platelet activation
-platelet aggregation
-platelet plug formation

Question 7

secondary haemostasis

Answer 7

blood clotting/coagulation
- strengthens and reinforces platelet plug

Question 8

tertiary hemostasis

Answer 8

fibrinolysis
- dissolves the clot once blood vessel has been restored

Question 9

platelet adhesion

Answer 9

endothelial injury - platelets bind to exposed subendothelial matrix proteins via transmembrane glycoproteins receptors.

Question 10

platelet activation

Answer 10

adherent platelets undergo this process:
shape change- to elongated cells with cytoplasmic extensions
granule release - release of contents of preformed cytoplasmic granules.
membrane phospholipid metabolism - increases thromboxane A₂ (TXQ₂) production
activation and expression of gpIIb/IIIa receptors.

Question 11

key steps in primary haemostasis
platelet aggregation and plug formation

Answer 11

agonist-activated platelet GPII/IIIa receptors bind to fibrinogen - cross bridges with adjacent platelets - formation of a primary haemostatic plug.

Question 12

what is the primary haemostatic plug sufficient to do?

Answer 12

sufficient to stop haemorrhage in small blood vessels but not in larger vessels where there is severe injury.

activated and aggregated platelets form the phospholipid membrane surface for the clotting process (secondary hemostasis)

Question 13

primary haemostasis diagram

Answer 13

Question 14

secondary hemostasis - coagulation cascade

Answer 14

• forms a stable fibrin clot at the site of injury

involves serial activation of coagulation
factors - formation of insoluble, cross-linked fibrin - stabilization of the primary platelet plug - solid, irreversible clot (secondary haemostatic plug)

Question 15

secondary hemostasis - coagulation cascade

Answer 15

• forms a stable fibrin clot at the site of injury

involves serial activation of coagulation
factors - formation of insoluble, cross-linked fibrin - stabilization of the primary platelet plug - solid, irreversible clot (secondary haemostatic plug)

Question 16

what are the three interacting pathways of the coagulation cascade?

Answer 16

intrinsic - slow, collagen.
extrinsic - fast, tissue factor
common pathway

Question 17

intrinsic pathway

Answer 17

slower responding.
blood comes into contact with collagen in damaged blood vessel walls.
FXII (Hageman factor) forms a primary complex with HMKW and prekallikrein on collagen - activation of FXII
FXIIa activates factor XI; FXIa then activates IX
FIXa forms a complex with FVIIIa (as a cofactor), ca++ & phosphatidylserine (intrinsic tenase), which activates FX (common pathway) - thrombin generation.

Question 18

extrinsic pathway

Answer 18

quick responding pathway which begins as soon as tissue damage is present, e.g. traumatic injury.
when in contact with blood, damaged extravascular cells release tissue factor. Tissue factor forms a complex with FVII and cA++, known as extrinsic tenase, an extrinsic pathway factor X activator. TF-FVIIa complex activates FX of the common pathway, thrombine FLLa generation. this complex can also activate the factor IX of the intrinsic pathway as an alternative.

Question 19

common pathway

Answer 19

both the intrinsic and extrinsic pathways converge together and activate.
they converge at factor Xa (10a) or to the production of fibrin, which seals of the breach in the blood vessel.

Question 20

components of the coagulation cascade

Answer 20

Question 21

tertiary haemostasis (fibrinolysis) for coagulation

Answer 21

dissolves and removes fibrin clots following secondary hemostasis.
ensures localization of fibrin clot formation and lpt removal for when the wound is healed.

Question 22

what are the 5 steps of the common pathway for coagulation?

Answer 22

activation of FX
conversion of prothrombin (FII) to thrombin (FIIa)
cleavage of fibrinogen (FI) to fibrin (FIa)
polymerization of fibrin
stabilization of fibrin polymers by FXII

Question 23

what are the limitation of the coagulation cascade?

Answer 23

doesn’t fully explain how blood clots in vivo
assumes both intrinsic and extrinsic pathways are independently capable of clot formation

Question 24

modern cell based model for secondary haemostasis

Answer 24

Question 25

tertiary hemostasis | fibrinolysis

Answer 25

dissolves and removes fibrin clots following secondary hemostasis
ensures localization of fibrin clot and clot removal after wound healing
mediated by plasmin, a proteolytic enzyme that degrades fibrin mesh

process involves:
release of plasminogen activators
plasmin production from the inactive precursor, plasminogen
clot lysis and release of degradation products.

Question 26

regulation of hameostasis

Answer 26

primary and secondary hemostasis must be restricted to the local site of the injury

size of the primary and secondary hemostatic plug must be restricted - to keep blood vessel patent

the fibrinolytic system must be regulated - to ensure the removal of unwanted fibrin clots and the preservation of fibrin in wounds.

regulation is achieved via a combination of multiple endogenous antithrombotic and antifibrinolytic systems.