Blood Coagulation

Question 1

name the 4 steps in hemostasis

Answer 1

1. vascular spasm/vasoconstriction
2. platelet plug formation/ primary hemostasis
3. blood coagulation/ secondary hemostasis
4. dissolution of the fibrin clot/ tertiary hemostasis

Question 2

describe the contraction during vascular spasm

Answer 2

• local myogenic spasm
• factors releasd from the injured vessel wall are endothelin and serotonin which causes contraction

Question 3

name the stages of platelet plug formation (primary hemostasis)

Answer 3

• platelet adhesion to the damaged surface and activation
• platelet aggregation

Question 4

describe the steps of platelet adhesion

Answer 4

1. platelet GP1a binds to collagen
   
   1. structural changes e.g. development of pseudopods to promote platelet-platelet interaction
2. Von Willibrand factor (binds to collagen and GP1b) binds to platelet receptor GP1b resulting in changes in the platelet membrane
   
   • GpIb defect = Bernard Soulier syndrome
3. binding also exposes GPIIb/IIIa for binding of fibrinogen

Question 5

describe the role of vWF

Answer 5

• vWF acts as a bridge between GPIb on the surface of platelets and collagen fibers; facilitates platelet adhesion to the vessel wall and platelet aggregation
• vWF complexes with factor VIII; carries it, stabilizes it and prevents its degradation
• vWF deficiency:
  
  • defect in the formation of the platelet plug (primary hemostasis)
  • defect in coagulation (due to low levels of factor VIII)–defect in secondary hemostasis

Question 6

describe platelet activation and shape change

Answer 6

• release of platelet granule contents (ADP) that activate other platelets, promoting aggregation
• binding of ADP to its receptor facilitates the release of Ca2+ and decreases intracellular cAMP levels
  
  • aggregation of platelets cannot take place without ADP stimulation
• release of Ca2+ facilitates formation of thromboxane A2
  
  • ​TXA2 induces platelet aggregation by activating other platelets

Question 7

describe the platelet aggregation step

Answer 7

• platelet aggregation is mainly mediated by fibrinogen
• fibrinogen binds to GPIIb/IIIa on adjacent platelets
  
  • defect in GpIIb/IIIa = Glansmann Thrombasthenia = platelet aggregation defect

Question 8

describe the extrinsic pathway

Answer 8

severe tissue damage

• tissue injury –> release of tissue factor aka factor III
• Factor VII is activated by factor III into VIIa (a = activated)
• Factor VIIa and tissue factor (factor III), in the presence of Ca and platelet phospholipids, activate factor X into Factor Xa

Question 9

describe the intrinsic pathway

Answer 9

activated by minor endothelial damage

• Factor XII becomes activated to XIIa
• XIIa activates XI
• XI activates IX
• IXa complexes with VIIIa in the presence of Ca on the platelet plug
• this activates X

Question 10

describe the formation of thrombin in the common pathway

Answer 10

• Xa will complex with Va in the presence of Ca on the platelet plug
  
  • forms the prothrombinase complex
• Prothrombinase complex splits prothrombin to form activated thrombin

Question 11

explain the role of thrombin

Answer 11

• thrombin activates factor VIII (intrinsic) and factor V (common) and amplifies the clotting cascade
• thrombin also converts fibrinogen to fibrin and helps in the formation of the “soft clot”
  
  • thrombin then activates factor XIII which converts it into the “hard clot”

Question 12

explain the conversion of fibrinogen to fibrin

Answer 12

• Fibrinogen has fibrinopeptides that are cleaved by thrombin, which converts it into fibrin monomers
• the fibrin monomers aggregate to form the soft clot of fibrin (unstable clot linked by noncovalent bonds)

Question 13

how to convert soft clot to hard clot?

Answer 13

• thrombin (factor IIa) activates Factor XIII to catalyze stable covalent links between fibrin monomers to form the hard clot