L2: Physiological basis of haemostatic mechanisms

Question 1

What is the definition of hemostasis?

Answer 1

Prevention of blood loss after injury.

Question 2

What are the steps of hemostasis?

Answer 2

• Vascular spasm: occurs immediately after the blood vessel has been cut
• Formation of a platelet plug (temporary hemostatic plug).
• Formation of a blood clot (definitive hemostatic plug).
• Fibrosis of the blood clot to close the hole in the vessel permanently.

Question 3

What does vascular constriction result from?

Answer 3

• Nervous reflexes are initiated by the pain from the traumatized vessel.
• Local myogenic contraction due to direct damage.
• Local vasoconstrictor factors as serotonin and thromboxane A2 (from platelets).

Question 4

What causes more constriction to the vascular walls?

Answer 4

Transverse cut & traumatized vessels “nervous reflex”

Question 5

What is the function of vascular spasms in blood clotting?

Answer 5

The vascular spasm reduces the flow of blood from the vessel rupture.

Question 6

What is the functional structure of the platelet membrane?

Answer 6

☺ It is extensively invaginated membrane with a complex canalicular system that allow contact with the ECF.

☺ Contain a coat of glycoprotein
• Repulses adherence to normal endothelium
• Allow adherence to the injured vessel wall.

☺ Contains large amounts of phospholipids
• Play several roles in the process of blood clotting.

Question 7

What is the Functional structure of the platelets cytoplasm?

Answer 7

Contains many active structures as:
- Contractile proteins for platelet contraction as actin, myosin, and thrombosthenin

• Residual of both endoplasmic reticulum and Golgi apparatus for synthesis of enzymes and storage of Ca2+.
• Mitochondria
  • Can form ATP & ADP.
• Enzyme system
  • Can synthesize prostaglandins
• Clotting factors as fibrin-stabilizing & von Willebrand factors
• A growth factor that helps repair damaged vessel walls.

Question 8

What are the steps of the formation of the platelet plug?

Answer 8

Platelet adhesion
Platelet activation
Platelet aggregation

Question 9

What is the adhesion of platelets potentiated by?

Answer 9

Such adhesion is potentiated by the von Willebrand factor (a glycoprotein presents in the plasma and subendothelial tissue) and the platelets membrane glycoprotein

Question 10

When do platelets adhesion take place?

Answer 10

When a blood vessel is injured, the platelets adhere to the exposed subendothelial collagen.

Question 11

What initiates platelet activation?

Answer 11

Initiated by platelet adhesion.

Question 12

What happens in platelet activation?

Answer 12

• The activated platelets swell, develop pseudopodia, become sticky, and discharge their granules mainly ADP.
• Also, its enzyme system is activated to form thromboxane A2. “VC”

Question 13

What happens in platelet aggregation?

Answer 13

• The released ADP and thromboxane –A2 activate the nearby platelets, Making them stickier and adhere to the originally activated platelets and release ADP and thromboxane – A2 which, in turn, activates more and more platelets.
• Thus, a vicious circle of platelets activation and aggregation is elicited leading to the formation of a loose platelet plug. “Purpura is due to non-formation or non-function of platelets”

Question 14

What is the effect of salicylates (aspirin) on blood clotting?

Answer 14

Salicylates (aspirin) can inhibit the thromboxane –A2 formation and so inhibits platelets activation and aggregation.

Question 15

What is the importance of platelet plugs?

Answer 15

Platelet plugs are extremely important for closing the minute ruptures occurring in the wall of vessels many thousand times daily

Question 16

What is the duration of blood clot formation?

Answer 16

The active process occurs within 3-6 minutes.

Question 17

What does blood clot formation need?

Answer 17

• The clotting process is initiated by active substances from the traumatized vascular wall, platelets, and coagulation factors.
• The clotting process to occur, certain factors named clotting factors (plasma protein of beta globulin type) must be activated.

Question 18

What are the clotting factors?

Answer 18

• Plasma proteins of beta globulin type, are proteolytic enzymes present in an inactive form

Question 19

Give examples of the clotting factors.

Answer 19

Factor I: Fibrinogen

Factor II: Prothrombin

Factor III: Tissue thromboplastin

Factor IV: Calcium ions (Ca++)

Factor V: Proaccelerin or labile factor

• ——- Prekallikrein
• ——- HMW kininogen
• ——- Platelets F3

Factor VII: Proconvertin or stable factor

Factor VIII: Antihaemophilic factor

Factor IX: Christmas factor

Factor X: Stuart prewar factor

Factor XI: Plasma thromboplastin antecedent

Factor XII: Hegeman factor

Factor XIII: Fibrin stabilizing factor

Question 20

What are the steps of clot formation?

Answer 20

 Formation of prothrombin activator
 Conversion of prothrombin into thrombin
 Conversion of fibrinogen into fibrin

Question 21

What initiates the extrinsic pathway?

Answer 21

It is initiated by contact of blood with traumatized vascular walls or extra-vascular tissues.

Question 22

Mentions steps of the extrinsic pathway.

Answer 22

It is a rapid process and occurs according to the following steps:
- Traumatized tissues release a complex of several factors called tissue thromboplastin (composed of phospholipids and lipoprotein that functions as a proteolytic enzyme).

• The lipoprotein of tissue thromboplastin activates factor VII and then complexes with it.
  • This complex in the presence of Ca2+ and tissue
  phospholipids act on factor X to form activated factor X
• Formation of the prothrombin activator.
  • The activated factor X complexes immediately with the
  tissue phospholipids, Ca2+and with activated factor V to form the complex called prothrombin activator.

Question 23

What initiates the intrinsic pathway?

Answer 23

It begins with trauma to the blood itself or exposure of the blood to collagen from a traumatized vessel wall or contact of the blood with water – wettable surface e.g., glass.

Question 24

What are the steps of the intrinsic pathway?

Answer 24

It continues through the following series of cascading reactions:
1) Trauma to the blood or exposure of the blood to vascular wall collagen “slow blood flow, roughy intima”

2) leads to 2 effects; first, activation of factor XII; second, the release of platelet phospholipids (platelet factor 3 or PF3).

3) The activated factor XII activates factor XI.
• This reaction requires high molecular weight kininogen
(HMW) and is accelerated by prekallikrein

4) The activated XI acts on factor IX to activate it.
5) The activated factor IX together with factor VIIIa and platelet phospholipids (PF3) activate factor X.
6) The activated factor X combines with activated factor V, Ca2+, and platelets phospholipids to form the prothrombin activator

Question 25

Compare between the extrinsic and intrinsic pathway of blood clotting in terms of duration and site

Answer 25

In vivo, 15-20 sec

In vivo and vitro, 3-6 min

Question 26

What are the steps of conversion of prothrombin into thrombin?

Answer 26

After the prothrombin activator has been formed, it causes the conversion of prothrombin to thrombin in the presence of sufficient amounts of Ca2+.

Question 27

What are the steps of conversion of fibrinogen into fibrin?

Answer 27

• Formed thrombin removes 4 low-molecular-weight peptides from each molecule of fibrinogen, forming a molecule of fibrin monomer.
• Many fibrin monomer molecules polymerize within seconds into long fibrin threads that constitute the meshwork of the clot.
• Within a few minutes after the clot is formed a substance called fibrin stabilizing factor, released from the platelets, strengthens the fibrin meshwork by adding more and more bonds between the fibrin monomer molecules and formation of multiple cross-linkages between the fibrin thread.
• Finally, the firm blood clot is formed which is composed of a meshwork of fibrin threads running in all directions and entrapping blood cells, platelets, and plasma.

Question 28

What is the fate of the clot?

Answer 28

• It can become invaded by fibroblasts, which subsequently form connective tissue till the clot is completely organized into fibrous tissue within about 1 to 2 weeks. “Permanent healing”
  • This course usually happened with the clot that is formed in a small hole in the vessel wall.
• It can dissolve:
  • This usually occurs with the clots formed in the tissues.

Question 29

What is the role of calcium in clotting mechanisms?

Answer 29

• Except for the first two steps in the intrinsic pathway, Ca2+ is required for acceleration of all the blood clotting reactions.
• Therefore, in the absence of Ca2+, blood clotting by either pathway does not occur.

Question 30

How is blood removed from a person prevented from clotting?

Answer 30

either by de-ionizing the calcium by addition of citrates or by precipitating the calcium by oxalates.

Question 31

What is the importance of vitamin K in blood clotting?

Answer 31

Vitamin K “from the colon” is necessary for the liver formation of five important clotting factors, prothrombin, factor VII, Factor IX, Factor X, and protein C. “1972”

Question 32

What happens in cases of absence of vitamin K?

Answer 32

In the absence of vitamin K, deficiency of these coagulation factors results in serious bleeding tendencies (so it is called antihemorrhagic vitamin).

Question 33

Why are platelets important for clot retraction?

Answer 33

• They become attached to the fibrin threads in a way that they bind different threads together.
• Platelets secrete fibrin stabilizing factor (factor XII) which causes more cross-linking bonds between the fibrin threads.
• Activation of the platelet contractile proteins by thrombin and Ca2+ cause strong contraction of the platelet attached to the fibrin.

Question 34

What is the importance of clot retraction?

Answer 34

the edges of the broken blood vessels are pulled together, thus contributing to the ultimate state of hemostasis.

Question 35

What happens after a clot is formed?

Answer 35

After a clot is formed, it begins to contract & a clear yellowish fluid is squeezed called serum

Question 36

What are the functions of platelets in hemostasis?

Answer 36

1) Induces vascular spasm (serotonin & thromboxane A2)
2) Formation of primary platelet plug
3) Release of platelets phospholipid (Pf 3) which is essential for clotting mechanism.
4) Stabilization of blood clot (fibrin – stabilizing factor)
5) Clot retraction (Ca2+).
6) Repair of damaged vessels wall (platelet-derived -growth factor)