HEMA LEC - WEEK 3 (PRIMARY HEMOSTASIS)

hemostasis

Physiological process that involves the stoppage of bleeding

1. primary hemostasis

2. secondary hemostasis

2 phases of hemostasis

primary hemostasis

no coagulation

secondary hemostasis

involves platelets and coagulation system

primary hemostasis

Desquamation and small injuries to blood vessels

primary hemostasis

Involves vascular intima and platelets

primary hemostasis

Rapid, short-lived response

primary hemostasis

Rapid, short-lived response

secondary hemostasis

Large injuries to blood vessels and surrounding tissues

secondary hemostasis

Delayed, long-term response

secondary hemostasis

Tissue factor is exposed on cell membranes

1 - vasoconstriction

2 - platelet adhesion

3 - platelet aggregation

4 - fibrin-platelet plug formation

5 - fibrin stabilization

5 BASIC SEQUENCE OF EVENTS IN PRIMARY AND SECONDARY HEMOSTASIS AFTER VESSEL INJURY

Step 1: Vasoconstriction

Controlled by vessel smooth muscle; enhanced by chemicals secreted by platelets.

Step 2: Platelet adhesion

Adhesion to exposed subendothelial connective tissue

Step 3: Platelet Aggregation

Interaction and adhesion of platelets to one another to form initial plug at injury site

Step 4: Fibrin-Platelet Plug Formation

Coagulation factors interact on platelet surface to produce fibrin; fibrin-platelet plug then forms at site of vessel injury

Step 5: Fibrin Stabilization

Fibrin clot must be stabilized by coagulation factor XIII (fibrin stabilizing factor)

Fibrinolysis

___________ occurs after the primary and secondary hemostasis

Formation of platelet plug

End product of primary hemostasis

1. vascular response

2. platelet response

2 responses

1. prostacylin

2. adenosine

3. thrombomodulin

4. heparan sulfate

5. tPA

6. Von Willebrand Factor

7. 13-HODE

7 substances released:

collagen type I and II

Promotes platelet adhesion, aggregation and release reaction

1. prostacylin

2. heparan sulfate

3. tissue factor pathway inhibitor

4. nitric oxide

5. thrombomodulin

5 normal ECM suppresses hemostasis

primary hemostasis

refers to the role of blood vessels and platelets in the primary formation of platelet plug in response to vascular injury

Endothelin will binds to receptors in order to generate contraction

Once vessel injury occur, vessel spasm also occur in response to leaking of blood, the 1st mechanism is:

Myogenic action occurs if there is a direct contact to smooth muscle/vessel wall which will also lead to contraction that again will result to vasoconstriction

Once vessel injury occur, vessel spasm also occur in response to leaking of blood, the 2nd mechanism is:

Inflammatory receptors (Nociceptors) will be activated by prostaglandin and then initiate contraction which will lead to vasoconstriction

Once vessel injury occur, vessel spasm also occur in response to leaking of blood, the 3rd mechanism is:

Glanzmann's Thrombasthenia (GT)

lack of GP IIb/IIIa

Bernard-Soulier syndrome

lack of GP Ib; associated with platelet adhesion

1. nitric oxide

2. prostacylin (PGi2)

endothelium will secrete: (2) and bind to platelet, inactivate, to not adhere to endothelial cells

prostacyclin

-inhibits platelets activation and aggregation

nitric oxide

-inhibit platelet adhesion and aggregation

heparan sulfate (HS)

-secreted also by endothelial cells

-a natural anticoagulant

-inactivate thrombin

-thrombin will inactivate Factor II, IX, X

Thrombomodulin

-bind to activated protein C

-activated protein C will be inactivate

factor V

factor VIII

or labile factors

protein C will degrade to factor ____ and ____

factor II, IX, X

Thrombin will inactivate Factor ___, __, __

vascular intima

innermost vascular lining

factor X

factor VII will activate:

both intrinsic and extrinsic pathways

who will activate the common pathway?

von Willebrand factor (vWF)

synthesized by endothelial cells

thrombin

factor XIII is activated by:

to form a platelet plug

role of primary hemostasis

vasoconstriction

vascular response is:

prostacyclin

-inhibits platelet aggregation

-induces vasodilation

true

thrombin is a protein (true/false)

prothrombin

thrombin is from:

factor X

who activated prothrombin?

protein C

are vitamin K dependent (AKA regulatory protein)

thrombomodulin

Enhances anticoagulant activity of protein C

Protein C and Protein S

Vitamin K dependent

Factor V, VIII

Protein C will activate ___, ___

heparan sulfate

-Enhances activity of anti-thrombin III (ATIII)

antithrombin

inactivates thrombin

tPA

-converts plasminogen to plasmin

-in fibrinolysis

von Willebrand factor

responsible for platelet adhesion

13-HODE

inhibits platelet adhesion

1. collagen

2. fibronectin

3. basement membrane

3 exposure of platelets:

Type I

most common type of collagen

collagen

promote platelet adhesion, aggregation, and release mechanism

to form a fibrin clot

what is the function of RBC in blood vessel injury?

-fibrinogen

-platelet

-GP IIb/IIIa

involved in platelet aggregation (3)

Open canalicular system (OCS)

Platelet granules (all contents of platelets) move to the center of the platelet and fuse to the ______________

responsible for platelets aggregation

function of Thromboxane A2

dense granules, for aggregation

function of ADP

protrusion

Once all the contents are released, ____________ become visible which means they are already activated

1. collagen

2. thrombin

3. epinephrine

4. thromboxane A2

platelet release reaction are stimulated by (4)

1. Gp IIb/IIIa

2. with calcium

3, and fibrinogen

mediates ADP induced aggregation (3):

Glanzmann thrombasthenia

A condition associated with platelet aggregation

Bernard-Soulier syndrome

A condition associated with platelet adhesion

1. Gp Ib/VI

2. Gp Ib-IX-V

3. Gp IIb/IIIa

4. P2Y12

5. TPa

5 platelet receptos

1. Direct

2. Indirect

2 types of platelet adhesion

Direct adhesion

When there's injury, the collagen explode

Indirect adhesion

The VWF will stick to the collagen when there's injury and help the platelet to bind to it

1. Initial aggregation

2. Secondary aggregation

2 types of aggregation

Initial aggregation

-Caused by the release of granules and ADP from the adhering platelet

-Release of platelet to attact more

Secondary aggregation

Platelets form a link or bridge Gp IIb/IIIa

Glanzmann's Thrombasthenia

Deficiency in platelet aggregation results to:

Vasoconstrictor

Counterpart of prostacylin

Thromboxane

Stimulates platelet aggregation

Direct adhesion is the direct binding of platelets to exposed collagen at the site of injury, facilitated by platelet surface receptors.

Indirect adhesion involves the bridging of platelets to collagen by plasma proteins, such as von Willebrand factor (vWF), which binds to both collagen and platelet receptors, enhancing platelet adhesion.

Explain the direct and indirect adhesion

Initial aggregation involves platelets adhering to damaged blood vessels and releasing granules containing ADP, attracting more platelets and initiating activation.

Secondary aggregation occurs when activated platelets bind fibrinogen via GPIIb/IIIa receptors, forming a stable platelet plug.

Explain the initial and secondary aggregation

1. Collagen

2. ADP

3. Epinephrine

4. Thrombin

4 platelet stimulating agent

1. EC will release endothelin

2. Myogenic Effect

3. Pain receptor activaiton

3 reasons for vasoconstriction

Endothelin

Secrete chemicals going to receptor

Myogenic effect

Reaction with smooth muscle for contraction

Inflammatory chemicals

React to smooth muscle -> for contraction

1. EC secrete prostacyclin and release nitric oxide

2. Heparan sulfate

3. Thrombomodulin

3 reasons why blood is in liquid or fluid state

1. Prostacyclin

2. Nitric oxide

These 2 will inhibit or inactivate platelet, so wala na chance mag adhere and aggregate

Heparan sulfate

Binds to antithrombin III

Thrombomodulin

Binds to thrombin

Protein C

Protein that is attached to thrombin