Hemostasis

Question 1

Define hemostasis

Answer 1

Steps taken by the body to limit blood loss

Question 2

What are the four steps of hemostasis

Answer 2

1) Vascular spasm 2) Formation of platelet plug 3) Formation of blood clot 4) Damage repair

Question 3

Where is TPO synthesized? What triggers its release?

Answer 3

Liver It is constantly being released into the blood

Question 4

How are TPO levels controlled in the blood?

Answer 4

Internalization and destruction by circulating platelets

Question 5

What is the receptor for TPO?

Answer 5

MPL

Question 6

What is the overall effect of thrombopoeisis?

Answer 6

Increased division and maturation of ALL BLOOD CELL LINEAGES

Question 7

What pathway does TPO act on?

Answer 7

JAK2/STAT25

Question 8

• What are some of the components of platelets?

Answer 8

• Actin and myosin
• Mitochondria
• Remnants of ER (for Ca2+ storage)
• COX 1 (formation of thromboxane, arachidonic acid and prostaglandins)
• Fibrin stabilizing factor (clot stability)
• Platelet derived growth factor (repair)
• Serotonin 5HT-

Question 9

• The cell membranes of platelets have what 3 features?
• What is the function of each?

Answer 9

• Glycoproteins (when activated), phospholipids, collagen receptors
• Glycoproteins help make membrane sticky
• Phospholipids contain platelet factor 3 and help activate clotting cascade
• Receptors for collagen enable platelet binding

Question 10

• What type of response is a vascular spasm?
• What is the function of a vascular spasm?

Answer 10

• myogenic response (meaning that the smooth muscle surrounding the vasculature will contract on its own)
• Goal is to stop blood flow out of the hemorrhaged area

Question 11

• What else occurs during step 1 (vascular spasm)?

Answer 11

• Release of vasoconstricting agents from platelets (serotonin and thromboxane a2)

Question 12

• How is the platelet plug formed?

Answer 12

• Collagen is exposed on damaged membrane and enables platelets to bind
• For platelet to bind, 2 steps occur (1) Von Willebrand Facrtor and (2) binding of platelet receptor (integrin) to collagen
• Activation of platelet
• Platelet swelling and contraction
• Release of granules from the platelets
• More platelets are recruited and stick to one another via thromboxane A2 and ADP

Question 13

• What are the three key steps in coagulation?

Answer 13

• Activation of thrombin regulator
• Activation of thrombin
• Creation of fibrin from fibrinogen

Question 14

• What is the role of platelet derived growth factor in tissue healing

Answer 14

• Stimulates fibroblasts to grow into clotted area
• These fibroblasts differentiate into smooth muscle to close the hole

Question 15

• What enzymes and proteins are important in the removal of clots?

Answer 15

• tPA
• tPA inhibitor
• Plasminogen
• Protein C

Question 16

• What is the function of plasminogen when it is activated into plasmin?
• Where is plasminogen synthesized/stored?

Answer 16

• Lyses fibrin to destroy clot
• Synthesized in liver
• “Stored” in plasma

Question 17

• How is plasminogen converted into its active form?

Answer 17

• tPA inhibitor is inhibited by protein C
• tPA can activate plasminogen

NOTE: tPA is released in response to damaged tissye and is normally inhibited by tPA inhibitor (why we need protein c)

Question 18

• What are some of the ezymes/molecules that prevent clots from forming in the first place?

Answer 18

• FIbrin
• Prostacyclin
• Antithrombin
• Protein C

Question 19

• What are some physiological factors that inhibit clot formation?

Answer 19

• Smooth endothelial lining of vessels (interrrupted in diseases like atherosclerosis)
• Continuous flow of non-turbulent blood
• Platelet repelling action of glycolax
• Endogenous anticoagulants
• PKC

Question 20

• What are some examples of endogenous anticoagulants?

Answer 20

• Heparin
• Prostacyclin
• Anti-Thrombin II

Question 21

• In addition to inhibiting tPA inhibitor, what else does PKC do?

Answer 21

• Inactivates Factors 5 and 8
• This inactivation PROMOTES DESTRUCTION OF FIBRIN