PATH - 9-21 - Normal Hemostasis

Question 1

A: What 3 Major entities does Hemostasis depend on?

B: What’s the FIRST step to Primary Hemostasis during vessel damage? What 3 things mediates this?

Answer 1

1. Blood Vessel Wall (Endothelium and SubEndothelium)
2. Platelets and [Platelet release products]
3. Coagulation and Fibrinolytic systems

B: [Transient VASOCONSTRICTION] is the first thing to occur when endothelium is damaged! This occurs due to:

• [Reflex Neurogenic stimulation]
• EndoThelin from Endothelial cells
• [ECM Contractile fibers]

Question 2

A: 4 Steps of Platelet ADHESION

B: Describe the Platelet

[Light alpha granules] (7)

C: Why is Platelet ADHESION so important?

Answer 2

Steps of Platelet Adhesion

1st: Vessel injury exposes [SubEndothelial collagen and fibronectin]
2nd: [Von Willebrand factor] binds to this [SubEndothelial collagen]
3rd: Platelets bind to vWF with their [GP1b receptor] and this activates them –> shape changes from discoid to non-discoid—> Degranulate to release [Platelet factors]
4th: [Platelet factors] RECRUIT more platelets to injury site

B: Describe the Platelet [Light alpha granules] vs. [Dense Beta Granules]:

LAG= PF4 /PDGF / vWF / fibrinogen / fibronectin / [Factors 5 and 8] / TGFb

C: Platelet ADHESION prevents blood flow from dislodging and unplugging

Question 3

Where does Von Willebrand factor come from? (2)

Answer 3

1. Endothelial [Weibel-Palade bodies]
2. [Platelet (Light alpha granules)]

Question 4

Secondary hemostasis:
A: At the same time of vWF secretion, _______ is released at the injury site from _______ and combines with _______ to initiate the plasma coagulation cascade—> ultimately forming _______.

B: coagulation proteins form complexes on the _______utilizing phospholipids from the _______ membrane.

C: Describe Fibrin polymerization

1. How is Fibrin related to aggregated platelets?

Answer 4

Secondary hemostasis:
A: At the same time of vWF secretion, [tissue factor thromboplastin] is also released at the injury site from endothelial cells. [Tissue Factor Thromboplastin] combines with [PF 7] to initiate the plasma coagulation cascade—> ultimately forming [Thrombin Factor 2A].

B: coagulation proteins form complexes on the platelet surface utilizing phospholipids from the platelet membrane.

C: Fibrin polymerization occurs when [Transamidase Factor 13A] polymerizes /stabilizes/crosslinks [Fibrin 1A] —> Fully Stable

1. Stabilizes and anchors aggregated platelets

Question 5

During Platelet Aggregation:

1. Platelets aggregate at injury site using their ______ Receptors] and ______ as linking molecules. This is AFTER ______ has occurred.
2. Platelet Aggregation Ultimately forms a______

3. What stage of Hemostasis is this?

Answer 5

During Platelet Aggregation:

1. Platelets aggregate at injury site using their [GP2b3A Receptors] and Fibrinogen as linking molecules. This is AFTER Adhesion has occurred.
2. Platelet Aggregation Ultimately forms a [Weak Platelet Plug]

3. Primary Hemostasis

Question 6

A: How does a [PERMANENT Platelet Thrombin Plug] form? (3)

B: Which 2 other cell types become apart of this PPtP?

Answer 6

1. [Thrombin Factor 2A] stimulates recruitment and activation of additional platelets.
2. [Thrombin Factor 2A] enzymatically converts fibrinogen to fibrin. Fibrin serves to bind (stabilize) and anchor the aggregated platelets.
3. The consolidated platelet-fibrin clot (thrombin) forms a [PERMANENT Platelet Thrombin Plug] which seals the hole in the vessel wall.

B: Erythrocytes and leukocytes become part of the thrombus. –> could lead to INC in thrombus size

Question 7

A: True or False

Endothelial cells also have a ANTIThrombotic effect (its normal state)

B: How does Endotheliium prevent thrombosis? (3)

Answer 7

A: TRUE

B:

Intact endothelium prevents platelets and coagulation

proteins from coming into contact with subendothelial collagen.

2. secrete prostacyclin and nitric oxide that prevent platelet aggregation.

Question 8

A: How does Endothelium prevent Coagulation? (3)

B: How does Endothelium particpate in Fibrinolysis?

C: When does Endothelium become PROthrombotic?

Answer 8

A:

1. Endothelium secretes [Protein S] which is a required cofactor for [Protein C].
2. Endothelium contains [Heparin-like molecules] that combine with [Antithrombin 3] to, together, DEACTIVATE [Thrombin PF2A]
3. Endothelium contains ThromboModulin which modulates Thrombin to instead activate [Protein C]–(with Protein S)—> DeActivates [PF8A and 5A]

B: Endothelium secretes [tissue Plasminogen Activator] which (after Plasminogen is converted into Plasmin) will lyse fibrin and fibrinogen

C: When intact Endothelium becomes COMPROMISED during injury and anticoag mechanisms are lost

Question 9

A: DeActivated Platelets are _____ and _____

B: Which Platelet Factor neutralizes Heparin?

C: List the 5 Platelet Glycoprotein receptors on its surface

Answer 9

A: DeActivated Platelets are Discoid and anuclear

B: Platelet Factor 4

C:

1) [GP-2b-3A] –>allows Platelet Aggregation
2) [GP1b] —> allows Platelet ADHESION
3) Thrombin
4) Serotonin
5) ADP

Question 10

Describe the Platelet:

[Dense Beta granules] (7)

Answer 10

Describe the Platelet [Dense Beta Granules]:

[Dense Beta Granules] = CHASE = Ca+ / Histamine / [ADP-ATP] / Serotonin / EPi

Question 11

How is the intrinsic coagulation pathway activated? (2)

Answer 11

1st: Phospholipid complex is activated when negatively charged phospholipids become exposed on the platelet surface after [Platelet Adhesion] .
2nd: This complex serves as a site on which coagulation factors combine with ionized calcium (released from dense granules) to activate the intrinsic

pathway of the coagulation cascade to form thrombin

Question 12

What Coagulation Factors are apart of the Fibrinogen Group? (4)

Answer 12

Fibrinogen Group

Factors 1 / 5 / 8 / 13

Question 13

A: What Coagulation Factors are apart of the ProThrombin​ Group? (4)

B: What 3 things do this group all share in common?

Answer 13

Prothrombin Group:

Factors 2 / 7 / 9 / 10

B: 􏰀

1. All contain [carboxy glutamic acid] (needed for the binding

to calcium).

2. All are synthesized in the liver
3. All are vitamin K dependent.

Question 14

A: What Coagulation Factors are apart of the Contact​ Group? (4)

B: Which of these participate in the actual activation of the intrinsic pathway (2)

Answer 14

Contact Group:

Factors 11 / [12 -Hageman] / [PrekaLLikrein FLetcher] / [HMWK Fitzgerald]

B: [Prekallikrein Fletcher] and [HMWK Fitzgerald]

Question 15

How does Lupus play a role in INHIBITING Thrombosis?

Answer 15

Lupus antibodies can be anti-coagulant and [anti-phospholipid]

Question 16

A. Describe [Antithrombin 3] (2)

B: Congenital deficiencies of [Antithrombin 3] result in _______.

C: [Heparin cofactor 2]

D: [Tissue factor pathway inhibitor] (2)

Answer 16

A. [Antithrombin 3] is a [plasma inhibitor] which ALSO binds to [Heparin/Heparin-like moelcules] —> inhibits [Factors (Thrombin 2A) / 10A / 9A] .

B: Congenital deficiencies of this inhibitor result in thrombophilia.

C: [Heparin cofactor 2] is a weak inhibitor of thrombin.

D: [Tissue factor pathway inhibitor] is a STRONG inhibitor of tissue factor and is responsible for some of the anticoagulant effects of heparin.

Question 17

A: 3 Criteria of Virchow’s Triad for INC Thrombosis

B: Describe the order of causation

Answer 17

1. Endothelial Cell Injury
2. Abnormal Blood Flow / Stasis
3. Hypercoagulability

B: H <——E ⇔ A —–> H

Question 18

A: 4 Risk Factors for INC Hypercoagulability

B: What are the differences between Primary and Seconary Hypercoagulability?

C: List the specific risk factors (High vs. low) for [Secondary Hypercoagulability] (6)

Answer 18

• Age
• Smoking
• Oral Contraception
• Diet (Hyperlipidemia)

B: Primary vs. Secondary

Primary = Genetic

Secondary = ACQUIRED

1. High risk: Sepsis/CA/Trauma
2. Low risk: Pregnancy/hyperlipidemia / drugs