Hemostasis

Question 1

Platelet Production in Hematopoiesis

Answer 1

Megakaryocytes arise from the precursor cells

In the process of hematopoiesis there is the production of platelets, which are derived from megakaryocytes

Question 2

What increases platelet numbers?

Answer 2

Thrombopoietin increases platelet numbers

Question 3

Three phases of hemostasis

Answer 3

Vascular phase
- There is damage to the blood vessel
- Vasoconstriction of a vessel

Platelet phase
- Platelets adhere and release platelet factors that are going to form a loose platelet plug

Coagulation phase
- The tissue underlying the blood vessel will trigger the coagulation cascade, the formation of thrombin, which converts fibrinogen to fibrin (strands that reinforce the platelet plug

Question 4

Describe the unique production of platelets from Megakaryocytes.

Answer 4

Megakaryocytes undergo DNA replication without cell division (polyploidy). Eventually, pieces of their cytoplasm break off to form platelets.

Question 5

What is the lifespan of a platelet and which hormone regulates their production?

Answer 5

Lifespan: ~10 days. Hormone: Thrombopoietin (produced in the liver).

Question 6

What “molecular glue” is required for platelets to adhere to exposed collagen?

Answer 6

von Willebrand Factor (vWF); it binds to both the exposed collagen and the platelet receptors.

Question 6

How does the Vascular Phase reduce blood loss immediately after injury?

Answer 6

Damage triggers neurogenic/myogenic vasoconstriction. It is prolonged by chemicals like Serotonin and Thromboxane A2 (from platelets) and Endothelin-1 (from endothelium).

Question 7

Explain the Positive Feedback Loop in platelet activation.

Answer 7

Activated platelets release ADP and Platelet-Activating Factor (PAF). These factors recruit and activate more platelets, which then release more factors, rapidly growing the plug.

Question 8

Which factors are responsible for Platelet Aggregation specifically?

Answer 8

ADP, PAF, Serotonin, and Thromboxane A2 (TXA_2)

Question 9

How does healthy endothelium prevent accidental clotting?

Answer 9

It secretes Nitric Oxide (NO) and Prostacyclin (PGI_2), which are vasodilators and potent inhibitors of platelet aggregation.

Question 10

Contrast the triggers for the Intrinsic vs. Extrinsic pathways.

Answer 10

Intrinsic (Contact Activation): Triggered by exposure to Collagen (uses proteins already in plasma).
Extrinsic (Cell Injury): Triggered by Tissue Factor (Factor III) exposed by damaged sub-endothelial cells.

Question 11

Describe the “Common Pathway” from Prothrombin to Fibrin mesh.

Answer 11

1. Prothrombinase (Factors Xa, Va, Ca^2+, phospholipids) converts Prothrombin to Thrombin.
2. Thrombin cleaves soluble Fibrinogen into insoluble Fibrin.
3. Factor XIII cross-links fibrin to stabilize the clot.

Note:
Factor X → Factor Xa
- Xa is the active form of factor X (the “a” = activated)
It’s the key enzyme that converts prothrombin → thrombin

Factor V → Factor Va
Va is an activated cofactor
It doesn’t cut anything itself — it helps Xa work faster

Question 12

Which vitamin and ion are essential for the coagulation cascade?

Answer 12

Vitamin K (for synthesizing factors II, VII, IX, X) and Calcium (Ca^2+) (required for almost every step of the cascade).

Question 13

What is coagulation and its main goal?

Answer 13

Coagulation stabilizes the platelet plug by forming a fibrin mesh that creates a durable clot.

Question 14

What enzyme directly converts fibrinogen into fibrin?

Answer 14

Thrombin

Question 15

What is the final stabilized form of the clot?

Answer 15

Cross-linked fibrin, formed by activated factor XIII

Question 16

What triggers the intrinsic (contact activation) pathway?

Answer 16

Exposure of blood to collagen; begins with activation of factor XII.

Question 17

Why is the intrinsic pathway called “intrinsic”?

Answer 17

All required clotting factors are already present in the blood plasma.

Question 18

What triggers the extrinsic pathway?

Answer 18

Exposure of tissue factor (Factor III) from damaged tissues.

Question 19

Which factor starts the extrinsic pathway?

Answer 19

Factor VII, activated by tissue factor (Factor III).

Question 20

Where do the intrinsic and extrinsic pathways converge?

Answer 20

At activation of factor X → Xa.

Question 21

What does factor Xa do in coagulation?

Answer 21

Converts prothrombin into thrombin with help from factor Va and Ca²⁺.

Question 22

What enzyme dissolves fibrin clots?

Answer 22

Plasmin

Question 22

What is the prothrombinase complex?

Answer 22

Xa + Va + Ca²⁺ + phospholipids, which rapidly produces thrombin

Question 23

How is plasmin activated?

Answer 23

Thrombin and tissue plasminogen activator (tPA) convert plasminogen into plasmin.

Question 24

How do heparin and antithrombin III regulate coagulation?

Answer 24

They inhibit active clotting factors IX, X, XI, and XII

Question 25

What is the role of protein C?

Answer 25

Inhibits clotting factors V and VIII.

Question 25

Cell-based theory of coagulation

Answer 25

Involves the idea that platelets are going to play an important role on coagulation + the cells that underlie the endothelial cells in the blood vessels, they're also going to play a role.

Question 26

How does aspirin prevent clot formation?

Answer 26

It inhibits COX enzymes, blocking thromboxane A₂ synthesis and platelet aggregation

Question 27

What happens during the Initiation Phase? - Cell-based theory

Answer 27

Tissue Factor (TF) on fibroblasts/smooth muscle binds to Factor VII, generating a small "Thrombin Spark."

Question 28

What is the goal of the Amplification Phase? - Cell-Based Theory

Answer 28

The "Thrombin Spark" activates platelets and activates factors V, VIII, and XI on the platelet surface to prepare for large-scale production

Question 29

Describe the Propagation Phase and the "Thrombin Burst."

Answer 29

Factors aggregate on the platelet surface to form complexes (Tenase and Prothrombinase), leading to a massive "Thrombin Burst" that creates the final fibrin mesh.

Question 30

How is a clot dissolved after healing is complete?

Answer 30

tPA (Tissue Plasminogen Activator) and Thrombin convert inactive Plasminogen into the active enzyme Plasmin, which "digests" fibrin strands.

Question 31

How do Warfarin (Coumadin) and Aspirin differ in their action?

Answer 31

Warfarin: Blocks Vitamin K (prevents synthesis of clotting factors). Aspirin: Inhibits COX enzymes to prevent Thromboxane A2 synthesis (blocks platelet plug formation).

Question 32

Match the natural anticoagulant to its function: Antithrombin III vs. Protein C.

Answer 32

Antithrombin III: (Works with Heparin) blocks factors IX, X, XI, XII, and Thrombin. Protein C: Inhibits factors V and VIII.

Question 33

Fibrinogen - Factor I

Answer 33

Soluble precursor that becomes the Fibrin "mesh."

Question 34

Prothrombin - Factor II

Answer 34

Becomes Thrombin, the central enzyme of the cascade.

Question 35

Tissue Factor - Factor III

Answer 35

Triggers the Extrinsic pathway when tissue is damaged.

Question 36

Calcium - Factor IV

Answer 36

Essential cofactor for nearly every enzymatic step.

Question 37

Antihemophilic Factor - Factor VIII

Answer 37

Cofactor for the Intrinsic pathway; deficiency = Hemophilia A.

Question 38

Christmas Factor - Factor IX

Answer 38

Enzyme in the Intrinsic pathway; deficiency = Hemophilia B.

Question 39

Stuart-Prower Factor - Factor X

Answer 39

The start of the Common Pathway; activates prothrombin.

Question 40

Hageman Factor - Factor XII

Answer 40

Triggers the Intrinsic pathway via contact with collagen.

Question 41

Fibrin Stabilizing Factor - Factor XIII

Answer 41

Cross-links fibrin strands to make the clot permanent.