Hemostasis

Question 1

What is hemostasis?

Answer 1

Formation of a blood clot

Question 2

Where does fibrin come from?

Answer 2

Activated fibrinogen

Question 3

How do you form a fibrin clot?

Answer 3

Thrombin cleaves fibrinopeptides A and B from central globule of fibrinogen. Globular domains at the carboxy terminal end interact with knobs at the amino-terminal ends to form clots

Question 4

Problems of Blood Coagulation

Answer 4

Can lead to harmful obstruction of blood flow

Fibrin formed must be degraded in a timely manner

Question 5

What is the Final Common Pathway?

Answer 5

• Factor Xa converts prothrombin to thrombin (Factor II to IIa)
• Thrombin converts fibrinogen into fibrin and factor XIII into factor XIIIa
• Factor XIIIa, a transglutaminase, stabilizes fibrin by catalyzing formation of covalent cross-links

Question 6

Function: Factor Xa

Answer 6

Converts prothrombin -> thrombin

Question 7

Function: Thrombin

Answer 7

Converts Fibrinogen -> Fibrin

Question 8

Function: Factor XIIIa

Answer 8

Catalyzes formation of cross-links in blood clots

Question 9

What activates the intrinsic pathway?

Answer 9

Contact with certain surfaces

E.g.: Collagen coming into contact with plasma following endothelial damage

Question 10

Intrinsic Pathway Steps

Answer 10

Damaged Surface
Stimulates Kininogen + Kallikrein
XII -> XIIa
XIIa: XI -> XIa
XIa: IX -> IXa
IXa + VIIIa: X -> Xa

Question 11

What activates the extrinsic pathway?

Answer 11

Activated by a tissue factor (tissue thromboplastin) released by injured tissues upon trauma

Question 12

Extrinsic Pathway Steps

Answer 12

Trauma
VII -> VIIa
VIIa releases tissue factors: X -> Xa

Question 13

Function: Tissue Plasminogen Activator

Answer 13

Converts plasminogen -> plasmin

Question 14

tPA only acts on?

Answer 14

Plasminogen physically associated with fibrin

Question 15

Define: Thrombus

Answer 15

Blood clot formed within intravascular space during life

Question 16

Define: Ischemia

Answer 16

Restriction of blood supply

Question 17

Define: Infarction

Answer 17

Necrosis due to ischemia

Question 18

Define: Embolus

Answer 18

Portion of material distinct from blood carried by the bloodstream from one site of body to another

Question 19

What is Virchow’s Triad?

Answer 19

1. Stasis
2. Altered Endothelial Surface
3. Hypercoagulability of Blood

Question 20

[Virchow’s Triad]

What causes stasis?

Answer 20

May be due to hyperviscosity as a result of polycythemia

Usual finding in smokers due to high amounts of CO in the blood, requires production of more RBCs

Question 21

[Virchow’s Triad]

What causes altered endothelial surfaces?

Answer 21

Injury or Endothelial Damage

Question 22

[Virchow’s Triad]

What causes hypercoagulability of blood?

Answer 22

Imbalance between procoagulant and anticoagulant plasma factors

Question 23

[Heparin]

Function

Answer 23

Anticoagulant to prevent thrombosis

It is a glycosaminoglycan

Question 24

[Heparin]

How does it work?

Answer 24

Binds plasma protein antithrombin, inducing conformational changes that enhances inhibitory effect against thrombin and factor Xa

Interferes with the final common pathway

Question 25

[Warfarin] How does it work?

Answer 25

Vitamin K antagonist: blocks synthesis of functional vitamin K-dependent factors II, VII, IX, and X Inhibits posttranslational conversion of glutamate to gamma-carboxyglutamate (for calcium-mediated binding to membrane surfaces) (MEMORIZE mnemonic: 1972, read as “nine-ten- seven[ty]-two”)

Question 26

[Warfarin] How do you treat warfarin toxicity (such as ingestion of Dora Rat Killer)

Answer 26

```  Fresh frozen plasma: contains preformed functional coagulation factors for immediate replacement  Vitamin K: restores capacity for synthesis of functional factors (but factors require some time for synthesis) ```

Question 27

What is the importance of calcium in coagulation?

Answer 27

Calcium plays a role in the attachment of coagulation factors to membranes to form clots. Gamma- carboxyglutamate acts as “handle” for calcium to grab on