Hematopoiesis

Question 1

What special needs do RBCs have?

Answer 1

Need glucose for energy

need NADPH for glutathione reduction

Question 2

Function of 2,3BPG

Answer 2

Modulation of O2-Hb binding

Question 3

Microcytic anemia from

Answer 3

1. Low Fe
2. Lead poisioning
3. thalassemia

Question 4

Macrocytic anemia from

Answer 4

B12 or B9 deficiency (Reduced DNA synthesis)

Question 5

Normocytic anemia from

Answer 5

Low RBC count.

Bleeding, sickle cell, Pyruvate Kinase deficiency, G6PDH deficiency

Question 6

GP1b binds to…

Answer 6

vWF

Question 7

GP1a binds to…

Answer 7

subendothelial collagen

Question 8

Three stages of platelet activation

Answer 8

Adhesion

Aggregation

Activation

Question 9

Aggretation of platelets mediated by what?

Answer 9

GP2b/3a complex, which binds other platelets through fibrin

Question 10

Platelet activation involves what process?

Answer 10

Release of hemostasis chemicals (ADP, Serotonin, TXA2, and vWF) from intracellular granules

Question 11

How does TXA₂ work?

Answer 11

Activates GPCR

Question 12

Prostacyclin function

Answer 12

Vasodilation and inhibitor of aggregation

Question 13

Bernard Soulier syndrome

Answer 13

Deficiency of **GP1b -IX **

Question 14

What are the congenital bleeding disorders listed in lecture?

Answer 14

Bernard-Soulier

Fibrinogen deficiency

Question 15

What is an acquired coag. disorder

Answer 15

Thyombocytopenia

This can happen either by decreased formation of platelets or increased destruction (mediated by antibodies)

Question 16

Plavix. What does it do

Answer 16

Decreases ADP binding to the ADP receptor, which decreases the activation of the GP2b/3a complex.

Question 17

How does Dipyrimadole work?

Answer 17

inhibits Adenosine uptake, Inhibits PDE-3

This increases the plasma Adenosine concentration = which stimulates the A2 receptor = lowers GP2b/3a

Question 18

Factor 2a is…

Answer 18

thrombin

Question 19

factor 1 is

Answer 19

fibrinogen

Question 20

factor 13 is

Answer 20

transglutaminase

Question 21

Fibrin structure

Answer 21

2 tripeptides (abg subunits)

connected via disulfide bridges

Question 22

Prothrombinase complex is made of…

Answer 22

factor 10a and factor 5

Question 23

Function of thrombin

Answer 23

Activation of 5, 7, 8, 13

Question 24

Factor that is the key to starting the intrinsic pathway

Answer 24

factor 8

Question 25

What does hirudin do?

Answer 25

inhibits factor 8

Question 26

Vitamin K function

Answer 26

important for prothrombin (and other factors) forms **gamma**-**carboxyglutamate** residues within **GLA domains** of the factors

Question 27

What does dicoumarol do?

Answer 27

functions as a vitamin K antagonist. Precursors **can't bind to calcium** and can't promote coagulation

Question 28

What factors need vitamin K?

Answer 28

**2, 7, 9, 10**, and **Protein C**

Question 29

Intrinsic initiation

Answer 29

factor 12a binds to **(-) charges** and **prekallekrein** Happens when subendothelial collagen exposure occurs

Question 30

Extrinsic pathway initiation

Answer 30

Due to injury -- Stimulated by **Factor 3** ("Tissue factor")

Question 31

what do you add for aPTT test? What are you testing for?

Answer 31

Phospholipid and Silica This tests for **8,9,11,12** deficiencies (**Hemophilia A** or for **Monitoring Heparin**)

Question 32

What do you add for PTT test? What are you testing for?

Answer 32

Add **factor 3** This test is specific for factor **7, 10 & 2** Used for **monitoring Warfarin**, or testing **Acquired disorders** (Vit. K deficiency, liver disease, liver damage after Tylenol overdose

Question 33

Heparin binds to what? What does this do?

Answer 33

Binds to **Antithrombin 3** This **increases affinity** for thrombin, which **REDUCES clotting**

Question 34

Thrombin binds to what? What does this then do?

Answer 34

**Thrombomodulin** This activates **protein C**

Question 35

How does Protein C work? What does it do?

Answer 35

It works with Protein S to degrade **5a+8a** complex This lowers the production of thrombin (and lowers coagulation)

Question 36

What makes Factor 5 Leiden special?

Answer 36

It is resistant to Protein C (so coagulation is increased)

Question 37

Fibrinolysis is mediated by

Answer 37

Plasmin

Question 38

Describe fibrinolysis

Answer 38

1. Plasminogen binds to fibrin 2. It is converted to its active form by tPA from endothelial cells (kringle domains) 3. Plasmin dissolves clot.

Question 39

What are PAI-1 and PAI-2

Answer 39

_Inhibitors of plasminogen_. They block the function of tPA

Question 40

Hemophilia A Tx?

Answer 40

Human plasma or recombinant factor 8

Question 41

vWF disease?

Answer 41

defective platelet adhesion, so it cant bind to subendothelial collagen More common that hemophilia A.

Question 42

Effects of Antithrombin deficiency

Answer 42

DVT and PE

Question 43

PKD biochemical effects

Answer 43

Low ATP = **Reduced cation gradient**, Low **vitamin K**, Low **H20** Increased hemolytic anemia

Question 44

Why is hemolytic anemia due to PKD less severe? What is the treatment?

Answer 44

**Increased 2,3 BPG** *(from increased 1,3 BPG*) results in increase of oxygen release to tissues Treatment is transfusions and splenectomy