Study THIS Coagulation section:

Question 1

Describe the origin of platelets

Answer 1

a. Pinched off cytoplasmic inclusion from megakaryocytes – no nucleus
b. Synthesis is under the influence of thrombopoietin
c. Life span of 10 days

Question 2

List and describe the functions of platelets

Answer 2

a. Main function is in coagulation process
- release thromboxane A2 and aggregate at site of tissue injury to form a platelet plug to stop blood loss
- Release heparin neutralizing factor – this enhances clot formation

Question 3

describe the three major steps of hemostasis

Answer 3

• *a. Vascular spasm –> vasoconstriction
• Can be caused by:
  1. Myogenic contraction
  2. Nervous reflex
  3. Local humoral factors – platelets release Thromboxane A2 –> vasoconstriction
• *b. Formation of Platelet Plug
  i. Platelets bind to exposed collagen at injury site –> become activated
  1. Platelete (GP1b-IX-V) binds to von Willebrand factor which causes adherance by binding to collagen
  ii. Platelets activated by ADP, release thromboxane A2 –> increases platelet aggregation –> increases release of thromboxane A2 –> increased platelet adherence
  iii. Fibrinogen induced platelet aggregation
  1. Platelet glycoprotein IIb/IIIa receptor binds fibrinogen and promote aggregation of platelets
  2. Can be blocked by different drugs: plavix – inhibits ADP/ platelet aggregation
  iv. Platelet plug formed, platelets release heparin neutralizing factor.
• *c. Blood coagulation
  i. Blood transformed from liquid to gel by
  1. Transforming fibrinogen (from liver) to fibrin
  2. Stabilizing fibrin meshwork (coagulation factor XIII)
  3. Strengthening platelet plug

Question 4

Describe the three major stages of coagulation

Answer 4

a. Stage I – Development of the Prothrombin Activator Complex
i. Intrinsic pathway: (TEEN)
1. Hageman factor (XII) activated (XIIa) by contact with collagen
2. This activates factor XI
3. Activated factor XI in the presence of Ca++ activates factor IX
4. Activate IX in the presence of Ca++, platelet phospholipids, and activated factor VIII (activated by thrombin)  activates factor X
ii. Extrinsic pathway
1. Activated factor VII bound to tissue factor (III) in presence of Ca++ activates factor X
2. VII activated by: IXa or Xa from intrinsic pathway; Xa or thrombin
b. Stage II: Conversion of Prothrombin to Thrombin
i. Done by prothrombin activator complex (Xa, Va, and platelet phospholipids) in presence of Ca++
ii. Prothrombin then converted to thrombin
c. Stage III – conversion of fibrinogen to fibrin, clot formation and retraction
i. Thrombin converts fibrinogen into fibrin monomers which then form fibrin fibers
ii. Thrombin and Ca++ activate factor XIII which crosslinks the fibrin fibers

Question 5

Describe the role of plasminogen and plasmin in clot dissolution (tissue plasminogen activator)

Answer 5

a. Plasminogen is the precursor to plasmin
i. Converted to Plasmin by Tissue Plasminogen activator (tPA)
b. Plasmin breaks down the fibrin in the clot
c. This is done as fibroblasts form a scar

Question 6

Describe the role of the vascular wall integrity in anticoagulation. What are the anticlotting roles of endothelial cells?

Answer 6

a. Intact walls have a smooth texture that prevent platelet aggregation
b. Endothelial cells:
i. Synthesize and release prostacycline (PGI2) –> inhibits platelet aggregation
1. Also is a vasodilator
ii. Release endothelium derived relaxing factor (NO) –> vasodilation
iii. Secrete tissue factor pathway inhibitor –> binds to tissue factor/factor VIIa complexes
iv. Endothelial cell receptor – thrombomodulin binds thrombin
1. Complex then binds to protein C and activates it
2. Protein C inactivates factors Va and VIIa
c. Plasma proteins
i. Antithrombin III activated by Heparin –> inactivates thrombin

Question 7

factor VIII is what?

Answer 7

Antihemophiliac factor

• Antihemophilic factor (AHF) or antihemophilic globulin (AHG) or antihemophilic factor A
• Factor VIII circulates in the blood stream bound to von Willebrand factor
• lacking this factor = haemophilia

Question 8

factor XII is what?

Answer 8

hageman factor

• binds collagen and platelet
• helps keep factor VIII around longer since it binds it

Question 9

factor II is what?

Answer 9

prothrombin

Question 10

Which factors are vitamin K dependent?

Answer 10

a. Factor II – Prothrombin
b. Factor VII
c. Factor IX – Christmas Factor
d. Factor X
e. Protein C and Protein S

Question 11

Tissue plasminogen activators (t-PA)

Answer 11

dissolves clots, role in limiting damage in heart attacks and strokes

Question 12

Heparin

Answer 12

Enhances antithrombin III for clot dissolving

i. Low amount present in blood; can be administered as drug

Question 13

Prostacyclin (prostglandin I2)

Answer 13

inhibits platelet aggregation; vasodilator

Question 14

Factor XIII

Answer 14

(fibrin-stabilizing factor)

Question 15

Antithrombin III –

Answer 15

plasma protein that inactivates thrombin; enhanced by heparin

Question 16

Protein C –

Answer 16

Inactivate factors Va and VIIIa

i. Protein S is cofactor

Question 17

Protein S –

Answer 17

Inactivate factors Va and VIIIa; works with protein C

Question 18

Tissue factor (factor III) –

Answer 18

Binds factor VIIa to activate factor X

Question 19

Von Willebrand factor –

Answer 19

Binds to collagen at site of injury then to glycoprotein GP Ib-IX-V on platelet surface to effect platelet aggregation

Question 20

Platelet glycoprotein IIb/IIIa receptor –

Answer 20

binds fibrinogen to facilitate platelet aggregation

Question 21

Heparin neutralizing factor (platelet factor 4) –

Answer 21

released by platelets to enhance clot formation by limiting effects of heparin

Question 22

What is the cause of classic hemophilia or hemophilia A

Answer 22

a. All forms of hemophilia are caused by a deficiency in an INTRINSIC Pathway Factor
b. Hemophilia A
i. Defective functioning of factor VIII (antihemophiliac factor)
ii. Gene for factor VIII on the X chromosome, so this is predominantly a male disease

Question 23

What is the cause of hemophilia B (or Christmas disease)

Answer 23

a. Deficiency of factor IX (also called Christmas factor)

b. Gene for this factor on the X chromosome, so this is predominantly a male disease (only one copy of the gene)

Question 24

Be able to give the main way thrombin is removed from the blood

Answer 24

a. Antithrombin-Heparin binds thrombin → Inactivates thrombin
b. Heparin can be administered as an anticoagulant drug
- can bind thrombomodulin to be removed

Question 25

HEMOSTASIS definition

Answer 25

Arrest of Bleeding or prevention of blood loss after a blood vessel is injured

Question 26

Thromboxane A2

Answer 26

• cyclooxygenase transforms membrane arachidonic acid into a prostaglandin which in turn is transformed by thromboxane synthase into thromboxane A2
• vasoconstrictor
• released by activated platelets to recruit other platelets
• decreases blood flow which makes clot formation more likely

Question 27

Thrombomodulin

Answer 27

-binds thrombin

Question 28

Briefly explain the interactions between thrombin, thrombomodulin, Protein C, Protein S, Factor V (and Factor V Leiden) and Factor VIII.

Answer 28

Endothelial cell receptor, thrombomodulin binds thrombin. This complex then binds to Protein C and activates it. Protein C (in combination with Protein S) inactivates Factors Va and VIIIa.