Anticoagulation

Question 1

What are 4 steps of hemostasis?

Answer 1

1) vascular spasm
2) formation of PLATELET plug (primary hemostasis)
3) Coagulation and FIBRIN formation (secondary hemostasis)
4) Fibrinolysis

Question 2

What are the three layers of vessel?

Answer 2

1) Tunica Intima
2) Tunica media
3) Tunica externa or adventitia

Question 3

What regulate procoagulants, anticoagulants, and fibrinolytics?

Answer 3

Tunica Intima layer or endothelial cells

Question 4

What substances are considered procoagulants?

Answer 4

1) Coagulation factors (Coagulation)
2) Collagen (Tensile strength)
3) vWF (Platelet adhesion)
4) Fibronectin (cell adhesion)

Question 5

What substances are classified as anticoagulants?

Answer 5

1) Protein S (cofactor for protein C)
2) Protein C (DEGRADES factor 5 and 7 per Nagelhout )
3) antithrombin (Inactivates factors: 2, 9, 10, 11, and 12)
4) Tissue factor inhibitor (inhibit tissue factor)
5) Thrombomodulin (regulate natural occurring anticoagulants)

Question 6

What substances are fibrinolytic?

Answer 6

1) Plasminogen (precursor to plasmin
2) tPA (activate plasmin)
3) Urokinase (activate plasmin)

**Plasmin breaks down Fibrin

Question 7

What are antifibrinolytics?

Answer 7

1) alpha-antiplasmin (Inactivates tPA, urokinase)
2) Plasminogen activator inhibitor (Inhibit plasmin)

Question 8

Vasoconstriction mediators

Answer 8

1) Thromboxane A2
2) ADP
3) Serotonin

ALL three constrict vascular smooth muscle

Question 9

Vasodilation mediators

Answer 9

1) N2O
2) Prostacylin

BOTH vasodilate vascular smooth muscle

Question 10

What is the function of glycocalyx?

Answer 10

-repels clotting factors in the smooth muscle - endothelium

Question 11

what is the function of vWF?

Answer 11

-PLATELET ADHESION

Question 12

what is the function of endothelium?

Answer 12

1) forming barrier separating fluid contents within the blood vessels, RBCs, WBCs, albumin, globulin, fibrinogen, and platelets
2) repels the blood component away from vessel walls –> prevents activation of clotting mechanism
3) suppress activation of the coagulation system by regulating coagulation inhibitors (i.e. TF inhibitors)
4) Nitric oxide and Prostacylin are produced by endothelial cells

Nagelhout p. 895

Question 13

What is the function of Tunica media?

Answer 13

1) Contains collagen –> potent stimulus for platelet attachment
2) extremely thrombogenic
3) contains fibronectin–> cell adhesion (APEX), facilitates anchoring of fibrin during formation of platelet plug (Nagelhout)

Question 14

How does NO affect coagulation?

Answer 14

-Produce by endothelial cells
-L-arginine is converted to NO by nitric oxide synthetase —> activates soluble guanylate cyclase—> producing second messager (cyclic guanosine monophosphate) –> muscle relaxation/dilation –> increase blood flow limits the procoagulant mediators by washing them away
-inhibits platelet adhesion, aggregation, and binding of fibrinogen between glycoprotein 2b/3a
- This whole process occur in the endothelial lining

Question 15

How does prostacylin affect coagulation?

Answer 15

-a lipid molecule produced by endothelial cells from prostaglandin
- interferes with platelet formation and aggregation by vasodilation

Question 16

Platelets

Answer 16

-They are round and disklike–> ciculate freely within the blood
- Formed in the bone marrow from megakaryocytes
- normal count 150,000-300,000/mm3, survive 8-12 days
-Contains mitochondria –> aerobic metabolism
-Have glycogen stores –> anaerobic metabolism
-contain large amounts of calcium and enzymes, can store proteins (vWF, fibrinogen, fibronectin, platelet factor 4, platelet growth factor), and store non-proteins (serotonin, ADP, ATP, histamine, and epi)
-produce THROMBIN (role is activate coagulation factors and to recruit platelets to site injury)
-DO NOT HAVE nucleus, RNA, DNA–> no reproduce

Question 17

How are platelets produced and cleaned up?

Answer 17

-Produced by megakaryocytes in the bone marrow
-cleared by macrophages in the reticuloendothelial system and the spleen