L3: Natural anti-coagulants & fibrinolysis

Question 1

What are the factors that contribute to blood fluidity?

Answer 1

Endothelial surface factors and blood factors

Question 2

What are the endothelial surface factors that contribute to blood fluidity?

Answer 2

“Smooth glycocalyx and thrombomodulin”

1) The smoothness of the endothelial surface: prevent contact activation of the intrinsic system.
2) Presence of a layer of glycocalyx (mucopolysaccharide) on the endothelium: repels clotting factors and platelets, thereby preventing activation of clotting process.

3) Presence of Thrombomodulin:
- a protein bound with the endothelial membrane which binds thrombin.

• the thrombomodulin thrombin complex activates a plasma protein called Protein-C, that inactivates activated factor V and VIII.

Question 3

What are the blood factors that contribute to blood fluidity?

Answer 3

“Adsorption of antithrombin III and heparin to the fibrinolytic system”

1) Adsorption of about 85 to 90% of the thrombin formed from prothrombin to the fibrin threads this prevents excess spread of the clot.
2) Antithrombin III: The thrombin that does not adsorb to the fibrin “the remaining 15%” threads soon combines with antithrombin III, which further blocks the effects of thrombin, then inactivates it.

3) Heparin:
- A powerful anticoagulant that produced mainly by mast cells and small amounts formed by blood basophil cells.
- The heparin secreting mast cells are abundant in tissues surrounding lungs & liver.

4) The presence of fibrinolytic system that continuously removes small clots

Question 4

What is the action of heparin?

Answer 4

• Heparin by itself, has little or no anticoagulant property.
• It acts as cofactor for anti-thrombin III. When it combines with antithrombin III, the effectiveness of anti-thrombin III in removing thrombin increases about 100-1000 times.
• Also, the heparin–antithrombin complex removes several other activated coagulation factors e.g., factor XII, XI, IX and X.

Question 5

What is the definition of plasminogen (profibrinolysin)?

Answer 5

is one of plasma proteins present in an inactive form and when activated it is converted to plasmin (or fibrinolysin).

Question 6

What is the definition of plasmin?

Answer 6

• A proteolytic enzyme that digests the fibrin threads as well as other coagulant factors as fibrinogen, factor V, factor VIII, prothrombin, and factor XII.
• Plasmin can cause complete lysis of the blood clot.

Question 7

What activates plasminogen into plasmin?

Answer 7

This occurs via a group of substances called plasminogen activators.

They include:

1) Tissue plasminogen activator (t-PA)
2) Other plasminogen activators

Question 8

Mentions the steps of the activation of tissue plasminogen activator

Answer 8

• When a clot is formed, a large amount of plasminogen is trapped in the clot along with other plasma proteins.
• The injured tissues and vascular endothelium very slowly release a powerful activator called tissue plasminogen activator that eventually converts plasminogen to plasmin few days after the clot has stopped the bleeding.
  “Unlike tissue thromboplastin which is secreted quicker”
• The formed plasmin in turn removes the remaining blood clot.

Question 9

Mention examples for other plasminogen activators

Answer 9

• Thrombin and active factor XII.
• Urokinase: it prevents the formation of blood clots in the urinary tract.
• Streptokinase: derived from certain types of bacteria known as haemolytic streptococci and is used for treatment of early acute myocardial infarction to dissolve the clot.

Question 10

What does the liver produce “relating to hemostasis” and what inactivates it?

Answer 10

• The liver produces a t-PA inhibitor called antiplasmin that inhibit the t- PA and delays the fibrinolysis.
• The protein-C inactivates this inhibitor and consequently stimulates fibrinolysis. “As well as inactivation of factor five and factor eight’

Question 11

What are the significance of fibrinolysis?

Answer 11

“SUMIIIII”

S: Many Small blood vessels in which the blood flow has been blocked by clots are reopened by fibrinolysis.

U: It prevents the blood clotting inside the Urinary tract “urokinase” and prevents clotting of the menstrual blood.

MI: The stimulation of fibrinolysis is used clinically in early management of acute Myocardial Infarction. This is accomplished either by intravenous injection of t-PA or injection of Streptokinase or urokinase locally in the clot via a cardiac catheter.

Question 12

What is the definition of Anticoagulants?

Answer 12

These are the substances used to prevent blood clotting.

Question 13

What is the classification of Anticoagulants?

Answer 13

A) In vitro anticoagulants “prevent intrinsic”

B) In vivo anticoagulants

Question 14

how are blood samples collected without clotting?

Answer 14

1) Collecting blood in smooth bags lined with silicone.
2) Precipitation of calcium by citrate.
3) Addition of heparin.
4) Addition of EDTA (ethylene – diamine tetra-acetic acid). It chelates the Ca2+ in the blood.

Question 15

What is the definition of in vitro anticoagulants?

Answer 15

Are used to prevent clotting outside the body.

Question 16

What is the definition of in vivo anticoagulants?

Answer 16

Are used to prevent clotting inside the body.

Question 17

what are examples of in vivo anticoagulants?

Answer 17

Heparin

Coumarin derivatives as dicumaroul & warfarin

Question 18

What is heparin? And what forms it?

Answer 18

It is a naturally occurring anticoagulant used in the treatment of intra-vascular thrombosis, It is formed by mast cells and basophil leucocytes.

Question 19

What antagonizes the action of heparin?

Answer 19

The action of heparin (acidic) can be neutralized by adding protamine (basic protein) which forms an irreversible complex with heparin.

Question 20

What is the action of coumarin derivatives like dicumarol and warfarin?

Answer 20

They inhibit the action of vitamin K in the liver through competitive inhibition with subsequent decreased synthesis of factors II, VII, IX, and X as well as protein C.

Question 21

Compare between Heparin and dicumarol acc to:

Origin
Mode of action
Site of action
Route of administration
Onset
Duration
Antidote

Answer 21

Origin: Mast cells and basophils - Plant

Mode of action:
-Activates antithrombin III thereby inactivating thrombin, factors IX, X and XI

-Competitive inhibition with vit. K in liver, so it inhibits the formation of prothrombin, factors VII, IX & X.

Site of action: in vivo and in vitro - only in vivo

Route of administration: I.V or I.M. “May cause hematoma” - oral

Onset: Rapid - slow

Duration: short “should be repeated” - long

Antidote: Protamine sulphate 1% + Fresh blood transfusion - Vit K

Question 22

What are in vitro Anticoagulants?

Answer 22

In vitro anticoagulants :
• Ca++ → deionization by citrate. → Precipitation by oxalate. → Chelation of Ca++ by EDTA

• Collecting of blood in ‘‘unwettable’’ silicone coated tubes , that prevent activation of factor XII.
• Addition of heparin.

Question 23

What are the disorders of Hemostasis ?

Answer 23

A) Conditions that cause excessive bleeding.

1. Purpura
2. Vitamin K deficiency
3. Hemophilia: deficiency of factors VIII, IX, or X

B) Conditions that cause excessive intra vascular clotting.

Question 24

What is the nature of hemophilia?

Answer 24

• It is a congenital sex linked; recessive disease carried on X chromosome.
• It is carried by females and manifested always in males.

Question 25

What causes hemophilia?

Answer 25

Deficiency of factor VIII, IX, or XI. So, there are three types of hemophilia.

Question 26

What are the types of hemophilia and what causes each one?

Answer 26

-Hemophilia A:
 Is the classic hemophilia.
 It is caused by deficiency of factor VIII and represents 85% of cases of hemophilia.

-Hemophilia B:
 Is due to absence of factor IX.

-Hemophilia C:
 Is due to absence of factor XI.

Question 27

What is hemophilia characterized by?

Answer 27

-Hemophilia is characterized by:
 Excessive bleeding after mild trauma.
 Whole blood coagulation is prolonged.