HAEMOSTASIS

Question 1

define Haemostasis

Answer 1

process of arrest of bleeding while maintaining blood in a fluid state within the vascular system.

Question 2

what are the 2 stages of haemostasis

Answer 2

notes

Question 3

platelet formation

Answer 3

notes

Question 4

describe platelets( MCQ)

Answer 4

• Nucleus absent
• Cell membrane : glycoproteins, phospholipids, canalicular system, receptors,
  precursors of various substances.
• Cytoplasm :
  a. ER & golgi apparatus: synthesize enzymes, store Ca.
  b. Mitochondria: ATP & ADP
  c. Contractile proteins: actin, myosin, thrombosthenin
  d. Other proteins present in the cytoplasm are fibrin stabilizing factor, platelet-derived growth factor, Von Willebrand factor.
  e. Granules : clotting factors and platelet-derived growth factor (PDGF).
  f. Enzymes: adenosine triphosphatase and the enzyme necessary for the synthesis of prostaglandins

Question 5

Properties of platelets 3A

Answer 5

1. Adhesiveness : when in contact with any wet surface or rough surface, these are activated and stick to the surface.
   * for adhesiveness- collagen, thrombin, ADP, thromboxane A2, calcium ions and von Willebrand factor.
2. Aggregation- they stick to each other.
   * due to ADP and thromboxane A2.
3. Agglutination. Clumping together
   * due to the actions of fibrinogen and GpIIb-IIIa.

Question 6

Describe the functions of platelets.

Answer 6

1. Haemostasis
   2.clot formation: formation of the intrinsic prothrombin activator
2. Role in clot retraction: Contraction of contractile proteins
3. Role in repair of injured blood vessels: The PDGF - repair of endothelium and other structures of damaged blood vessels.
4. Role in defence mechanism: Phagocytosis of carbon particles, viruses and immune complexes.
5. Transport and storage function: The 5HT is stored in the platelets and transported to the site of injury where it is released.

Question 7

Normal Count and Variations

Answer 7

150,000 -450,000 platelets per microliter of blood. Thrombocytopenia: platelet count less than 150,000 /μl)
* platelet count below 50,000/ μl of blood is called critical count. Thrombocytosis: platelet count > 450,000 platelets/ μl

Question 8

List the various clotting factors.

Answer 8

1- fibrinogen
2- prothrombin
3- thromboplastin
4- calcium
5- labile factor
7-stable factor
8- antihaemophilic factor A
9- christmas factor
10- stuart power factor
11-plasma thromboplastin anticedent
12- hagman factor
13-fibrin stabilising factor

Question 9

Temporary Haemostatic Plug Formation

Platelets Adhesion
Secretion
Aggregation

Answer 9

Endothelial injury and exposure of collagen and (vWF)
|
Platelet adhesions and activation
|
Secretion of (ADP), thromboxane A2 (TXA2), and platelet-activating factor (PAF)
|
Recruitment of additional platelets (aggregation)
|
Hemostatic plug.

Question 10

Mechanism of blood coagulation

Answer 10

1.Rupture of the vessel or damage to the blood itself
2.Complex cascade of chemical reactions -blood coagulation factors.
3.Prothrombin activator.
4.Prothrombin into thrombin.
5.Fibrinogen into fibrin fibers
6.Clot formation

Question 11

common pathway

Answer 11

notes

Question 12

Intrinsic pathway for initiating blood clotting.

Answer 12

n

Question 13

Extrinsic pathway for initiating blood clotting.

Answer 13

n

Question 14

Mechanism of fibrin stabilization.

Answer 14

n

Question 15

Calcium:

Answer 15

Activation of clotting factor II, VII, IX, and X.
Absence of calcium- clotting does not occur

Question 16

Vitamin K :

Answer 16

For the synthesis of following factors. * Coagulant like prothrombin,
* Factors VII, IX and X, and
* Circulatory anticoagulant protein
* Gastrointestinal disease - vit K is not absorbed
* Deficiency of vitamin K, prothrombin time and blood clotting time is prolonged.

Question 17

Blood clot retraction

Answer 17

n

Question 18

Serum =

Answer 18

plasma – clotting factors

Question 19

Fibrinolysis

Answer 19

n

Question 20

Plasminogen activator

Answer 20

• Tissue plasminogen activator (tPA)
  -Predominates under most conditions
• Urokinase plasminogen activator (uPA)
• Released in inflammatory conditions -Extravascular fibrinolysis
• Converts plasminogen into plasmin

Question 21

Plasmin

Answer 21

• Breaks fibrin into fibrin degradation products –clot dissolution
• Degrades fibrin at healthy sites –Prevents unnecessary clot formation * Non-Specific: degrades fibrinogen, prothrombin, factor V, VIII & XII
• Excessive activity- Depletes above clotting factors- hypocoagulability

Question 22

Regulation of fibrinolysis in
Healthy vessels

Answer 22

• Plasminogen activator inhibitor
• PAI-1 -Released from endothelium- predominant
• PAI-2 - Released from placenta – mainly during pregnancy
• Inhibit plasminogen activator- plasmin is not generated.

α2 – Antiplasmin
* Released from liver and kidney
* Inhibit excess plasmin

Question 23

Regulation of fibrinolysis in clot

Answer 23

Fibrin
* Potentiates plasminogen activator – plasmin is generated
* Occupies active site of plasmin- α2 – Antiplasmin cannot inhibit plasmin

Question 24

Why blood does not clot in circulation? (5)

Answer 24

1. smoothness of the endothelial cell surface
   -prevents contact activation of the intrinsic clotting system
2. Glycocalyx on endothelium-repels clotting factors and platelets
3. Thrombomodulin - binds thrombin –slows the clotting process by removing thrombin and activates a plasma protein, protein C, that acts as an anticoagulant by inactivating activated factors V and VIII.
   4.Endothelial cells secrete
   * Prostacyclin
   * NO
   -inhibts platelet aggregation, vasodilation
4. Natural anticoagulants: heparin, antithrombin-III

Question 25

Thrombosis definition

Answer 25

Pathological conditions that can cause intravascular clotting. * The intravascular clotting is called thrombosis and the clot so formed is called thrombus.

Question 26

Predisposing factors and effects of thrombosis

Answer 26

Virchow’s triad Endothelial injury. Alterations in flow of blood Hypercoagulability of blood effects: Ischaemia and infarction. Thromboembolism – Pulmonary and cerebral

Question 27

Anticoagulants

Answer 27

* Anticoagulants refer to the substances which delay or prevent the process of coagulation of blood. In vitro * Substances which sequester calcium, e.g. sodium citrate or oxalate, sodium edetate (EDTA). In vivo * Antagonizing clotting factors (e.g. heparin), * By destruction of the key substance fibrinogen * By inhibiting the synthesis of factors II, VII, IX and X (vitamin-K antagonists).

Question 28

Endogenous anticoagulants/ Circulatory anticoagulants

Answer 28

present inside the blood naturally * Heparin, * Antithrombin III, * Protein-C.

Question 29

Exogenous anticoagulants: administered from outside or are used in vitro

Answer 29

* Heparin, * Calciumsequesters, * Vitamin K antagonist * Defibrination substances

Question 30

Heparin

Answer 30

-Natural, Polysaccharide with sulphate group. -Secreted by Basophils and mast cells. -location: luminal surface of vascular endothelium Mechanism: * Prevents activation of prothrombin to thrombin * Facilitates antithrombin III- deactivate 9,10,11,12

Question 31

Antithrombin III

Answer 31

Present in plasma and vascular endothelium Along with Heparin deactivate Thrombin,9,10,11,12

Question 32

Protein C

Answer 32

n

Question 33

Calcium sequesters or decalcifying agents

Answer 33

Two types 1. Substances which form insoluble salts with calcium: E. g. sodium citrate and sodium oxalate 2. Calcium chelators which bind calcium: E.g. Ethylene diamine tetraacetic acid (EDTA)

Question 34

Vitamin K antagonists.

Answer 34

Mechanism: occupy vitamin K receptor sites in the liver and hinder its activity. Inhibit synthesis of vitamin K-dependent factors- 7,9,10 coumarin derivatives : e.g. dicoumarol, warfarin, phenindione.

Question 35

Defibrination substances.

Answer 35

Mechanism: Destruction of fibrinogen. Malaysian pit viper venom: vivo acts as an anticoagulant by causing defibrination and also by stimulating fibrinolytic system. In vitro, it has a direct anticoagulant effect on fibrinogen by forming imperfect fibrin polymer. Arvin or Ancord.

Question 36

Haemophilia

Answer 36

* Haemophilia A: deficiency of factor VIII (8) * classic hemophilia : 85% * Haemophilia B :deficiency of factor IX. * 15 % * (X) chromosome - Recessive in their inheritance. * Affects men * Women are carriers * Rare in women * Mutation causes 1/3rd cases with no family history * Treatment: Injection of factor VIII or IX.

Question 37

Factor VIII

Answer 37

Large component- Von Willebrand disease Small component- Classic Haemophilia

Question 38

Thrombocytopenic purpura

Answer 38

Thrombocytopenia: presence of very low numbers of platelets in the circulating blood. * tendency to bleed from small venules or capillaries. * small punctate hemorrhages -petechiae, red or purplish blotches

Question 39

major causes of thrombocytopenia purpura

Answer 39

1. Decreased platelet production in the bone marrow due to infections or sepsis, nutrient deficiencies, or myelodysplastic disorders. 2. Peripheral platelet destruction by antibodies. 3. sequestration (pooling) of platelets in the spleen, especially in individuals with portal hypertension and excessively splenomegaly. 4. Consumption of platelets in thrombi. 5. Dilution of the blood from fluid resuscitation or massive transfusion * Idiopathic thrombocytopenia- specific antibodies have formed and react against the platelets to destroy them.

Question 40

Thrombocytopenic purpura Treatment

Answer 40

-fresh whole blood transfusions with large numbers of platelets - splenectomy

Question 41

Blood Coagulation Tests

Answer 41

The prothrombin time indicates the concentration of prothrombin in the blood. * Blood removed from the patient is immediately oxalated- prothrombin cannot change into thrombin. * Large excess of calcium ion and tissue factor is quickly mixed with the oxalated blood. * The excess calcium nullifies the effect of the oxalate, and the tissue factor activates the prothrombin to thrombin reaction by means of the extrinsic clotting pathway. * The time required for coagulation to take place is known as the prothrombin time.