Basic Principles of Hemostasis

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• Basic Principles of Hemostasis

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• Objectives
• Describe the 4 steps of hemostasis
• Describe platelets, their normal count,
  development, and functions.
• Describe the process of coagulation the role of
  Vit K in it
• Define normal coagulation time
• List the natural anti-coagulants present in blood
• Define hemophilia and list possible symptoms of
  hemophilia
• Explain normal bleeding time and define Purpura

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Steps of Hemostasis

• 1. Vascular spasm (vasoconstriction)
• 2. Platelet plug formation
• 3. Clot formation (blood clotting)
• 4. Clot retraction

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Platelets

• Platelets (Thrombocytes)
• Count 150,000-400, 000 /µL
• Origin megakaryocytes in bone marrow develop
  under influence of Thrombopoeitin
• Disc shape- with vesicles
• 2-4 µ in size
• No nucleus
• Residues of ER, Golgi apparatus
• Mitochondria
• Enzyme systems
• Contain granules which secrete chemicals
• i. Serotonin ii. endothelial growth
• factor iii. Prostaglandins iv.
  phospsholipids (membrane)
• v. Fibrin stabilizing factor
• vi. Platelet Derived Growth factor
• Natural destruction by macrophages in spleen

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• Functions of platelets
• Help in hemostasis (stoppage of bleeding) by
• 1. producing vasoconstriction
• 2. becoming sticky (activated) to form a platelet
  plug to close small holes in blood vessels
• 3. initiate coagulation
• Clinical implications
• Low dose Aspirin reduces platelet adhesiveness
• Rationale for use in blood thinning
• Low platelet count (lt 50,000/µL) causes bleeding
  disorder
• Simple investigation Bleeding time measurement
  by finger prick.
• Normal bleeding time 3-6 minutes
• Disease when platelet count is low
  Thrombocytopenic purpura

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• Vascular spasm
• Contraction of vascular smooth muscle because of
• i. muscle damage ii. serotonin from
  platelets
• Platelet plug formation
• 1. Platelet adhesion to damaged
• endothelium
• 2. Platelet release reaction
• ADP increase platelet
• adhesiveness (stickiness)
• 3. Serotonin TXA2 vasoconstriction
• 4. Platelets stick to one another
• to form a plug Adhesion which is
• good enough to stop a small puncture
• from bleeding
• (Prostacyclin from endothelium
• opposes (?????) stickiness)

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Blood coagulation factors involved
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Principles of Hemostasis
Blood coagulation
Prothrombin activator PROTHROMBINASE) (Factor Xa
Ca Phospholipid Factor V)
Vit K -Source dietary, large intestine
bacteria -Fat soluble -Synthesis of
prothrombin, factors VII, IX, X, Protein C
Prothombin
thrombin
Thrombin Accelerates prothrombinase formation
fibrinogen
fibrin
F XIII
Serum (straw yellow in colour) blood
clotting factors
Clot retraction
RBC clot
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Prothrombinase (Prothrombin activator)
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Breakup/limitation of clot Fibrinolysis
Clot contains Plasminogen
Thrombin, Active Factor XII Tissue plasminogen
activator (pTA)
activate
Plasmin
clot lysis (clot breaks up
Prostacyclin Inhibits platelet adhesiveness
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• Natural anticoagulants
• A. Endothelial surface factors
  B. Anticoagulants present in the blood
  which
• 
  remove THROMBIN
• 
  
• 
  
• 
  
  
• 
  
  
• 
  
  C. Anticoagulants may be used

• 1. Smoothness of endothelial wall
• so has glycocalyx which
• repels clotting factors

• 1. Fibrin itself

• 2. Antithrombin III
• -antithrombin (a globulin)
• heparin
• -removes activated factors
• XII, XI, X
• -removes thrombin

2. Protein C inactivates factors V and VIII
3. Thrombomodulin- a protein bound to
endothelium -combines with thrombin to reduce
clotting.

• In patients
• i. Heparin
• ii. Vit K antagonists
• Outside the body
• Heparin
• Calcium antagonists

4. This combination also activates Protein C
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• Normal coagulation time 3-7 minutes (finger
  prick method)
• Clinical implications
• Coagulation disorders
• i. not enough coagulations
  factors--?
• (Hemophilia (factor
  VIII deficiency)
• transmitted by
  female to males. Only males suffer)
• ii. Not enough Vit K -

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Summary

• Steps of hemostasis
• Platelets and their role in hemostasis
• Normal bleeding time and its abnormality
• Coagulation factors
• The clotting cascade and formation of
  prothrombinase
• Natural anti-coagulation
• Anticoagulation in treatment
• Normal clotting time and abnormalities