HEMOSOSTASIS COMPONENTS AND STAGES Secondary Hemostasis

o Necessary to control bleeding during trauma, surgery, or dental

procedures
HEMOSOSTASIS
o Components are platelets and coagulation system/plasma proteins
o Derived from the Greek word “Haima” meaning blood and “stasis”
meaning arrest

o a process which causes bleeding to stop Differentiation of Primary and Secondary Hemostasis

o Is a combination of cellular and biochemical events that function in

harmony to keep blood liquid within the veins and arteries

o The first step of wound healing

HAIMA= blood STASIS= arrest

Mechanisms of Hemostasis

 Primary Hemostasis – activated by small injuries to blood vessels.

 Secondary Hemostasis – triggered directly by primary hemostasis

Components of Hemostasis:

1. Vascular System – vasoconstriction

Primary Hemostasis
2. Platelets – primary plug
o Caused by the desquamation of dying or damaged endothelial cells
3. Coagulation Proteins – cross-linked fibrin clot formation
o The blood vessels contract to seal the wound and platelets will fill
4. Fibrinolytic System – removal of clot gradually inorder to restore
the open space to form a plug
blood flow.
o Components are platelets and vascular system
VASCULAR SYSTEM o Tissue Plasminogen Activators (TPAs)
 converts plasminogen to plasmin, activate the fibrinolytic system
A. Blood Vessels

What are the layers of the blood vessels? o Plasminogen activator inihibitor -1
 a regulatory protein for the fibrinolytic system
1. Tunica Adventitia – Consists of connective-tissue fibroblasts and
collagen fibers. o von Willebrand Factor (vWF)

2. Tunica Media – Composed of smooth muscles and connective  protein produced in endothelium and stored in the
tissue, including collagen fibers and occasional fibroblasts. subendothelium, in the form of Weibel- Palade bodies

3. Tunica Intima – Comes into contact with the blood cells and
separates them from a subendothelium composed of a basement
membrane, elastic connective tissue, and collagen fibers. Supports
the endothelium of the blood vessels
B. Endothelium
o Adenosine – Stimulate vasodilation
o ADPase – destroys ADP and limits platelet activation
o Thromboresistance – the resistance of blood vessels to thrombus
formation.

Contains connective tissue and:

o Elastin and Collagen EVESNTS AFTER BLOOD VESSEL INJURY

 Vasoconstriction
 provides permeability to the inner vessel wall
 provides principal stimulus to thrombosis after vessel injury – the first response to injury. (neuroreflex, 5-HT, TXA2, and ET)

o Prostacyclin  Exposure of tissue collagen

– promotes thrombus formation by causing the adhesion of platelets to
 inhibits platelet adhesion and aggregation; the area of injury.
 stimulates vasodilation.
 Exposure of tissue factor (TF, factor III)
o Thrombomodulin – triggers the activation of the extrinsic coagulation pathway.

 Binds and inactivates thrombin  Release of Tissue Plasminogen Activators (TPAs) – initiates fibrinolysis.

o Heparan Sulfate
 coats the endothelial cell surface and weakly enhances activity of
antithrombin-III
PLATELETS
PLATELET PROTEINS/COAGULATION FACTORS
o Also known as thrombocytes
-Are categorized into substrates, cofactors ,and enzymes
o Cytoplasmic Fragments of Megakaryocytes
 Substrates – are the substance which enzymes act.
o Synthesized in the Bone Marrow  Cofactors – accelerate the activities of enzymes that participate in
the coagulation cascade.
o Synthesis is stimulated by the hormone thrombopoietin  Enzymes – are biochemical catalysts.
o The hormone thrombopoietin is also responsible for platelet
Classification of Coagulation Factors:
maturation and release.
o Fibrinogen Group- most labile , have the highest molecular weight, and
o 80% of platelets are in the circulation are consumed during coagulation
o 20% are in the red pulp of the spleen.
Example:
 Factor I
Platelet Functions:
 V
1. Adhesion – Platelet adheres to collagen and changes in shape from  VIII
 XIII
disk to spiny sphere.

2. Aggregation – Platelets adhere to other platelets. o Prothrombin Group- this group is stable and remains preserved in stored
plasma
3. Release – Contents of dense granules are released resulting to
secondary or irreversible aggregation. Example:
 Factor II
 VII
Clot Formation – Platelets release Factor V and expose platelet factor 3,  IX
accelerating coagulation cascade.  X
( dependent on Vitamin K during synthesis )

o Contact Group- Responsible for the activation of fibrinolysis and

complement system

Example:
 Factor XI
 Factor XII
 prekallikrein
 HMWK
 ( participates in the intrinsic pathway)
Coagulation Factors and their functions:
o Factor IX (Plasma Thromboplastin Component)
o Factor I (Fibrinogen) – a component of thromboplastin generating systems.
– is a large globulin protein that functions to be converted into  Deficient in Hemophilia B
insoluble protein and then back to soluble components.  Also known as Christmas Factor

o Factor II (Prothrombin)
– Precursor to thrombin and stimulates platelet aggregation and o Factor X (Stuart-Prower)
activates cofactor protein C and Factor XIII – merges to form conversion of prothrombin to thrombin.

o Factor III (Tissue Thromboplastin, Tissue Factor)
– activates factor VII when blood is exposed to tissue fluids.
o Factor IV (Ionized Calcium)
– is an active form of calcium required for the activation of
thromboplastin and for conversion of prothrombin to thrombin.
o Factor XI (Plasma Thromboplastin Antecedent)
 essential to intrinsic thromboplastin generating of the cascade.
 Occurs more frequently in the Jewish population.
o Factor XII (Hageman Factor)
– a surface contact factor that is activated by collagen.

o Factor V (Proaccelerin, or Labile Factor) o Factor XIII (Fibrin-Stabilizing Factor)

– Consumed during clotting and accelerates the transformation of – stabilizes polymerized fibrin monomerin the initial clot in the
prothrombin and thrombin. presence of Calcium.

o Factor VI – is a non-existent factor

o Factor VII – (Proconvertin, or Stable Factor)

– activated by tissue thromboplastin, which activates factor X

o Factor VIII (Antihemophilic Factor)

VIII/vWF – The entire molecule circulates in the plasma.

Composed of:
 vWF – Glycoprotien responsible for binding to endothelium
and supporting normal platelet adhesion and function; the
carrier for VIII:C

 VIII:C – the active portion which is measured by clotting and is

deficient in hemophilia A.
 COAGULATION PATHWAYS

1.) Extrinsic Pathway Naturally Occuring Coagulation Inhibitors

 Factors involved are III and VII  Antithrombin III
 Initiated by the release of Factor III  Heparin Cofactor II
 Then the Reaction Proceeds to Common Pathway  α2- Macroglobulin
 α1 – Antitrypsin
2.) Intrinsic Pathway  C1 Inhibitor
 Factors involved are VIII,IX,XI,XII, Prekallikrein, and  Proteins C and S
High-Molecular-Weight- Kininogen  Protein C Inhibitor
 All the components are found in the circulating blood.  Tissue Factor Inhibitor Pathway
 Then the reaction enters to the Common Pathway  Plasminogen Activator inhibitor – 1

3.) Common Pathway Naturally Occuring Inhibitors of Fibrinolysis:

 Factors involved are I,II,V,X
 Where the intrinsic and extrinsic pathways merge and where o Plasminogen Activator Inhibitor – 1 (PAI-1)
the stabilization of the soluble fibrin monomer into insoluble o α2 – Antiplasmin
fibrin clot happens. o α2 – Macroglobulin
o α1 – Antitrypsin
o Antithrombin III
o C1 Inhibitor

FIBRINOLYTIC SYSTEM
o The system whereby temporary fibrin clot is systematically and
gradually dissolved as the vessel heals in order to restore normal
blood flow. Summary of Hemostasis
o Plasmin digests fibrin and fibrinogen, resulting in positively reduced
clots.

Coagulation Inhibitors
 Soluble plasma proteins that are natural anticoagulants and are
normally present in the plasma
 Prevents the initiation of the clotting cascade