HEMOSTASIS

WHAT IS HEMOSTASIS?
the stoppage of blood flow
Keeps blood fluid in the circulation and then, when an injury occurs,
produces a clot to stop the bleeding, keeps the clot confined to the site of
injury, and, finally, dissolves the clot as the wound heals.
Thrombosis (clotting)
Hemorrhage (bleeding)

THREE HEMOSTATIC
COMPONENTS
Extravascular component
Vascular component
Intravascular component

EXTRAVASCULAR COMPONENT
Provides back pressure on the injured vessel through swelling and the
trapping of escaped blood.
The ability of the surrounding tissues to aid in hemostasis depends on the
following factors:
The bulk or amount of surrounding tissue.
The type of tissue surrounding the injured vessel
The tone of surrounding tissue.

VASCULAR AND INTRAVASCULAR

COMPONENTS
Vascular Components: vessels
Role played by vessels depends on:
Size
Amount of smooth muscles within their walls
Integrity of the endothelial cell lining

Intravascular hemostasis: platelets and pro-coagulants in the plasma

Components are involved in:
Coagulation
Fibrinolysis

CONCEPTS OF NORMAL HEMOSTASIS,

HYPOCOAGULATION, AND
HYPERCOAGULATION
Coagulation - process by which blood changes from a liquid to a gel,
forming a clot
Normal Hemostatic Balance

Thrombos
is

s
el
ss
Ve

Coagulatio
n

Ve
ss
el
s

Platelet
s

Body

Fibrinolys
is
Bleeding

HYPOCOAGULATION AND
HYPERCOAGULATION
Hypocoagulation - can be inherited or acquired
Inherited:
Hemophilia well known inherited hypo-coagulable disorder
Classic Hemophilia (Type a) caused by factor VIII deficiency

Acquired:
Disseminated Intravascular Coagulation (DIC)
Liver and Kidney Disease

Hypercoagulation associated with inappropriate formation of thrombi in

the vasculature that occlude normal blood flow

HISTORY BACKGROUND OF
HEMOSTASIS
Aristotle and Plato
2nd A.D. - Hemophilia; love of hemorrhage
12th century Moses Maimonides
1803 published the clinical descriptions of families with the haemophilia
disorder. The disorder was given the name hemophilia, which means
love of hemorrhage by Schnlein
1828 disorder was first describes as hemophilia in a thesis by Hopf

OVERVIEW OF THE HEMOSTATIC

MECHANISM
Primary Hemostasis involves the vascular and platelet response to
vessel injury
Secondary Hemostasis includes the coagulation process to such injury

BASIC SEQUENCE OF EVENTS IN PRIMARY AND

SECONDARY HEMOSTASIS AFTER VESSEL
INJURY
Events

Comments

Step 1

Vasoconstriction

Controlled by vessel smooth muscle;

enhanced by chemicals secreted by
platelets

Step 2

Platelet Adhesion

Adhesion to exposed subendothelial

connective tissue

Step 3

Platelet Aggrefation

Interaction and adhesion of platelets

to one another to form initial plug at
injury site

Step 4

Fibrin-Platelet Plug Formation

Coagulation factors interact on

platelet surface to produce fibrin;
fibrin-platelet plug then forms at site
of vessel injury

Step 5

Fibrin Stabilization

Fibrin clot must be stabilized by

coagulation factor XIII

ROLE OF COAGULATION
Process whereby, on vessel injury, plasma proteins, tissue factors, and
calcium interact on the surface of platelets to form a fibrin clot
14 factors
Serine Proteases- activate other specific factors in the coagulation
sequence
Three coagulation pathway
Extrinsic Pathway
Intrinsic Pathway
Common Pathway

ANTITHROMBOTIC, FIBRINOLYTIC, AND

COAGULANT SUBSTANCES RELEASED FROM OR
FOUND ON THE SURFACE OF INTACT
ENDOTHELIAL CELLS
SUBSTANCE

ACTION

HEMOSTATIC ROLE

Prostacyclin (PGI2)

Inhibits platelet activation

Stimulates vasodilation

Anticoagulant
Reduced blood flow rate

Adenosine

Stimulates vasodilation

Reduces blood flow rate

Thrombomodulin

Endothelial surface receptor for thrombin

Binds and inactivated thrombin and enhances
anticoagulant and fibrinolytic action of protein C
found in the plasma

Anticoagulant
Fibrinolytic

Heparin sulfate

Coats the endothelial cell surface and weakly

enhances activity of antithrombin-III, a plasma
anticoagulant

Anticoagulant

Tissue Plasminogen
Activator (tPA)

Converts plasminogen to plasmin

Fibrinolytic

von Willebrand
factor (vWF)

Required for platelet adhesion to site of vessel

injury

Coagulation

COAGULATION FACTOR NOMENCLATURE

WITH PREFERRED NAMES AND SYNONYMS
NUMERAL

PREFERRED NAME

SYNONYMS

Fibrinogen

II

Prothrombin

Prethrombin

III

Tissue Factor

Tissue Thromboplastin

IV

Calcium

Proaccelerin

Labile Factor
Accelerator Globulin

VII

Proconvertin

Stable Factor
Serum Prothrombin Conversion Accelerator
(SPCA)

VIII:C

Anti-Hemophilic
Factor (AHF)

Anti-hemophilic Globulin (AHG)

Anti-hemophilic Factor A
Platelet Cofactor 1

COAGULATION FACTOR NOMENCLATURE

WITH PREFERRED NAMES AND SYNONYMS
NUMERA
L

PREFERRED NAME

SYNONYMS

IX

Plasma Thromboplastin Component

(PTC)

Christmas Factor
Anti-hemophilic Factor B
Platelet Cofactor 2

Stuart-Prower Factor

Stuart Factor
Prower Factor
Auto-prothrombin III

XI

Plasma Thromboplastin Antecedent

Anti-hemophilic Factor C

XII

Hageman Factor

Glass Factor
Contact Factor

XIII

Fibrin Stabilizing Factor

Laki-Lorand Factor
Fibrinase
Plasma Transglutaminase
Fibrinoligase

COAGULATION FACTOR NOMENCLATURE

WITH PREFERRED NAMES AND SYNONYMS

NUMERAL

PREFERRED NAME

SYNONYMS

Prekallikrein

Fletcher Factor

High-Molecular-Weight Kininogen
(HMWK)

Fitzgerald Factor
Contact Activation Factor
Williams Factor
Flaujeac Factor

EXTRINSIC PATHWAY
Activated by the release of tissue thromboplastin into the plasma from
injured tissue cells
Factor III
Factor VII

INTRINSIC PATHWAY
Occurs when a vessel is injured, exposing the subendothelial basement
membrane and collagen, both surfaces that promote coagulation

Factor
Factor
Factor
Factor

XII
XI
IX
VIII

COMMON PATHWAY
Begins with activation of factor X to factor Xa, by either intrinsic or the
extrinsic factor.

Factor
Factor
Factor
Factor

X-V
II
I
XIII

ROLE OF PLATELETS IN HEMOSTASIS

(HISTORY OF CLINICAL RECOGNITION AND

INVESTIGATION)

1842 described platelets by several investigators

1878 recognized that platelets are unique elements of the blood
1940 platelet structure using the electron microscope
150 400 X 109 / L normal value for platelets

Quantitation of platelet numbers performed since the early part of the

20th century using a hemocytometer, microscope and stain specific for
platelets
1950 phase contrast microscopy

ROLE OF PLATELETS IN HEMOSTASIS

(HISTORY OF CLINICAL RECOGNITION AND

INVESTIGATION)

Qualitative (functional) platelet evaluation first available with the

introduction of the bleeding time test by Duke
Prolonged bleeding time:

thrombocytopenia

thrombocytopathy

Bleeding time best screening test for platelet function

ROLE OF PLATELETS IN HEMOSTASIS

(PLATELET MORPHOLOGY AND FUNCTION IN

HEMOSTASIS)

Smallest microscopically visible element

2 to 4 micrometer in diameter
7 fL in volume
Light violet-purple granular appearance
9-10 days
Roles in hemostasis:

Adhere to injured vessels

Aggregate at the injury site
Promote coagulation on their phospholipid surface
Release biological chemicals important to hemostasis
Induce clot retraction

SUBSTANCES SECRETED BY
PLATELETS
Dense Granules (or dense bodies)

ADP
Calcium
Serotonin
ATP
Pyrophosphate

SUBSTANCES SECRETED BY
PLATELETS
Alpha Granules

HMWK
Fibrinogen
Factor V
Factor VIII:vWF
Factor Platelet 4
Thrombospondin
Platelet-Derived Growth Factor
Beta Thromboglobulin
Plasminogen
A2-Antiplasmin
Cl Esterase Inhibitor

 Summary of Most Important Substances Secreted by

Platelets and Their Role in Hemostasis
SUMMARY OF MOST IMPORTANT SUBSTANCES SECRETED
BY PLATELETS AND THEIR ROLE IN HEMOSTASIS

Role in
Hemostasis

Substances

Source

Comments on Principle
Function

Promote
Coagulation

HMWK

Alpha Granules

Fibrinogen
Factor V
Factor VIII:vWF

Alpha Granules
Alpha Granules
Alpha Granules

Contact activation of intrinsic

coagulation pathway
Convert to fibrin for clot formation
Cofactor in fibrin clot formation
Assists platelet adhesion to
subendothelium to provide
coagulation surface

Provide
aggregation

ADP
Calcium
Platelet Factor 4
Thrombospondin

Dense Bodies
Dense Bodies
Alpha Granules
Alpha Granules

Promotes Platelet Aggregation

Same
Same
Same

Promotes
Vasoconstriction

Serotonin

Dense Bodies

Thromboxane A2
precursors

Membrane
Phospholipids

Promotes vasoconstriction at injury

site
Same

SUMMARY OF MOST IMPORTANT SUBSTANCES SECRETED

BY PLATELETS AND THEIR ROLE IN HEMOSTASIS

Role in
Hemostasis

Substances

Source

Comments on Principle
Function

Platelet-Derived
Growth Factor
Beta
Thromboglobulin

Alpha Granules

Alpha Granules

Plasminogen

Alpha Granules

A2-Antiplasmin
Cl Esterase
Inhibitor

Alpha Granules
Alpha Granules

Promote Vascular
Repair

Other systems
affected

Promotes smooth muscle growth for

vessel repair
Chemotactic for fibroblasts to help in
vascular repair
Precursor to plasmin, which induces
clot lysis
Plasmin inhibitor; inhibits clot lysis
Complement system inhibitor

PLATELET INDUCTION OF CLOT

RETRACTION
Last act of platelets within a platelet-fibrin clot
Needs: ATP, Calcium

Can be observed in vitro when blood clots in a test tube

The retraction process involves stabilization of platelet-platelet and
platelet-fibrin attachments. The pulling forces are provided by contractile
platelet elements in a process similar to muscle tissue contraction.
Purpose of clot retraction:
Participation in the vascular constrictive response to injury
Stabilization of the fibrin clot network
Debulking of the clot to help re-establish blood flow

FIBRINOLYSIS IN
HEMOSTASIS
History of Investigation
1700 John Hunter
- Unexplained finding that blood from people who had died in accidents or while in some
traumatic situation did not clot.
1937 MacFarlane
- damaged tissues release a substance (plasminogen activator) that activated the inert
precursor called plasminogen, which normally circulates in the plasma, to its active form, plasmin.
Plasmin a nonspecific proteolytic enzyme capable of degrading fibrin as well as
fibrinogen and factors V and VIII.

FIBRINOLYSIS IN
HEMOSTASIS

Function of Fibrinolysis in Hemostasis

System whereby the temporary fibrin clot is systematically and gradually

dissolved as the vessel heals in order to restore normal blood flow
Responsible for fibrinolysis:

Plasmin
Tissue plasminogen activator
Fibrin Degradation (Split) Products (FDP or FSP)
Protein C and S enhances fibrinolysis and inactivate tPA inhibitors

BASIC TERMINOLOGY FOR CLINICAL

FINDINGS IN BLEEDING DISORDERS
Petechiae purplish red, pinpoint haemorrhagic spots in the skin caused
by loss of capillary ability to withstand normal blood pressure and trauma.
Purpura produced by haemorrhage of blood into small areas of skin,
mucous membranes, and other tissues
Ecchymosis form of purpura in which blood escapes into larger areas of
skin or mucous membrane, but not into deep tissue
Epistaxis nosebleed
Hemarthosis leakage of blood into a joint cavity
Hematemesis vomiting of blood

BASIC TERMINOLOGY FOR CLINICAL

FINDINGS IN BLEEDING DISORDERS
Hematoma swelling or tumor in the tissues or a body cavity that
contains clotted blood
Hematuria intact red cells in the urine
Hemoglobinuria Hb (no intact red cells) in the urine
Hemoptysis expectoration of blood secondary to haemorrhage in the
larynx, trachea, bronchi, or lungs
Melena stool containing dark red or black blood
Menorrhagia excessive menstrual bleeding