Coagulation course

( 5 lectures)

1: Haemostasis & role of platelets

2: Haemostasis, role of coagulation proteins
3: Bleeding disorders/ role of platelets & blood
vessels
4: Bleeding disorders due to coagulation defects
5: Thrombophilia
Objectives of Hemostasis Block:
• To acquire a working knowledge of
hemostatic mechanisms
• To understand the basic mechanisms and
clinical characteristics of the most common
acquired and inherited bleeding and
thrombotic diseases
• Learn the common laboratory tests of
hemostasis and their interpretations
• To gain an initial appreciation of the
therapeutic implications of these pathological
conditions
Hemostasis the cessation of blood loss from a
damaged vessel

Hemorrhage = bleeding: can result from

trauma, vascular defects, platelet abnormalities,
or deficiencies of one or more of the plasma
coagulation factors

Thrombosis is a pathologic process in which a

platelet aggregate and/or a fibrin clot forms in
the lumen of an intact blood vessel or in a
chamber of the heart
Normal Hemostasis
 The normal hemostatic
response to vascular damage
depends on closely linked
interaction between the blood
vessel wall, circulating platelets
and blood coagulation factors
 The Hemostatic System

represents a delicate balance between

procoagulant and anticoagulant mechanisms

 Normal

Thrombosis Haemorrhage

Coagulation factors Plasmin Activation

Inhibitors/Regulators Inhibitors/Regulators

AT-III HC-II PAI-1 HRGP

PC PS - antiplasmin

Coagulation Fibrinolysis

HAEMOSTASIS
 The role of vascular wall
Vascular injury generates multiple reactions.
Vessel Injury

Collagen exposure

Platelet release reaction Tissue factor

Serotonin Platelet
phospholipid
Vasoconstriction Thromboxane A2, ADP
Blood
Platelet aggregation Coagulation
cascade
Primary haemostatic plug

Platelet fusion Thrombin

Fibrin
Stable haemostatic plug
 Platelets

Platelets are produced in the bone

marrow by fragmentation of the
cytoplasm of megakaryocytes
( 1 MK 4000 plts)
 Platelets = Thrombocytes

• Lifespan 10 - 12 days
• Function:
hemostasis
 Thrombopoeitin
The major regulator of platelet
production

It is produced by the liver and kidneys

Influenced by the total platelet mass

Platelet Granules
Dense Granules contain:
calcium
ATP, ADP

serotonin

Alpha granules contain:

heparin antagonists
platelet-derived growth factor (PDGF)
vWF, fibrinogen

Lysosomes
Platelet Antigens
Platelets express:

ABO antigens
HLA antigens
Human Platelet Antigens (HPA)
Platelets
Surface glycoproteins (receptors)

Important in platelet reactions of adhesion and

aggregation
Surface glycoproteins (receptors)
Function of platelets

Primary hemostasis

(Platelet plug formation)

 VASCULAR INJURY

Adhesion Exposed
Subendothelium
1-2 sec. ADP,TXA

Aggregation

10-20 sec. Platelet Thrombin

Release

Plug Formation

1-3 min. Fibrin

Formation

Consolidation

3-5 min. Retraction

Fibrin Stablization

5-10 min.

Fibrinolysis
 Function of Platelets

Adhesion

Secretion (release reaction)

Aggregation
 Function of Platelets
• Secretion (release reaction)
Contents of platelets are released

ADP mediates aggregation

Ca++ important for coagulation

Thromboxane A2 is synthesized
 Thromboxane A2

Stimulates platelet aggregation

Causes vasoconstriction
 Laboratory Testing of Platelets

1: Platelet Count (quantitative)

2: Platelet Function (qualitative)

Normal platelet count: 150 – 400 x 109/L