HEMOSTASIS

HEMOSTASIS

It is the arrest of blood loss from
damaged vessels and is essential to
life

HEMOSTASIS

Physical trauma to the vascular
system causes

vasoconstriction

and

initiates series of interactions
between

platelets

endothelial cells

and

the

coagulation cascade

Formation of a hemostatic

plug

Damage to vessel exposes

collagen of sub-endothelium

Platelet adhesion and release of

granules

Platelet aggregation and activation

factors in plasma

THROMBOSIS

It is a pathological condition resulting
from inappropriate activation of
haemostatic mechanisms.

VENOUS THROMBOSIS

Usually associated with stasis of
blood;
Venous thrombus has a small platelet
component and a large component of
fibrin

ARTERIAL THROMBOSIS

Usually associated with
atherosclerosis;
Arterial thrombus has a large platelet
component

Drugs affect haemostasis

and thrombosis

By affecting:

•

Blood coagulation (fibrin formation)

•

Platelet function

•

Fibrin removal (fibrynolysis)

DRUG AFFECTING BLOOD

PLATELET INHIBITORS

ANTICOAGULANTS

THROMBOLYTIC AGENTS

DRUG AFFECTING BLOOD

PLATELET INHIBITORS

Aspirin

Clopidogrel

Ticlopidine

Glycoprotein IIb/IIIa

Receptor Antagonists

ANTIPLATELET DRUGS –

ASPIRIN

•

Inactivates constitutive form of

cyclooxygenase

(COX-1), the key enzyme

which takes part in synthesis among other

thromboxane

(TXA

) in platelet from

arachidonic acid

•

TXA

promotes aggregation

•

Suppression of platelet aggregation last to

the end of platelet’s life (7-10 days)

ANTIPLATELET DRUGS –

ASPIRIN

•

Daily recommended dose is 75-100mg

•

Clinical uses:

•

prophylactic treatment of transient

ischemic atacks (TIA)

•

Reduction of the incidence of myocardial

infarction

•

decrease mortality in postmyocardial

infarction patients

ANTIPLATELET DRUGS –

ASPIRIN

•

Unwanted effects:

•

Bleeding time is prolonged

•

Increased incidence of hemorrhagic

stroke

•

Increased incidence of gastrointestinal

bleeding (ulcer)

ANTIPLATELET DRUGS –

TICLOPIDINE

•

It inhibits ADP-dependent aggregation of the

platelet

•

Decreases the incidence of thrombotic stroke

•

Clinical uses:

•

For patients who cannot tolerate Aspirin

•

Unwanted effects:

•

Prolonged bleedings

•

Neutropenia

ANTIPLATELET DRUGS –

CLOPIDOGREL

•

It is analog of ticlopidine

•

Also inhibits ADP-induced aggregation

•

It is more effective than Aspirin

•

It is recommended for patients before PTCA

•

The main unwanted effect is bleeding

•

It can inhibit cytochrom P-450 so it may interfere

with metabolism of other drugs (warfarin or
fluvastatin)

ANTIPLATELET DRUGS –

antagonists of GP IIb/IIIa

receptors

•

ABCIXIMAB a monoconal antibody

•

TIROFIBAN oligopeptid

ANTIPLATELET DRUGS –

antagonists of GP IIb/IIIa

receptors

•

They inhibit all pathways of platelet

activation

•

By binding to GP IIb/IIIa receptor they

block the binding of fibrynogen and other
factor and aggregation does not occur

ANTIPLATELET DRUGS –

antagonists of GP IIb/IIIa

receptors

•

They are used intravenously for single

administration

•

CLINICAL USES:

•

in high-risk patients undergoing coronary angioplasty

to reduce the risk of restenosis

•

UNWANTED EFFECTS:

•

potencial of bleeding

•

immunogenicity

DRUG AFFECTING BLOOD

ANTICOAGULANTS

HEPARIN

ENOXAPRIN

VITAMIN K

ANTAGONISTS

WARFARIN

ACENOCOUMAROL

CLINICAL USE OF

ANTICOAGULANTS

They are used for prevention of:

•

Deep vein thrombosis

•

Extension of established deep vein
thrombosis or recurrence of
pulmonary embolus

•

Thrombosis and embolisation in
patients with atrial fibrillation

CLINICAL USE OF

ANTICOAGULANTS

•

Thrombosis on prosthetic heart valves

•

Cardiac events in patients with
unstable coronary syndromes

•

Cotting in extracorporeal circulations
(haemodialysis or bypass surgery)

HEPARIN

•

It is not a single substance but a family of

mucopolysaccharides

•

It is present with histamine in the

granules of mast cells

HEPARIN

•

Inhibits coagulation by activating

antithrombin III, which inhibits thrombin
(IIa) , factor Xa and other serine proteases
by binding to the active site

HEPARIN

•

Is given intravenously or subcutaneously

•

The activated partial thromboplastin time

(APTT) must be measured
(targed range 1,5-2,5 times control)

HEPARIN

ADVERSE EFFECTS

•

Hemorrhage

•

Hypersensitivity reactions: chills, fever

and even anaphylactic shock

•

Thrombocytopenia (after 8-10 days of

treatment)

ENOXAPRIN

It is one of low-molecular-weight heparins
(LMWHs);
It is fractionated heparin

ENOXAPRIN

•

Increase the action of antithrombin III on

factor Xa

•

Does not act on thrombin

•

Has a longer elimination half-time than

heparin

•

Does not prolong the APTT

ORAL ANTICOAGULANTS -

WARFARIN

•

Warfarin has structual similarity to

vitamin K

•

Inhibits activation of factors II, VII, IX, X,

which are depend on present of vitamin K

ORAL ANTICOAGULANTS -

WARFARIN

•

Pharmacological effect is delayed, it can

occur about 48 hours after first
administration

•

The effect must be monitored by

measuring INR (target range 2-3)

•

Dose are given indyvidualised according

to INR

ORAL ANTICOAGULANTS -

WARFARIN

ADVERSE EFFECTS

•

Hemorrhage and bleeding

•

Cause abortion

•

It is teratogenic agent

WARFARIN - interactions

Increased effect



Amiodarone



Ciprofloxacin



Metronidazole



Some of NSAIDs



Sulfonamides

Decreased effect



Vitamin K



Barbiturates

DRUG AFFECTING BLOOD

THROMBOLYTIC AGENTS

ALTEPLASE

STREPTOKINASE

THROMBOLYTIC DRUGS

CLINICAL USES:



Acute myocardial infarction within 12
hours of onset
THE EARLIER THE BETTER!



Acute thrombotic stroke within 3
hours of onset (in selected patients)



Acute arterial thromboembolism



Clearing arterial shunts and cannulae

THROMBOLYTIC DRUGS

STREPTOKINASE



Is a protein extracted from culture of
streptococci



Activates free plasminogen to convert
to plasmin, which in turn cleaves
fibrin, thus lysing thrombi

THROMBOLYTIC DRUGS

STREPTOKINASE

ADVERSE EFFECTS



Bleeding disorders



Hypersensivity – rashes, fever,
anaphylactic shock

THROMBOLYTIC DRUGS

STREPTOKINASE

Drug does not act in patients who
have circulating antibodies against
streptokinase (in case streptococcal
infection);
they may neutralize its fibrynolytic
effect

THROMBOLYTIC DRUGS

Alteplase

Known as tissue-type plasminogen

activator (tPA)

•

Is a serine protease from cultured
human mellanoma cells

•

Activates only plasminogen bound to
fibrin in a thrombus or a hemostatic
plug („fibrin selective”)

THROMBOLYTIC DRUGS

Alteplase (tPA)

ADVERSE EFFECTS

•

BLEEDING complication
(gastrointestinal and cerebral
hemorrhages)

Document Outline