Thrombosis - PowerPoint Presentation

Slide1

ThrombosisSlide2

Thrombi

are solid masses or plugs formed in the

circulation from blood constituents. Platelets

and fibrin

form the basic

structure

.

Their

clinical significance

results from

ischaemia

from local vascular

Obstruction

or distant

embolization

.Slide3

Hereditary disorders of

haemostasis

The

prevalence of inherited disorders associated

with increased risk of thrombosis is at least as high

as that of hereditary bleeding disorders

.

A hereditary

thrombophilia

' should be particularly

suspected in

young patients who suffer from spontaneous

thrombosis

,

recurrent deep vein

thromboses

an

unusual

site of

thrombosis

(e.g.

axillary

,

splanchnic

veins,

sagittal

sinus).Slide4

Factor V Leiden gene mutation (activated protein C resistance)

This is the

most common

inherited cause of

an increased

risk of

venous

thrombosis.

It

occurs

in

approximately 4% of

Caucasian

factor V

alleles

Patients

who are heterozygous for factor V

Leiden are

at an approximately 5-8-fold increased risk

of thrombosis

compared to the general population.

Individuals who are homozygous have a

30-140 fold

risk.

Following

venous thrombosis they

have a

higher risk of re-thrombosis compared to

individuals with

deep vein thrombosis (DVT)

but normal

factor V.Slide5

the underlying reason

a

genetic

polymorphism in

the factor V gene (replacement of

arginine

at

position 506 with

glutamine-Arg506Gln)

which makes factor

V less

susceptible to cleavage

by

activated

protein

C

* screening :

polymerase chain

reaction (PCR)

screening

for

the mutation

is relatively simple and the test is

widely performed

.Slide6

Anti-thrombin deficiency

Inheritance

is

autosomal

dominant.

There

are

recurrent venous

thromboses usually

starting in early

adult life

.

Arterial

thrombi

occur occasionally

.

Anti-thrombin

concentrates are available and

are used

to prevent thrombosis during surgery or childbirth

.Slide7

Protein C deficiency

Inheritance

is

autosomal

dominant with variable

Protein C levels in

heterozygotes

are approximately

50% of normal.

Characteristically

,

many patients develop skin necrosis as a result of

dermal vessel occlusion when treated with

warfarin

,

Rarely

, infants may be

born with

homozygous deficiency and characteristically

present with severe disseminated intravascular

coagulation (DIC) or

purpura

fulminans

in infancy.Slide8

Protein S deficiency

The inheritance is

autosomal

dominant.

found in a number

of families

with a thrombotic tendency

.

It

is a

cofactor for

protein C and the clinical features are

similar to

protein C deficiency, including a tendency to

skin necrosis

with

warfarin

therapy. Slide9

Prothrombin

allele G20210A

Prothrombin

allele G20210A is a variant (

prevalence2-3

% in the population) that leads to

increased plasma

prothrombin

levels and increases

thrombotic risk

by at least twofoldSlide10

Hyperhomocysteinaemia

Higher

levels of plasma

homocysteine

may be

genetic or

acquired and are associated with increased

risk for

both venous and arterial thrombosis

.

homocystinuria

is

a rare autosomal recessive

disorder

Vascular disease and thrombosis are major features

of the disease.

Heterozygous present

in approximately 0.5% of

the population

and leads to a moderate increase in

homocysteine

.Slide11

Acquired risk factors

for

hyperhomocysteinaemia

include deficiencies of

folate

, vitamin BI2

or vitamin B6, drugs (e.g.

ciclosporin

), renal

damage

and smoking.

The

levels also increase with age and

are higher in men and post-menopausal femalesSlide12

Hereditary or acquired disorders of

haemostasis

High

factor VIII or fibrinogen levels are also

associated arterial

thrombosis.

The combination of multiple risk factors is

associated with

increased risk of thrombosis.Slide13

Acquired risk factors

Postoperative venous thrombosis

This is more likely to occur in the elderly, obese,

those with a previous or family history of

venous

thrombosis, and in those in whom major

abdominal or

hip operations are

performed

Venous stasis and immobility

These factors are probably responsible for the high

incidence of postoperative venous thrombosis and

for venous thrombosis associated with congestive

cardiac failure, myocardial infarction and varicose

veinsSlide14

Malignancy

Patients with carcinoma of the ovary, brain and

pancreas have a particularly increased risk of

venous thrombosis but there is an increased risk

with all cancers.

The

tumours

produce tissue factor

and a pro-coagulant that directly activates factor X.

Mucin

-secreting

adenocarcinomas

may be associated with DIC

.Slide15

Inflammation

This up-regulates

procoagulant

factors,

down regulates anticoagulant

pathways, particularly

protein C.

Thrombosis

is particularly likely in

inflammatory bowel disease,

Behcet's

disease,

systemic tuberculosis

, systemic

lupus

erythematosusSlide16

Blood disorders

*in patients with

polycythaemia

vera

and

essential

thrombocythaemia

,

the high incidence of thrombosis is due to :

Increased viscosity,

thrombocytosis

,

altered platelet membrane receptors and responses

*There

is a high incidence of

venous thrombosis

in patients

with

sickle cell disease

and patients with

post

splenectomy

thrombocytosisSlide17

Oestrogen

therapy

Oestrogen

therapy, particularly high-dose therapy,

is associated with increased plasma levels of factors

II, VII, VIII, IX and X and

depressed

levels of

antithrombin

and tissue

plasminogen

activator in the

vessel

wall

.

There is a high incidence of postoperative

venous thrombosis in women on high-dose

oestrogen

therapy and full-dose

oestrogen

-containing

oral contraceptives.Slide18

The

antiphospholipid

syndrome

This

may be defined as the occurrence of

thrombosis or

recurrent miscarriage in association with

laboratory evidence

of persistent

antiphospholipid

antibody.

One

antiphospholipid

antibody is the 'lupus

anticoagulant' (LA) which was initially detected in

patients

with SLE,

and

also

found

in other

autoimmune

disorders particularly of

connective

tissues,

lymphoproliferative

diseases,

post-viral infections, with certain drugs including

phenothiazines

and as an 'idiopathic' phenomenon

in otherwise healthy subjects.

it

is associated with venous

and arterial thrombosis. Slide19

Factor IX concentrates

Venous

thrombosis may complicate the use of

factor IX concentrates

which contain trace

amounts

of

activated coagulation

factors. Patients with liver

disease who

are unable to clear these activated factors

are especially at risk.