Transcript Thrombosis

Thrombosis
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.
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).
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 rethrombosis compared to individuals with deep vein
thrombosis (DVT) but normal factor V.
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.
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.
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.
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.
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 twofold
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.
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 females
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.
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
veins
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.
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
erythematosus
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 thrombocytosis
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.
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.
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.