Transcript Coagulation cascade:

Coagulation cascade:
Hereditary coagulation disorders
Haemophilia A:
Is most common hereditary disorder of blood
coagulation.
The inheritance is: sex linked, but 33% of patients
have no family history & result from spontaneous
mutation.
The incidence: 30-100/106
The defect is: absence or low level of plasma
factor VIII .
The gene for factor VIII is located near the tip of
the long arm of the X chromosome (Xq2.8), the
genetic defects include many deletions &
different point mutations.
Clinical features:
* Recurrent painful haemarthroses & muscle
haematomas dominate the clinical course of
severely affected patients with progressive
deformity &crippling.
*prolonged bleeding occurs after dental
extractions.
*Haematuria is more common than GIT bleeding.
*The clinical severity of the disease is correlate
with the extent of coagulation factor deficiency.
*Spontaneous intracerebral haemorrhage is an
important cause of death in severe disease.
Clinical features:
*Haemophilic pseudotumours: may occur in the
long bones, pelvis, fingers &toes .These result
from repeated subperiosteal haemorrhages with
bone destruction, new bone formation,
expansion of bone pathological fractures.
*many patients have subclinical liver disease & few
have clinical features of chronic hepatitis This is
largely due to many infusions of blood products
& consequence transmission of hepatitis B or C
& other non A non B hepatitis & HIV
transmission
Factor IX deficiency (Christmas
disease, Haemophilia B)
The inheritance & clinical features of Factor IX
deficiency are identical to those of haemophilia
A.
The two disorders are distinguished by specific
coagulation factor assays.
The incidence is 1/5 that of haemophilia A .
The factor IX is coded by gene near to that of
factor VIII (Xq2.6 region).
The factor IX is 1/5 the size of haemophilia A,
As in haemophilia A number of mutations &
deletions have been found.
Von willenbrand's disease:
The incidence: 30-100/106
The inheritance: autosomal dominant with
varying expression.
Pathogenesis:
The primary defect appears to be reduced
synthesis of VWF ,this protein promotes
platelet adhesion & is also the carrier
molecule for factor VIII ,protecting it from
premature destruction & this explain the
reduction of factor VIII level in Von
willenbrand's disease.
The molecular defects that have been
identified include: point mutation & major
deletions.
Clinical feature:
*post operative & post traumatic
hemorrhage, mucosal membrane bleeding
& excessive blood loss from superficial
cuts & abrasions.
*haemarthrosis & muscle haematomas are
rare except in homozygous cases.
Hereditary disorders of other
coagulation factors
All these disorders (deficiency of fibrinogen,
prothrombin, factors V, VII, combined V
and VIII, factors X, XI, XIII) are rare.
In most the inheritance is
autosomal recessive.
Factor XI deficiency
is seen mainly in Ashkenazi Jews and occurs
in either sex.
The bleeding risk is not related to severity of
the deficiency, and is absent from muscles
and joints.
The severity is poorly related to the factor XI
level in plasma.
It usually causes excess bleeding only after
trauma such as surgery, and is treated by
factor XI concentrate or fresh frozen
plasma.
Factor XIII deficiency produces a severe
bleeding tendency,
characteristically with umbilical stump
bleeding.