Disorders of inherited Clotting

Factors
Prepared by
Dr Hodan Jama
DM
Common inherited coagulation disorder
The most common inherited coagulation
disorder are
Von willebran disease
Hemophillia A and B
Factor X1 deficiency
Fibrinagen disorder
Rare inherited coagulation disorder

Deficience of factors
XIII
X
VII
V
II
VII
and V
Vk dependent factors
Etiology.

Hereditary deficiencies of most procoagulant

proteins lead to bleeding
The genes for factor 8 and factor 9 are on the X
chromosome
 Whereas virtually all the other clotting factors
are coded on autosomal chromosomes
 Factor 8 and factor 9 deficiencies are the most
common severe inherited bleeding disorders
 Von Willebrand disease is the most common
congenital bleeding disorder
Procoagulant proteins, low levels of the
so-called contact factors
◦ prekallikrein
◦ high-molecular-weight kininogen
◦ Hageman factor factor 12
 Cause a prolonged activated partial
thromboplastin time but are not associated
with a predisposition to bleeding.
Haemophila
Inherited Bleeding Disorder

Factor VIII/FIX deficiency

X-Linked Inheritance
◦ Carrier XX may have low levels

Spontaneous mutation
Hemophilia

Etiology
 Hemophilia A factor 8 deficiency occurs
in 1 in 5000 males
 Hemophilia B factor 9 deficiency occurs
in approximately 1 in 25,000
Clinically the two disorders are
indistinguishable other than by their
therapy
The lack of factor 8 or factor 9 delays the
generation of thrombin, which is crucial
to forming a normal,
 functional fibrin clot and solidifying the
platelet plug that has formed in areas of
vascular injury.
 The severity of the disorder is
determined by the degree of clotting
factor deficiency.
Clinical Manifestations.
Patientswith less than 1%
severe hemophilia factor 8 or factor 9 may have
◦ spontaneous bleeding or
◦ bleeding with minor trauma
 Patients
with 1% to 5%
moderate hemophilia factor 8 or factor 9 usually require
◦ moderate trauma to induce bleeding episodes.
In mild hemophilia >5% factor 8 or factor 9, significant
trauma is necessary to induce bleeding;
◦ spontaneous bleeding does not occur.

Bleeding problems in Haemophilia
Factor Level Type of Bleed

<1% Spontaneous/severe

2%-5% Mild trauma/ occasionally

spontaneous
>5% Trauma/Surgery
Mild hemophilia may go undiagnosed for
many years,
 Whereas severe hemophilia manifests in
infancy when the child reaches the toddler
stage
 In severe hemophilia, spontaneous
bleeding occurs, usually in the muscles or
joints (hemarthroses).
Laboratory Investigations

Prolonged PTT – corrects on mixing with

normal plasma.
Normal PT
Normal TT
Normal platelet count
Factor VIIIc level-decreased
Factor VIIIAg-Absent in severe
Haemophilia A
to determine the appropriate factor
replacement therapy.
 Prenatal diagnosis and carrier diagnosis
are possible using
◦ molecular techniques.
Haemophilia B

Less common than Haemophilia A

Due to Factor IX deficiency
Inherited in X-linked recessive manner 
Clinical Features
Same as for Haemophilia A
Laboratory Diagnosis

Prolonged PTT – corrects with mixing

with normal plasma
Normal PT
Factor IX levels – decreased
Treatment
Factor IX concentrate
Fresh frozen plasma
Treatment
 Early, appropriate replacement therapy is
the hallmark of
◦ excellent hemophilia care
 Acute bleeding episodes are best treated
◦ in the home when the patient has attained
◦ the appropriate age and the parents have
learned home treatment
Bleeding associated with
◦ surgery
◦ trauma
◦ Dental extraction often can be anticipated
Excessive bleeding can be prevented with
appropriate replacement therapy
At the time of bleeding – depends on whether bleed is :
minor bleed or
major bleed
Minor Bleed
Includes some joint bleeding (non-critical), dressing
changes, removal of sutures
Mild Haemophilia – Give DDAVP
Factor VIII concentrate
Cryoprecipitate
Dose depends on severity of deficiency and body weight
– single dose of replacement is usually adequate.
Major Bleed
Life threatening bleed
Bleeds into important sites (CNS)
Post surgery
Loading dose followed by Q8H doses
until risk has passed
Factor VIII levels should be measured
Use of Factor concentrates is preferable
In between bleeds
Immunization especially Hepatitis B
Proper dental care
Advise about appropriate physical activities
Counselling for risk of infections
Encourage attendance at school
Education about recognition and prompt
treatment of bleeds
Prophylaxis
Prophylactic

Therapy starting in infancy has greatly

diminished the likelihood of chronic
arthropathy in children with hemophilia
 For life-threatening bleeding, levels of 80%
to 100% of normal factor 8 or factor 9 are
necessary
 For mild to moderate bleeding episodes
(hemarthroses), a 40% level for factor 8 or a
30% to 40% level for factor 9 is appropriate.
Desmopressin
Desmopressin acetate is a synthetic
vasopressin analog with minimal
vasopressor effect
 Desmopressin triples or quadruples the
initial factor 8 level of a patient with mild
or moderate hemophilia A
◦ but has no effect on factor 9 levels
Patientstreated with older factor 8 or 9
concentrates derived from
◦ large pools of plasma donors were at high risk for
hepatitis B, C, and D and HIV
Inhibitors are IgG antibodies directed against
transfused factor 8 or factor 9 in congenitally
deficient patients
Inhibitors arise in 15% of severe factor 8
hemophiliacs but are less common in factor 9
hemophiliacs
For low titer inhibitors, options include
continuous factor 8 infusions.
 For high titer inhibitors, it is usually
necessary to administer a product that
bypasses the inhibitor, preferably
recombinant factor 7a.
Activated prothrombin complex
concentrates, used in the past to treat
inhibitor patients
 paradoxically increased the risks of
thrombosis resulting in fatal
complications, such as myocardial
infraction
For long-term treatment of inhibitor patients
 induction of immune tolerance by
◦ repeated infusion of the deficient factor with or
without immunosuppression may be beneficial.
Early institution of factor replacement and
continuous prophylaxis
◦ beginning in early childhood should prevent the
chronic joint disease associated with hemophilia
Factor XI (11) deficiency
People with factor XI (11) deficiency, also
called hemophilia C
 have low levels of factor XI
Factor XI is not as critical to clotting as other
factors, a person with factor XI deficiency
may still need treatment and attention
Bleeding in people with factor XI deficiency
is sometimes affected by other factors or may
be apparent only with surgery
symptoms

Bleeding in people with factor XI deficiency is not

predictable or related specifically to the factor level.
Spontaneous bleeding is very rare.
 common signs and symptoms, such as:
◦ Bleeding after injury in the mouth or nose
◦ Blood in the urine
◦ Bleeding after surgery, especially
◦  tonsillectomy,
 sinus surgery, dental work
 menstrual bleeding and
 bleeding related to childbirth
diagnosed

Factor XI deficiency is diagnosed after

finding screening tests that identify
prolonged activated partial thromboplastin
time (aPTT) then by following up to
determine that factor XI activity is lower
than normal. These results should be
confirmed by a specialized health care
provide
Treatment
Treatment is necessary for
 traumatic bleeding
Surgery
bleeding related to pregnancy.
There are no specific factor XI
 Other hemostatic agents have been
studied that can help the blood to clot.
Fibrinagen disorder

Absence of cerculating fibrinogen due to

rare inherited autosomal ressive condition
Afibriogemia may be associated with
Bleeding
 obstetric complication
and rarely thrombosis