Hemophilia is perhaps the most well-known inherited bleeding disorder, although it is relatively rare. It affects mostly males. Many more people are affected by von Willebrand disease, the most common inherited bleeding disorder in America caused by clotting proteins.

1. Hereditary coagulation
disorders

2. • Hereditary deficiencies of each of the
coagulation factors have been described. But
we are going to discuss today:
• Haemophilia A (factor VIII deficiency),
• Haemophilia B (Christmas disease, factor IX
deficiency)

3. Haemophilia A
• Haemophilia A is the most common of the
hereditary clotting factor deficiencies.
• The prevalence is of the order of 30–100
per million population.
• The inheritance is sex‐linked but up to
one‐third of patients have no family history
and these cases result from recent mutation

4. Molecular genetics
The factor VIII gene is situated near the tip of
the long arm of the X chromosome. It is
extremely large.
The defect is an absence or low level of
plasma factor VIII.
Approximately half of the patients have
missense
or frameshift mutations or
deletions in the factor VIII gene

5. Clinical features
• Infants may develop profuse post‐circumcision
haemorrhage
• excessive bruising when they start to be active.
• Recurrent painful haemarthroses and muscle
haematomas dominate the clinical course of
severely affected patients and, if inadequately
treated, lead to progressive joint deformity and
disability
• Local pressure can cause entrapment neuropathy
or ischaemic necrosis.
• Prolonged bleeding occurs after dental extractions.

6. • Spontaneous haematuria and gastrointestinal
haemorrhage,.
• The clinical severity of the disease correlates inversely
with the factor VIII level .
• Operative and post‐traumatic haemorrhage are
life‐threatening both in severely and mildly affected
patients.
• Although not common, spontaneous intracerebral
haemorrhage occurs more frequently than in the
general population and is an important cause of death
in patients with severe disease

8. Laboratory findings
The following tests are abnormal:
1 Activated partial thromboplastin time
(APTT).
2 Factor VIII clotting assay.
The platelet function analysis‐100 (PFA‐100)
and prothrombin
time (PT) are normal

9. Treatment
• Bleeding episodes are treated with factor VIII
replacement therapy,
• and spontaneous bleeding is usually controlled
if the patient’s factor VIII level is raised to 30–
50% of normal.
• 1‐Diamino‐8‐D‐arginine vasopressin (DDAVP;
desmopressin)provides an alternative means
of increasing the plasma factor VIII level in
milder haemophiliacs.
• Local supportive measures used in treating
haemarthroses and haematomas include
resting the affected part, application
of ice and the prevention of further trauma.

10. Inhibitors
• One of the most serious complications of
haemophilia is the development of antibodies
(inhibitors) to infused factor VIII which occurs in
30–40% of severely effected patients, usually
within the first 50 days of exposure.
• This renders the patient refractory to further
replacement therapy
• Recombinant activated factor VII (VIIa)
and activated prothrombin complex concentrates
(FEIBA –factor VIII inhibitor bypassing activity) can
be useful in the treatment of bleeding episodes.

11. • Factor VIIa complexes with tissue factor exposed at
the site of injury and produces local haemostasis.
The process is independent of factor VIII or IX and
is not affected by their inhibitors.
• Factor VIIa has a short half‐life and therefore
frequent doses may be needed

12. Factor IX deficiency (haemophilia B,
Christmas disease)
• The inheritance and clinical features of factor IX
deficiency (Christmas disease, haemophilia B) are
identical to those of haemophilia A.
• Indeed, the two disorders can only be distinguished
by specific coagulation factor assays. The incidence is
one‐fifth that of haemophilia A.
• Factor IX is coded by a gene close to the gene for factor
VIII near the tip of the long arm of the X chromosome.
• Its synthesis is vitamin K‐dependent.

13. • The principles of replacement therapy
are similar to those of haemophilia A.
Bleeding episodes are
treated with high‐purity factor IX
concentrates.
Because of its longer biological half‐life,
infusions do not have to be given
as frequently as do factor VIII concentrates
in haemophilia A

14. Laboratory findings
The following tests are abnormal:
1 APTT;
2 Factor IX clotting assay.
As in haemophilia A, the PFA‐100 and PT
tests are normal