Hemophilia
Contents
• Clotting and clotting factors
• Hemophilia
• Hemophilia A and Hemophilia B
OBJECTIVE
At the
end of the PDF Notes, the students will be able to
• Explain hemophilia
• Describe the pathophysiology and
clinical features of Hemophilia
• Describe the clinical features and
treatment of Haemophilia a and Haemophilia b
Hemophilia
Normal Clotting
Response to
vessle injury
1.
Vasoconstriction to reduce blood flow
2. Platelet
plug formation (von willebrand factor binds damaged vessle and platelets)
3.
Activation of clotting cascade with generation of fibrin clot formation
4.
Fibrinlysis (clot breakdown)
Clotting Cascade
Normally
the ingredients, called factors, act like a row of dominoes toppling against
each other to create a chain reaction.
If one of the factors is missing this chain reaction cannot proceed.
Hemophilia
Hemophilia is an inherited bleeding disorder in which there
is a deficiency or lack of factor VIII (hemophilia A) or factor IX (hemophilia
B)
COAGULATION DISORDERS: Disorders of plasma coagulation
factors may have hereditary or acquired origin
HEREDITARY COAGULATION DISORDERS
1) Classic haemophilia or haemophilia A
(due to inherited deficiency of factor VIII) sex-(X)- linked disorders
2) Christmas disease or haemophilia B (due to
inherited deficiency of factor IX).
Types of Bleeding Disorders
• Hemophilia
A (factor VIII deficiency)
• Hemophilia
B (factor IX deficiency)
• von
Willebrand Disease (vWD)
• Other
Inheritance of Hemophilia
• Hemophilia
A and B are X-linked recessive disorders
• Hemophilia
is typically expressed in males and carried by females
• Severity
level is consistent between family members
• ~30
% of cases of hemophilia are new mutations
Haemophilia A
• It is the second most common
hereditary coagulation disorder next to von Willebrand’s disease occurring due
to deficiency or reduced activity of factor VIII (anti-haemophilic factor).
• Inherited as a sex-(X-) linked
recessive trait- manifest in males
• The frequency of haemophilia varies
in different races, the highest incidence being in populations of Britain,
Northern Europe and Australia.
Pathogenesis of Haemophilia A
• Haemophilia A is caused by
quantitative reduction of factor VIII in 90% of cases, while 10% cases have
normal or increased level of factor VIII with reduced activity
• Factor VIII synthesised hepatic parenchymal cells activate
factor X (intrinsic coagulation pathway)
• Factor VIII-vWF complex
• 25% factor VIII level may develop
bleeding, most symptomatic haemophilic patients have factor VIII levels below
5%.
Clinical Features of Haemophilia A
• Patients of haemophilia suffer from
bleeding for hours or days after the injury.
TREATMENT
• Factor VIII replacement therapy,
Christmas Disease (Haemophilia B)
• Inherited deficiency of factor IX
(Christmas factor or plasma thromboplastin component) produces Christmas
disease or haemophilia B.
• TREATMENT. Therapy in symptomatic haemophilia B
consists of infusion of either fresh frozen plasma or a plasma enriched with
factor IX
Haemophilia Inheritance FVIII and FIX only
•
Two
chromosomes determine the sex of an individual, X and Y.
•
Female
XX
•
Male
XY
Father with Haemophilia
•
Genetic
defect causing haemophilia on that part of X chromosome not on Y chromosone
•
Daughter
of haemophiliac will inherit his X and be carrier.
•
Sons
of a haemophiliac will not be affected as they inherit fathers Y chromosome
which does not carry FVIII or FIX gene.
Carrier Mother (one normal gene and one defective gene)
•
Chances
carrier mother passing defective gene to a child are 50:50.
•
Each
daughter has 50:50 chance being a carrier
•
Each
son has 50:50 chance of having haemophilia.
Spontaneous Mutation
In some 30%
cases of haemophilia there is no known family history
Haemophilia
is probably the result of spontaneous genetic mutation in these families.
Summary
HEREDITARY COAGULATION DISORDERS
• Classic haemophilia or haemophilia A
(due to inherited
deficiency of factor VIII) sex-(X)- linked disorders and Christmas disease or haemophilia B (due
to inherited deficiency of factor IX
• Hemophilia
A and B are X-linked recessive disorders
• Hemophilia
is typically expressed in males and carried by females
• Haemophilia A is caused by
quantitative reduction of factor VIII in 90% of cases, while 10% cases have
normal or increased level of factor VIII with reduced activity
• Factor VIII replacement therapy
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