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