HEMOPHILIA

Introduction

Hemophilia is an inherited disorder in which there is inability to

form an effective clot and hence causes prolonged bleeding in a
patient. It is seen exclusively in males. A person with hemophilia
does not bleed faster, only longer.

Incidence

Hemophilia affects approximately 1 in 5,000 live male births.

Classification:

There are three types of hemophilia - Hemophilia A, Hemophilia B

and Hemophilia C.
Hemophilia A results from deficiency or abnormality of factor VIII
Hemophilia B results from deficiency or abnormality of factor IX
Hemophilia C results from deficiency or abnormality of factor XI

How is hemophilia inherited?

Both are inherited as sex-linked recessive disorder as the genes
responsible for factor VIII & IX are located on the X chromosome.
Females are usually carriers as they have two X-chromosome
and can pass on the defective gene to her offspring.
The following combinations can occur while inheriting hemophilia:

1) Normal Mother + Father with hemophilia.

During each pregnancy, the female offspring has 100% chance

of being a carrier and the male offspring is always normal. Hence,
sons of hemophiliac fathers and normal mothers are normal.
2) Carrier Mother + Normal Father

During each pregnancy, there is 25% chance of a normal

female, 25% chance of a carrier female, 25% chance of a normal
male and 25% chance of an affected male.

3) Carrier Mother + Father with hemophilia

Each pregnancy has 25% chance of a female carrier, 25%

chance a female with hemophilia, 25% chance of a normal male
and 25% chance of an affected male.

4) Mother with hemophilia + Father with hemophilia

During each pregnancy there is 50% chance of an affected

female and a 50% chance of an affected male (actual occurrence
is rare).

5) Mother with Hemophilia + Normal Father

During each pregnancy there is 50% chance of a carrier

female and a 50% chance of an affected male though the actual
occurrence is rare.

Pathophysiology

The normal clotting system consists of

1. Vascular response
2. Platelet adhesion
3. Platelet aggregation
4. Clot formation
5. Clot stabilization
6. Limitation of clot by anticoagulation
7. Fibrinolysis to reestablish vascular patency
Coagulation cascade consists of two pathways - the intrinsic and
extrinsic pathway. It is the deficiency of factor VIII or IX in the
intrinsic pathway that causes hemophilia.

Clinical presentation

Mild hemophilia patients (factor levels>5% and <50%) bleed

only after injury, invasive procedure or surgery. Carriers of
hemophilia are also sometimes found to have factor levels in the
Mild range.

Moderate hemophiliacs (factor levels - 2to 5%) experience more

bleeds, about once a month, usually after trauma, surgery or
extreme exertion. They usually bleed in the muscles and joints.
Once a bleeding occurs in a particular area, these patients may
continue to have bleeding episodes in those areas.

Severe hemophiliacs (factor level<1%) bleed spontaneously

usually in joints, muscles and soft tissues.

Joint and muscle bleeding may cause pain, tingling, heat,

swelling, limited range of motion etc. It commonly occurs in the
ankles, elbows and knees but can also affect any joint in the body.

Rarely, bleeding can occur in mucous membranes such as the

mouth, tongue, throat, nose etc.
Hematuria may also occur.
Central nervous system bleeds such as intracranial or spinal cord
Other sites where major bleeds may occur is neck, throat, eye, GI
system, hip, testes, retroperitoneum and following severe injury.

Investigation
Prolonged PTT (Prothrombin thromboplastin time) with a normal
PT (Prothrombin time) and normal bleeding time is suggestive of
hemophilia. It is confirmed by doing the factor assay.

Treatment:

Replacement of the deficient factor in the blood is the mainstay

of the therapy. Factor concentrates are available in nominal
values of 250, 500 and 1000 IU.

Factor concentrates available are :-

1. Human factor VIII concentrates - They are plasma -derived

Factor VIII concentrates made from pooled plasma from
thousands of donors.
2. Recombinant Factor VIII concentrates - They are made by
recombinant technique and also contain albumin.
3. Porcine Factor VIII concentrates - They are used in patients
with inhibitors of Human Factor VIII. They do not transmit
Hepatitis or HIV. Recipients may have occasional allergic
reactions.
4. Prothrombin Complex Concentrate (PCC, Factor IX
Complex)- It contains a concentrate of Prothrombin, Factor IX
and X. Activated forms of factor VII, IX and X are also present.
PCC is widely used to treat bleeding in patients with inhibitors
to factor VIII. It is also in therapy for Hemophilia B. However, it
may cause thrombosis and there is a risk of myocardial
infarction.
5. Coagulation Factor IX concentrates - It is the product of
choice for patients with Hemophilia B. It is a human plasma
derived factor.
6. Anti- inhibitor Coagulant complex (AICC) – Used for patients
with inhibitors to factor VIII.
7. Recombinant factor IX concentrate – It is still in clinical trial.
8. Cryoprecipitate – One bag consists of 80 U of factor VIII and
VWF & 200-300mg of fibrinogen. However factor VIII content
varies from bag to bag and no infant should be treated with
less than 2-3 bags. It is used to treat Von-Willebrand disease,
Hemophilia. A or fibrinogen deficiencies if there is no
alternative.

Other agents used to increase the factor levels in the blood

1. Desmopressin (DDAVP) – It is a synthetic analogue of natural

vasopressin, which causes immediate release of factor VIII. It is
given intravenously in a dose of 0.3 mg/kg diluted in 50ml
saline and infused over 15-30 minutes. The drug can also be
injected into the subcutaneous tissue. Intranasal spray is also
now available.
2. Estrogen – Progesterone – In high doses (10mg /day), they
may raise plasma levels of factor VIII and IX after several
weeks and also reduce endometrial proliferation. They are
given to women with factor VIII or IX deficiency to treat
menorrhagia or to raise factor levels before surgery.

There are various treatment regimes available :

1) Demand therapy :- Infusion of a factor at the time of a

bleed.

2) Prophylaxis: - Patient receives infusions at regular intervals

to maintain a functional level of factor in the blood at all times.

3) Continuous infusion: - It is usually given before or after

elective surgery or after major trauma.

How are the joints protected in hemophiliacs?

In hemophiliacs, joint bleeding and re-bleeding is common.

Bleeding into joints cause inflammation of the synovium. With
repeated hemorrhages, chronic synovitis may ensue leading to
proliferation of the inflamed vascular synovial membrane causing
rebleeding.

Chronic synovitis - It presents with effusion commonly in the

knee causing a swollen, boggy and warm joint.
Concentrate prophylaxis for 2-4 weeks plus 1-2 weeks course of
oral prednisone (0 .5 mg/ kg/ d) should be tried. While
concentrate is being given, the strength of the adjacent muscles
should be improved with isometric and other exercises. Posterior
splints should be worn at night to avoid injury during sleep.

It the above measures fail, synovectomy should be considered.

Flexion contractures- it is commonly seen at the elbow and the

knee. At the elbow, an enlarged radial head often impedes
forearm rotation. Excision of the radial head may prove to be
beneficial. Knee flexion contractures can be treated with cylinder
casts around the thigh and calf.

What are other therapies available for hemophilia?

Gene therapy for hemophilia A and B is being tried in animal

studies.

How can Hemophilia be detected prenatally?

Chorionic villus biopsy at 8 weeks gestation on amniocentesis at

12-14 weeks can be used for prenatal diagnosis by DNA analysis
If DNA analysis is not available, fetal blood can be aspirated at
18-20 weeks gestation. If pure fetal blood is obtained, factor VIII
activity can be assayed. If fetal blood mixed with amniotic fluid is
obtained, factor VIII: Ag can be measured.

How are carriers detected?

Most carriers have a factor VIII level between 30-70 U/dl. These
women should be treated the same way as male hemophiliac with
similar factor levels.

Nursing Care:
1. Avoid IM injection
2. Safety during transfusion
3. Prevention of injury
4. Avoid Aspirin
5. Exercise
6. Pain management
7. Genetic Counselling