HAEMOPHILIA

BY: Helao Silas

CONTENTS
1. What is hemophilia?
2. Brief History
2.Types
3. Incidence
4. Genetics
5. Clinical presentation
6. Investigations
7. Management
 What is Hemophilia?
Hemophilia is a common hereditary coagulation blood disorder due to deficiency
or reduced activity of clotting factor VIII or clotting factor IX. This disorder is a X-
linked recessive disorder. Hemophilia is a bleeding disorder that slows down the
blood clotting process.
It’s transmitted via females to men who are sufferers.
Female who carry a single mutated gene, are generally asymptomatic and not
affected.
People who have Hemophilia often have longer bleeding after some sort of contact
to injury. People who have severe Hemophilia start to have spontaneous bleeding in
the joints and muscles all around their bodies. Hemophilia is more common in males
than females.
 History of Hemophilia
◦ Best known of the hereditary bleeding disorders since 2nd century AD, (Talmud, Jewish rabbinical
Tradition and Laws manuscripts).
◦ First coined by Schonlein in 1820s.
◦ Originally termed “Haemorraphilia” i.e. love for haemorrhages but over time contracted to
Hemophilia.
◦ Hemophilia is often called the disease of kings, because it was carried by many members of
Europe’s royal families. Queen Victoria I of England was a carrier of haemophilia.

Queen Victoria I
 Inheritance of Hemophilia
◦ Hemophilia A and hemophilia B are inherited in an X-linked recessive pattern. The genes
associated with these conditions are located on the X chromosome, which is one of the two sex
chromosomes. In males (who have only one X chromosome), one changed copy of the gene in
each cell is sufficient to cause the condition. In females (who have two X chromosomes), a
mutation would have to occur in both copies of the gene to cause the disorder. Because it is
unlikely that females will have two changed copies of this gene, it is very rare for females to have
hemophilia. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to
their sons.
◦ In X-linked recessive inheritance, a female with one changed copy of the gene in each cell is called
a carrier. Carrier females have about half the usual amount of clotting factor VIII or clotting factor
IX, which is generally enough for normal blood clotting. However, about 10 percent of carrier
females have less than half the normal amount of one of these clotting factors; these individuals
are at risk for unusual bleeding, particularly after an injury, surgery, or tooth extraction.
Haemophilia Spread Among European Royal
Families
Causes of Haemophilia
 Hemophilia has a sex-linked recessive inheritance.
 In most cases Hemophilia caused by a mutation in a gene that encodes for one of the clotting factors
 Since the hemophilia gene is located on the X chromosome, Hemophilia usually occurs in males, and Female is
the carrier of hemophilia.
Causes of Haephilia
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 TYPES ofTypes:
Haemophilia
Disease Factor deficiency Inheritance
 Hemophilia A- deficiency of clotting factor VIII (X linked recessive)

 Hemophilia B- deficiency of clotting

VIII (8) factors IX (X linked recessive)
Hemophilia A X linked recessive
 Hemophilia C- deficiency of clotting factors XI (Autosomal recessive)

 Parahaemophilia-
Hemophilia B deficiencyIX (9) factor V (Autosomal recessive)
of clotting X linked recessive

Hemophilia C XI (11) Autosomal recessive

Parahemophilia V (5) Autosomal recessive

 Hemophilia A
◦ Also known as classic hemophilia or Factor VIII Deficiency
◦ People with this type of hemophilia have low levels of a blood
clotting factor called figure 8 (FVIII). It’s the most common.

◦ Mild Hemophilia A: Do NOT have spontaneous bleeding but

unusual bleeding occurs with surgery and tooth extractions.
People are usually diagnosed with this in later life.
◦ Moderate Hemophilia A: spontaneous bleeding, delayed oozing
after minor injury, and usually diagnosed before they are 5 to 6
years old.
◦ Severe Hemophilia A: Spontaneous joint or deep muscle
bleeding. Usually diagnosed within first two years of life.
Hemophilia A
 Hemophilia B
◦ Also known as Christmas disease or Factor IX Deficiency
◦ People with this type of hemophilia have low levels of a
blood clotting factor called figure 9 (FIX).

◦ The two different types of hemophilia are caused by

permanent gene changes (mutations). Mutations in the
FVIII gene cause Hemophilia A. Mutations in the FIX gene
cause Hemophilia B.
 Signs and symptoms of Haemophilia
◦ Perpetuated oozing after injuries
◦ repeated bleeding after first bleeding
◦ Easy or spontaneous bruising
◦ Prolonged bleeding
The most frequent symptom for Hemophilia’s types A&B is spontaneous joint bleeding.
COMPLICATIONS OF HAEMPHILIA:
Hemmorrhage in iliopsoas muscles
Joints
Intracranial bleeding
 How is Hemophilia diagnosed?
Hemophilia A&B are diagnosed by measuring factor clotting activity. Individuals who have Hemophilia A
have low factor VIII clotting activity. Individuals who have hemophilia B have low factor IX clotting activity.
Genetic testing is also available for the factor VIII gene and the factor IX gene. Genetic testing of the FVIII
(F8) gene finds a disease-causing mutation in up to 98 percent of individuals who have hemophilia A.
Genetic testing of the FIX gene finds disease-causing mutations in more than 99 percent of individuals who
have hemophilia B. Genetic testing is usually used to identify women who are carriers of a type FVIII or FIX
gene mutation, and to diagnose hemophilia in a fetus during a pregnancy. It is sometimes used to diagnose
individuals who have mild symptoms of hemophilia A or B.
◦ Platelet count: Normal
◦ Bleeding time: Normal
◦ PT: Normal
◦ Clotting time & PTT: Prolonged
◦ Factor VIII or Factor IX assay: Decreased
Normal values for FVIII assays are 50-150%. Values in hemophilia are as follows:
 Mild: >5%
 Moderate: 1-5%
 Severe: <1%
 Management Strategies

◦ Prevention of bleeding episodes.

◦ Replacement therapy.
◦ Gene Therapy
◦ Desmopressin
◦ Other therapies
1. Preventions
Control Bleeding Episodes
• Local measures: apply direct pressure; elevate or ice compress
• Epistaxsis sit up lean forward
Preventions cont…
Prevent joint degeneration
• Immobilize joint during acute bleeding
• Progressive exercise
• Avoid prolong immobility
Avoid contact sports
Avoid IM injections
2. Replacement therapy
◦ Fresh whole blood
◦ Whole plasma
◦ Fresh Frozen Plasma
◦ Cryoprecipitate
◦ Factor VIII or IX Concentrate
◦ Recombinant Factor VII (Novo-Seven): to bypass factor VIII in the coagulation pathway
3. Gene Therapy
4. Desmopressin

Action: stimulates the release of stored factor VIII and

Von Willebrand factor. Von Willebrand factor
carries and binds factor VIII, which then can stay in
the blood stream longer.

-Administration: Injection or Nasal spray.

 5. Other Treatments
EACA (e –amino caproic acid)
Action: Antifibrinolytic  delays clot lysis
Use: Adjuvant therapy for dental procedures
Fibrin Glue:
Action: Contains fibrinogen, thrombin and factor XIII. Placed in the site of injury to stabilize clot.
Use: Dental procedures and after circumcision
Activated Prothrombin complex concentrates
◦ Have increased amounts of activated FVIIa, factor X & thrombin.
◦ APCC are effective even in patients with high titer inhibitors.
◦ risk of thrombosis.
Polyethylene glycol conjugation (Pegylation)
◦ Increases size, decreases renal excretion, extends half life.
Polysialic acid polymers
◦ Forms a “watery cloud” around the target molecule
◦ Biodegradable.
ALWAYS DON’T FORGET…
Thank You For your Attention!!
That

Bleeding for long?

Seek for help immediately!!!

References:
1. Dr Suhasis Mondal “Hemophlia ppt” (Dr R. Ahmed Dental College and Hospital).
2. https://www.slideshare.net/bhatch457/hemophilia (accessed 20 April 2017 at19h00).
3. https://www.cdc.gov/ncbddd/hemophilia/ (accessed 20 April 2017 at 20h00).