Haemophilia a Done)

8/3/2019 Haemophilia a Done)

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BY

AZHANI ABDUL RAHMAN

FATIN NADZIRAH BINTI MOHAMAD IDRIS

INTAN SUZANA BINTI HASSANIZYAN SYAZNI ABD RAZAK

SITI NAQIUYAH TAN FARRIZAM

SITI SARAH AZMI


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Haemophilia A is inherited as an X-linked

recessive trait and thus occurs in males and in

homozygous females.

Most common genetic disorder associated with

serious bleeding due to reduction in theamount or activity of factor VII.

Hemophilia A is characterized by deficiency in

factor VIII clotting activity that results inprolonged oozing after injuries, tooth

extractions, or surgery, and delayed or

recurrent bleeding prior to complete wound

healing.


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SEVERITY FACTOR

VIII

CLOTTINGACTIVITY

SYMPTOMS USUAL AGE

OF

DIAGNOSED

Severe 5% - 35% No spontaneous bleeding;

abnormal bleeding aftermajor

injuries, surgery, or tooth

extractions .

Often later

in life.


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Haemophilia A is a recessive X-linked genetic

disorder involving a lack of functional clottingFactor VIII .

Factor VIII is an essential blood clotting factor

also known as anti-hemophilic factor (AHF).

In humans, Factor VIII is encoded by the F8

gene.

Defects in this gene results in hemophilia A, a

well known recessive X-linked coagulation

disorder.


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Factor VIII is the precursor to Factor VIIIa, which catalyzesthe activation of Factor IX to IXa.

Protein C and Protein S function to inactivate Factor VIIIa.

FVIII normally circulates in the plasma bound tovonWillebrand Factor. This association has several functionsincluding protecting FVIII from proteolysis, enhancing FVIIIsynthesis, and concentrating FVIII at the site of activehemostasis.

FVIII is a dimer with A,B,and C domains on each monomer.When activated, it becomes a trimer which has lost most ofthe B domain. (This is important concerning FVIIIinhibitors.)


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XX--LINKED RECESSIVE TRAITLINKED RECESSIVE TRAIT


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Females have two copies of the X chromosome, so if the factor VIII gene

on one chromosome doesn't work, the gene on the other chromosome can

do the job of making enough factor VIII.

Males, however, have only one X chromosome, so if the factor VIII gene on

that chromosome is broken, they will have hemophilia A. Thus, mostpeople with hemophilia A are male.

If a woman has a defective factor VIII gene, she is considered a carrier.

This means the defective gene can be passed down to her children.

There are four possible outcomes for the baby of a woman who is a

carrier. These four possibilities are repeated for each and every

pregnancy:

1. A girl who is not a carrier

2. A girl who is a carrier

3. A boy without hemophilia

4. A boy with hemophilia


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Hemophilia A is the most common severe bleeding disorder

Second most common congenital bleeding disorder ( after vWD)

Bleeding may occur anywhere.

The most common sites of bleeding are into joints (knees, ankles,elbows), into muscles, and from the gastrointestinal tract.

Spontaneous hemarthroses are so characteristic of severe hemophiliathat they are almost diagnostic of the disorder.

Patients with mild hemophilia bleed only in response to major trauma

or surgery.

Patients with moderately severe hemophilia bleed in response to mildtrauma or surgery, and those with severe hemophilia bleedspontaneously.


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The partial thromboplastin time (PTT) is prolonged

Pothrombin time, bleeding time, and fibrinogen

level, are normal.

Levels of factor VIII:C are reduced, butmeasurements of von Willebrand factor are normal

A low platelet count should raise a suspicion of HIV-associated immune thrombocytopenia. As HIV hasbecome relative common in the hemophiliacs due toprevious infected blood transfusions.


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The finding of a reduced factor VIII:C level will distinguishthis disorder from other causes of prolonged PTT

Clinically, factor VIII hemophilia is indistinguishable fromfactor IX hemophilia ( Hemophilia B)

In cases of mild hemophilia, the disorder needs to bedistinguished from von Willebrand's disease by VIII:A assay,

which shows normal levels of factor VIII antigen in theformer.

Female carriers can usually be identified by the presence oflow or normal levels of factor VIII:C with normal levels offactor VIII antigen


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Bleeding into joints, with associated pain andswelling.

Blood in the urine or stool

Bruising

Gastrointestinal tract and urinary tract hemorrhage.

Prolonged bleeding from cuts, tooth extraction, andsurgery

Spontaneous bleeding.


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Standard treatment : replacing the missing clotting factor

Mild hemophilia : desmopressin (DDAVP), which helps the bodyrelease factor VIII that is stored within the lining of blood vessels.

People with hemophilia and their families can be taught to give

factor VIII concentrates at home at the first signs of bleeding.

People with severe forms of the disease may need regular

preventative treatment.

Depending on the severity of the disease, DDAVP or factor VIII

concentrate may be given before having dental extractions and

surgery to prevent bleeding.

Immunization with hepatitis B vaccine.

Patients who develop an inhibitor to factor VIII may require

treatment with other clotting factors such as factor VIIa.


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Roberts HR. Hemophilia A and hemophilia B. In: Lichtman MA, et al., eds.

Williams Hematology. 7th ed. New York, NY: The McGraw-Hill Companies,

Inc.; 2006:chap 115.

Zhang B, Ginsburg D. Familial multiple coagulation factor deficiencies. In:

Colman RW et al (eds) Hemostasis and Thrombosis: Basic Principles and

Clinical Practice, 5 ed. Lippincott-Raven, Philadelphia, pp 953-9. 2006

Bagnall RD, Giannelli F, Green PM. Int22h-related inversions causing

hemophilia A: a novel insight into their origin and a new morediscriminant PCR test for their detection. J Thromb Haemost. 2006; 4: 591

8. [PubMed]

http://en.wikipedia.org/wiki/Haemophilia_A

[1] Kumar P, Clark M. Clinical Medicine. Fourth Ed. WB Saunders, 1998. pp

404 -406

Cheryl Brower, RN, MSPH.Clinical Nurse Specialist ,Puget Sound Blood

Center ,Seattle


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