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Hemophilia
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Clinical types
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Hemophilia A - deficiency
of factor 8 in the hemostasis (blood clotting) mechanism.
Hemophilia B - deficiency
of factor 9 in the hemostasis mechanism
Other deficiencies in the hemostasis
system imitating hemophilia.
The different types of hemophilia can be differentiated by clinical and laboratory
findings after examination by a hematologist and/or geneticist.
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Clinical signs
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The severity of the condition depends on the degree of deficiency of the hemostasis
factor. In severely affected patients, the activity of the factor is less than 7%
of normal. Half of all hemophiliacs belong to this category. Due to the inability
to form blood clots there is a tendency for hemorrhages, mainly internal ones.
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These patients typically tend to bleed into joints after any slight trauma.
Sometimes hemorrhage occurs into other internal organs, the most ominous being into
the brain.
To correct this condition, the patients need repeated transfusions of the missing
factor.
Today, there is available a synthetically manufactured hemostasis factor, which
appears to be free of side effects.
This means that treatment today is effective, despite therapeutic discipline being
required.
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The diagnosis can be ascertained with accuracy using laboratory tests. The factor
that rectifies blood clotting is established - this is the missing factor in the
patient. In carrier women, the deficiency of the factor can be demonstrated in only
50% of cases. This means that a normal level of the factor does not rule out carrier
status in a woman who has an affected relative.
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Inheritance pattern
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X-linked.
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Penetrance
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In males, the disease is fully expressed.
Females carrying the gene can express a partial deficiency in the hemostasis factor
in specific situations where bleeding occurs, such as after birth or during an operation.
In such situations they also need a transfusion of the hemostasis factor they are
deficient in.
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Associated features that can be demonstrated by imagery
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Usually there are no defects that can be identified by ultrasound examination during pregnancy.
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What is the risk of recurrence in a subsequent pregnancy?
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It is necessary to consult a genetic counselor in order to determine the carrier
status of the mother based on the family pedigree.
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If there is only one patient in the family
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The mother need not necessarily be a carrier. If the couple has only one child with
hemophilia A or B, and he is the only known affected individual in the family, there
is a 66% chance that his mother is a carrier. Therefore in each subsequent pregnancy
with a male fetus, the couple has a 33% chance of having another affected son. In
these cases, the risk that a sister or maternal aunt of the patient will be a carrier
is half that of the mother.
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In cases where there are many affected individuals in the family
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Women who have given birth to more than one affected son are considered to be carriers,
with a 50% risk in every subsequent pregnancy that a male fetus will be affected
and a female fetus will be a carrier.
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Molecular genetic information
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The genes for the disease
Hemophilia A: F8C
Hemophilia B: F9C
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Genetic testing
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Diagnostic testing (identification of the genetic mutation and confirmation of the
disease)
Regarding diagnosis by non-genetic methods, see above under laboratory tests. Regarding
direct genetic testing to identify the mutation in the gene: the gene for hemophilia
is long and can be examined, but this test is not necessary for an exact diagnosis
of patients and is therefore not routinely performed. See: Screening test for identifying defects
(mutations) using various methods such as SSCP - X-linked diseases.
Carrier testing
50% of carriers have a reduced blood factor level (see above under laboratory tests).
Genetic carrier tests are divided in accordance with the family type:
In cases where there are many affected
individuals in the family, the defect (mutation) must be identified in
the patients. Testing for carriers in the family starts with the first-rank relatives
of the affected individuals, and initially, the daughters, sisters and mothers of
the patients are examined. Based on the results, the carrier tests can then be extended
to other women who are related to the patients and to the carriers detected in the
first round of tests. Each carrier identified can be offered prenatal diagnosis
in pregnancy - during this the sex of the fetus will be determined, and in the case
of a male fetus, whether or not he is affected. All these tests must be carried
out through a genetic institute - see Screening test for identifying defects
(mutations) using various methods such as SSCP - X-linked diseases.
If the mutation cannot be identified easily, an indirect test (linkage analysis)
can be performed, but not before it is established with certainty that the mother,
and any other woman in the family wishing to test her status, is a carrier. This
is based on analysis of the pedigree and must be discussed with the geneticist.
Hemostatic testing (see above) can also be carried out. Only then is it possible
to use the indirect tests for prenatal diagnosis. See: testing for genetic
markers in a family that has one or more patients - when there is only one gene
that can cause the disease - X-linked diseases.
In cases where the affected individual
is the only one in the family, his mother is not necessarily a carrier,
and other women in the family are certainly not obligate carriers. The mutation
must first be identified in the patient and looked for in his mother. If it is not
found in the mother, then this is a new mutation that has occurred in the patient.
Only his daughters (all his daughters) must be carriers, and they and their offspring
can be offered testing for the disease and for carrier status.
If the defect (mutation) found in the patient is also present in his mother, then
she is a carrier. Testing for carriers in the family starts with the first-rank
relatives of the affected individual, and initially, the daughters, sisters and
mothers of the patient are examined. Based on the results, the carrier tests can
then be extended to other women who are related to the carriers detected in the
first round of tests. Each carrier identified can be offered prenatal diagnosis
in pregnancy - during this the sex of the fetus will be determined, and in the case
of a male fetus, whether or not he is affected. All these tests must be carried
out through a genetic institute.
If the mutation cannot be identified easily, an indirect test (linkage analysis)
can be performed, but not before it is established with certainty that the mother,
and any other woman in the family wishing to test her status, is a carrier. This
is based on analysis of the pedigree and must be discussed with the geneticist.
Hemostatic testing (see above) can also be carried out. Only then is it possible
to use the indirect tests for prenatal diagnosis. See: testing for genetic markers in a family that has one or more patients - when
there is only one gene that can cause the disease - X-linked diseases.
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Fetal testing
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After it has been established that the woman (mother, sister, or a more distant
relative of a patient) is a carrier, genetic tests can be used for prenatal testing.
In the case of a male, it is possible to determine whether he has received the mutation
identified in the patients in the family. See: Screening test for identifying defects
(mutations) using various methods such as SSCP - X-linked diseases.
If the defect is not identified, indirect tests may be employed, once again on basis
that the mother is a carrier, because if she is not, the next fetus may be healthy
even if he has received the same allele as the affected child, because the affected
child may have a new mutation which occurred only in the ovum that created him -
see: testing for genetic markers in a family that has one or more patients - when
there is only one gene that can cause the disease - X-linked diseases.
The level of the hemostatic factor can also be measured in the fetus-s blood. These
tests were common in the past, but nowadays genetic tests usually give a reliable
diagnosis in all families, and are replacing the necessity for testing the fetus-s
blood.
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Hemophilia Health Byte
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