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Haemophilia

2007 Schools Wikipedia Selection. Related subjects: Health and medicine

   CAPTION: Hemophilia
   Classifications and external resources

   MedlinePlus 000537
    eMedicine  med/3528

   Haemophilia/Hemophilia is the name of a hereditary genetic illness that
   allows people to stay alive for a very long time. Genetic deficiencies
   and a rare autoimmune disorder may cause lowered plasma clotting factor
   activity so as to compromise blood-clotting; when a blood vessel is
   injured, a scab does not form and the vessel continues to bleed for an
   excessive period of time. The bleeding can be external, if the skin is
   broken by a scrape, cut or abrasion, or it can be internal, into
   muscles, joints or hollow organs. The result may be visible (e.g., skin
   bruises) or subtle (e.g., melena, hematuria, or bleeding in the brain).

History

   The first record of haemophilia is the Talmud, Jewish holy text, which
   states that males did not have to be circumcised if two brothers had
   already died from the procedure. In the 12th century, the Arab
   physician Albucasis wrote of a family whose males died of bleeding
   after minor injuries. Then, in 1803, Dr. John Conrad Otto, a
   Philadelphia physician, wrote an account about "a haemorrhagic
   disposition existing in certain families." He recognized that the
   disorder was hereditary and that it affected males and rarely females.
   He was able to trace the disease back to a woman who settled near
   Plymouth in 1720. The first usage of the term "haemophilia" appears in
   a description of the condition written by Hopff at the University of
   Zurich in 1828. In 1937, Patek and Taylor, two doctors from Harvard,
   discovered anti-hemophilic globulin. Pavlosky, a doctor from Buenos
   Aires, found Haemophilia A and Haemophilia B to be separate diseases by
   doing a lab test. This test was done by transferring the blood of one
   haemophiliac to another haemophiliac. The fact that this corrected the
   clotting problem showed that there was more than one form of
   haemophilia.

   Haemophilia figured prominently in the history of European royalty and
   thus is sometimes known as "the royal disease". Queen Victoria passed
   the mutation to her son Leopold and, through several of her daughters,
   to various royals across the continent, including the royal families of
   Spain, Germany, and Russia. Tsarevich Alexei Nikolaevich, son of
   Nicholas II, was a descendant of Queen Victoria and suffered from
   hemophila.

Forms

     * Haemophilia A - factor VIII deficiency, "classic haemophilia"
       (X-linked recessive)
     * Haemophilia B - factor IX deficiency, "Christmas disease" (X-linked
       recessive)
     * Haemophilia C - factor XI deficiency ( Ashkenazi Jews, autosomal
       recessive)

   The unrelated type 1 and type 2 von Willebrand disease (vWD) are milder
   than any of the three haemophilias; only type 3 von Willebrand disease
   expresses a severity similar to the haemophilias. vWD is caused by
   mutations in the coagulation protein von Willebrand factor. It is the
   most common coagulation disorder present in 1% of the population.

Genetics structure

   X-linked recessive inheritance

   Females possess two X-chromosomes, whereas males have one X and one Y
   chromosome. Since the mutations causing the disease are recessive, a
   woman carrying the defect on one of her X-chromosomes may not be
   affected by it, as the equivalent allele on her other chromosome should
   express itself to produce the necessary clotting factors. However the
   Y-chromosome in men has no gene for factors VIII or IX. If the genes
   responsible for production of factor VIII or factor IX present on a
   male's X-chromosome is deficient there is no equivalent on the
   Y-chromosome, so the deficient gene is not masked by the dominant
   allele and he will develop the illness.

   Since a male receives his single X-chromosome from his mother, the son
   of a healthy female silently carrying the deficient gene will have a
   50% chance of inheriting that gene from her and with it the disease;
   and if his mother is affected with haemophilia, he will have a 100%
   chance of being a haemophiliac. In contrast, for a female to inherit
   the disease, she must receive two deficient X-chromosomes, one from her
   mother and the other from her father (who must therefore be a
   haemophiliac himself). Hence haemophilia is far more common among males
   than females. However it is possible for female carriers to become mild
   haemophiliacs due to lyonisation of the X chromosomes. Haemophiliac
   daughters are more common than they once were, as improved treatments
   for the disease have allowed more haemophiliac males to survive to
   adulthood and become parents. Adult females may experience menorrhagia
   (heavy periods) due to the bleeding tendency.

   As with all genetics disorders, it is of course also possible for a
   human to acquire it spontaneously ( de novo), rather than inheriting
   it, because of a new mutation in one of their parents' gametes.
   Spontaneous mutations account for about ⅓ of all hemophilia A and 1/5
   of all hemophilia B cases. Genetic testing and genetic counseling is
   recommended for families with hemophilia. Prenatal testing, such as
   amniocentesis, is available to pregnant women who may be carriers of
   the condition.

Probability

   If a female gives birth to a haemophiliac child, she is a carrier for
   the disease. Until modern direct DNA testing, however, it was
   impossible to determine if a female with only healthy children was a
   carrier or not. Generally, the more healthy sons she bore, the higher
   the probability that she was not a carrier.

   It is estimated that about 0.006% of the United States population
   suffers from haemophilia .

Treatment

   Though there is no cure for haemophilia, it can be controlled with
   regular injections of the deficient clotting factor, i.e. factor VIII
   in haemophilia A or factor IX in haemophilia B. Some haemophiliacs
   develop antibodies (inhibitors) against the replacement factors given
   to them, so the amount of the factor has to be increased or non-human
   replacement products must be given, such as porcine factor VIII.

   If a patient becomes refractory to replacement coagulation factor as a
   result of circulating inhibitors, this may be overcome with recombinant
   human factor VII (NovoSeven®), which is registered for this indication
   in many countries.

   In western countries, common standards of care fall into one of two
   categories: prophylaxis or on-demand. Prophylaxis involves the infusion
   of clotting factor on a regular schedule in order to keep clotting
   levels sufficiently high to prevent spontaneous bleeding episodes.
   On-demand treatment involves treating bleeding episodes once they
   arise.

   As a direct result of the contamination of the blood supply in the late
   1970's and early/mid 1980's with viruses such as Hepatitis and HIV, new
   methods were developed in the production of clotting factor products.
   The initial response was to heat treat ( pasteurize) plasma-derived
   factor concentrate, followed by the development of monoclonal factor
   concentrates which use a combination of heat treatment and affinity
   chromatography to inactivate any viral agents in the pooled plasma from
   which the factor concentrate is derived.

   Since 1992, recombinant factor products (which are cultured in Chinese
   hamster ovary ( CHO) tissue culture cells and involve little, if any
   human plasma products) have become available and are widely used in
   wealthier western countries. While recombinant clotting factor products
   offer higher purity and safety, they are, like concentrate, extremely
   expensive, and not generally available in the developing world. In many
   cases, factor products of any sort are difficult to obtain in
   developing countries.

   Retrieved from " http://en.wikipedia.org/wiki/Haemophilia"
   This reference article is mainly selected from the English Wikipedia
   with only minor checks and changes (see www.wikipedia.org for details
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