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Hemophilia A

Haemophilia A (also spelt Hemophilia A or Hæmophilia A) is a blood clotting disorder caused by a mutation of the factor VIII gene, leading to a deficiency in Factor VIII. It is the most common hemophilia. Inheritance is X-linked; hence, males are affected while females are carriers or very rarely display a mild phenotype. 1 in 10,000 males are affected. more...

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Signs and symptoms

Hemophilia leads to a severely increased risk of bleeding from common injuries. The sites of bleeding are:

  • joints
  • muscles
  • digestive tract
  • brain

The muscle and joint haemorrhages are quite typical of haemophilia, while digestive tract and cerebral haemorrhages are also germane to other coagulation disorders.

Diagnosis

The diagnosis may be suspected as coagulation testing reveals an increased PTT in the context of a normal PT and bleeding time. The diagnosis is made in the presence of very low (<10 IU) levels of factor VIII. A family history is frequently present, although not essential. Nowadays, genetic testing may also be performed.

The most important differential diagnosis is that of hemophilia B (also known as Christmas disease) or von Willebrand disease. The former is usually considered if factor VIII levels are normal in a person with a haemophilia phenotype. The latter is excluded on routine testing for that condition.

A very small minority of patients has antibodies against factor VIII that impair its functioning. Management of these patients is more complicated (see below).

Therapy

Most haemophilia patients require regular supplementation with intravenous recombinant factor VIII. This is highly individually determined. Apart from "routine" supplementation, extra factor concentrate is given around surgical procedures and after trauma. In children, an easily accessible intravenous port (e.g. Port-a-Cath) may have to be inserted to minimise frequent traumatic intravenous cannulation.

Some may manage on desmopressin, if the clotting factor is still partially active.

A particular therapeutic conundrum is the development of "inhibitor" antibodies against factor VIII due to frequent infusions. These probably develop as the body recognises the factor VIII as foreign, as the body does not have its own "copy". The problem is that in these patients, factor VIII infusions are ineffective. Recently activated factor VII (NovoSeven®) has become available as a treatment for haemorrhage in patients with haemophilia and factor inhibitors.

Read more at Wikipedia.org


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To stanch the flow: hemophilia drug curbs brain hemorrhage
From Science News, 2/26/05 by N. Seppa

There's no effective emergency treatment for a cerebral hemorrhage. Roughly 60 percent of people who experience this so-called bleeding stroke die within a year.

A new international study, however, indicates that a drug that speeds blood clotting can reduce death and disability after a bleeding stroke, provided that the person is treated promptly. The drug limits the amount of brain tissue damaged by blood leakage, a predictor of how damaging the stroke will be.

A cerebral hemorrhage kills neurons and other brain cells at the site of the bleeding and threatens cells on the hemorrhage's periphery. If a doctor could limit the bleeding, a patient would have a better chance of recovery, says study coauthor Stephan A. Mayer, a neurologist at the Columbia University College of Physicians and Surgeons in New York.

Mayer and a team of physicians in North America, Europe, Asia, and Australia treated 303 bleeding-stroke patients with an intravenous drug called recombinant activated factor VII (rFVIIa), which certain hemophilia patients receive under the brand name NovoSeven. The researchers gave a placebo infusion to 96 other patients with bleeding strokes. Upon admission to a hospital and 24 hours later, each participant underwent computed tomography brain scans to detect bleeding.

Patients receiving the drug had about half as much bleeding in the brain the day after admission as did those getting the placebo. Those receiving the largest of the three doses given in the study had the least bleeding, the researchers report in the Feb. 24 New England Journal of Medicine.

After 3 months, 69 percent of the people getting the placebo had died or were severely disabled, compared with 53 percent of those getting the drug.

"This is really an outstanding finding," says neurologist Lewis B. Morganstern of the University of Michigan Medical School in Ann Arbor. "This drug holds great promise as a targeted therapy for cerebral hemorrhage."

The drug had one serious side effect. It caused unwanted blood clots in some patients' brains and heart arteries. This safety concern led the researchers, midway through the trial, to stop accepting people who had a history of clotting problems, such as a previous heart attack, chest pains, or blocked leg veins.

The success of stroke treatment depends on getting the patient to a hospital quickly, Morganstern says. The study participants all received rFVIIa within 4 hours of their strokes. After that time, natural clotting has already ended most bleeding, and the risks of giving a clotting agent outweigh the benefits, Mayer says.

Some physicians have proposed that surgical drainage of cerebral hemorrhages could reduce damage from bleeding strokes. But an international group of researchers reported in the Jan. 29 Lancet that bleeding-stroke patients randomly assigned to undergo drainage surgery fared no better than did similar patients who didn't undergo that procedure.

COPYRIGHT 2005 Science Service, Inc.
COPYRIGHT 2005 Gale Group

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