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A disorder in which blood doesn’t clot normally.  When blood can’t clot properly, excessive bleeding occurs after injury or damage.  There are different types of hemophilia : A and B.

Hemophilia A:

1. Most common type

2. Person doesn’t have enough clotting factor 8

Hemophilia B:

1. Less common compared to hemophilia A

2. Caused by lack of blood clotting factor 9

3. Without clotting factor 9, the blood can’t clot properly to control bleeding

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Mutation in genes for factor VIII ( Hemophilia type A)

Deficiency in blood clotting factor

Mutation in genes for factor IX ( Hemophilia type B)

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Replacement Therapy

No cure

Gene Therapy

Medication

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Excessive bleeding from anywhere in the body

Long-term damage to joints

Repeated bleeding episodes

Blood in stool / urine

Swollen joints

Internal bleeding

Frequent nosebleeds

Prolonged Menstrual Cycles

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The delivery virus, carrying a good version of the human gene for the clotting agent known as Factor IX, was prepared by researchers at St. Jude Children's Research Hospital in Memphis. The patients had been recruited and treated with the virus in England by a team led by Dr. Amit C. Nathwani of University College London; researchers at the Children's Hospital of Philadelphia monitored their immune reactions.

Hemophilia B is caused by a defect in the gene for Factor IX. Fatal if untreated, the disease occurs almost only in men because the Factor IX gene lies on the X chromosome, of which men have only a single copy.

Women who carry a defective gene on one X chromosome can compensate with the good copy on their other X chromosome, but they bequeath the defective copy to half their children. About one in 30,000 of newborn boys have the disease, with about 3,000 patients in the United States.

Dr. Nathwani and his team reported that they treated the patients by infusing the delivery virus into their veins. The virus homes in on the cells of the liver, and the gene it carries then churns out correct copies of Factor IX. A single injection enabled the patients to produce small amounts of Factor IX, enough that four of the six could stop the usual treatment, injections of Factor IX concentrate prepared from donated blood. The other two patients continued to need concentrate, but less frequently.

Treating a patient with concentrate costs $300,000 a year, with a possible lifetime cost of $20 million, but the single required injection of the new delivery virus costs just $30,000, Dr. Katherine P. Ponder of the Washington University School of Medicine in St. Louis notes in her commentary in The New England Journal of Medicine, calling the trial "a landmark study."

The patients have continued to produce their own Factor IX for up to 22 months, said Dr. Edward G. D. Tuddenham, director of the Hemophilia Center at the Royal Free Hospital in London. One patient, a geologist, had a good response at first, but his level of Factor IX has declined to 1 percent of normal, the level at which the disease kicks in.

"We attribute this to the fact that he had an inflammation, and although we treated it promptly, we should have been quicker off the mark," Dr. Tuddenham said.

The patient cannot be injected again with the same virus because his immune system is now primed to attack it. "He's very philosophic about it, but he's a scientist, and his motivation is to help the science," Dr. Tuddenham said.

Twenty more patients will be treated to assess the best dose of the virus, the goal being the highest dose that does not set off an immune system attack, Dr. Tuddenham said. "We are pretty close to the sweet spot," he said. If all goes well, a genetic treatment for hemophilia B "could be available for widespread use in a couple of years."

In a trial in 2006, a patient injected with a corrective gene produced his own Factor IX but only for 10 weeks. The designer of that treatment, Dr. Katherine A. High of Children's Hospital of Philadelphia, said the new therapy had worked because the delivery virus had been made more efficient and because the research team had treated the patients with steroids to suppress immune system attacks on the virus.

"I think it's incredibly exciting, and I say that even though these people are my competitors," she said. Dr. High is listed as a co-author of the report because her laboratory helped monitor the patients and provided proof for regulators that the virus would not insert its human gene into the patients' sperm and make the change hereditary.

A serious problem with other delivery viruses is that they insert themselves randomly into chromosomes, sometimes disrupting a gene. The virus used by Dr. Nathwani's team, known as adeno-associated virus-8, generally stays outside the chromosomes, so it should not present this problem. Still, patients will need to be monitored for liver cancer, a small possibility that has been observed in mice.

"I don't think it's a showstopper, but it's a critical safety issue that has to be assessed," Dr. High said.

Patients have little or no immunity to the adeno-associated virus, which infects rhesus monkeys. The virus has a propensity for making liver cells its target, which is good for the therapy because these cells are the natural producers of Factor IX. However, liver cells do not live forever and slowly replenish themselves, possibly limiting how long the therapy will last.

About 80 percent of hemophilia cases are of the type known as hemophilia A, which is caused by defects in a different blood-clotting agent, Factor VIII. Researchers have focused on hemophilia B, in part, because the Factor IX gene is much smaller and easier to work with.

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The delivery virus, carrying a good version of the human gene for the clotting agent known as Factor IX, was prepared by researchers at St. Jude Children's Research Hospital in Memphis. The patients had been recruited and treated with the virus in England by a team led by Dr. Amit C.

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Therapies and healthcare delivery for men and boys with hemophilia have improved over the last five decades. Yet people affected by hemophilia still experience significant health challenges. In order to better address these challenges, it will be important to monitor and learn more about the health of people with hemophilia. This knowledge can be used to develop programs to help decrease illness and death from this disorder.
About the Study

Researchers from the Centers for Disease Control and Prevention (CDC) and the U.S. Hemophilia Treatment Center Network analyzed data from a health monitoring system that tracked care and health outcomes of boys and men with hemophilia in the United States. The study aimed to examine

Trends over time in the use of regular treatment to prevent bleeding episodes, called prophylaxis;

Changes over the same period in the health of each person's joints (such as the average number of bleeding episodes into a person's joints and the ability of the joints to move properly); and

The effect of beginning prophylaxis at various ages on the health of a person's joints over time for those between 2 and 19 years of age.

Researchers studied information collected from 6,196 males between 2 and 69 years of age with severe hemophilia A. These males received care at U.S. hemophilia treatment centers from 1999-2010. The data collected from all of their clinic visits were used to examine trends in prophylaxis use and changes in their health over the study period. In a separate study, data collected during the same period from 2,908 boys and young men were used to determine the age at which beginning prophylaxis worked best to preserve the ability of their joints to move properly.

We invite you to read the scientific summary of the study.

Main Findings from the Study

The use of prophylaxis by hemophilia patients to prevent bleeding increased from about one-third of patients in 1999 to half of all patients by the end of the study period.

Prophylaxis use was greater among patients younger than 20 years old with 3 in every 4 of these patients using this treatment to prevent bleeding by 2010.

Bleeding episodes in joints as well as in other places in the body decreased during 1999-2010, and in most cases the decrease was greater for those patients using prophylaxis.

Among patients under age 20, prophylaxis resulted in less bleeding at any age. However, only those who started prophylaxis before age 4 or those who were not obese, meaning they did not have excess body fat, retained the ability to move their joints normally.

Public Health Message

Starting young children with severe hemophilia on prophylaxis before age 4 years is the most effective way to preserve healthy joint function over the lifespan.

Critical Gaps in Information & Future Work
Gaps in Information
A number of observations from this study need further investigation to determine why they occur:

Prophylaxis through the regular infusion or injection of clotting factor concentrates into a vein to prevent bleeding was shown to result in better joint health. However, this study found that not everyone with hemophilia used prophylaxis.

It is not known why prophylaxis is best able to protect the ability of joints to move properly only when treatment is started at a very young age.

It is not known why all people with hemophilia don't use prophylaxis, and what might be the barriers that keep them from using this treatment.

Future Work
Studies are needed to understand why some boys and men with hemophilia do not use prophylaxis and to develop strategies that are successful in changing this behavior. More work is needed to understand the factors that may lead to joint bleeds and develop treatment strategies for men with hemophilia who have a higher risk for joint disease.

More Information

Please visit the following links for more information:

Hemophilia
https://www.cdc.gov/ncbddd/hemophilia/index.html

Treatment
https://www.cdc.gov/ncbddd/hemophilia/treatment.html

Public health monitoring programs for hemophilia and other bleeding disorders
https://www.cdc.gov/ncbddd/hemophilia/communitycounts/index.html

Key Findings Reference

Manco-Johnson MJ, Soucie JM, Gill JC. Prophylaxis usage, bleeding rate and joint outcomes of hemophilia 1999 - 2010: a surveillance project. Blood. 2017 Feb 9. pii: blood-2016-02-683169. doi: 10.1182/blood-2016-02-683169. [Epub ahead of print]

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Key Findings: New Study Shows That Regular Treatment for Hemophilia Starting Early in Life Can Prevent Joint Disease

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Therapies and healthcare delivery for men and boys with hemophilia have improved over the last five decades. Yet people affected by hemophilia still experience significant health challenges. In order to better address these challenges, it will be important to monitor and learn more about the health of people with hemophilia.