What is von Willebrand disease (VWD)?

von Willebrand disease (VWD) is the most common type of bleeding disorder. People with VWD have a problem with a protein in their blood called von Willebrand factor (VWF) that helps control bleeding. When a blood vessel is injured and bleeding occurs, VWF helps cells in the blood, called platelets, mesh together and form a clot to stop the bleeding. People with VWD do not have enough VWF, or it does not work the way it should. It takes longer for blood to clot and for bleeding to stop.

VWD is generally less severe than other bleeding disorders. Many people with VWD may not know that they have the disorder because their bleeding symptoms are very mild. For most people with VWD, the disorder causes little or no disruption to their lives except when there is a serious injury or need for surgery. However, with all forms of VWD, there can be bleeding problems.

It is estimated that up to 1% of the world’s population suffers from VWD, but because many people have only very mild symptoms, only a small number of them know they have it. Research has shown that as many as 9 out of 10 people with VWD have not been diagnosed.

Types of VWD
There are three main types of VWD. Within each type, the disorder can be mild, moderate, or severe. Bleeding symptoms can be quite variable within each type depending in part on the VWF activity. It is important to know which type of VWD a person has, because treatment is different for each type.

Type 1 VWD is the most common form. People with Type 1 VWD have lower than normal levels of VWF. Symptoms are usually very mild. Still, it is possible for someone with Type 1 VWD to have serious bleeding.

Type 2 VWD involves a defect in the VWF structure. The VWF protein does not work properly, causing lower than normal VWF activity. There are different Type 2 VWD defects. Symptoms are usually moderate.

Type 3 VWD is usually the most serious form. People with Type 3 VWD have very little or no VWF. Symptoms are more severe. People with Type 3 VWD can have bleeding into muscles and joints, sometimes without injury.

source : http://www.wfh.org/en/page.aspx?pid=673

Meet Daniel

I see hemophilia as something that has inspired me to do more, to enjoy my wonderful family and to live as an active member of society.

— DANIEL KRAUS: Father. Rabbi. Hemophilia Advocate.

patient A severe 

"I have been asked many times what the negatives of living with hemophilia are. I find this question very presumptive. In fact, I see hemophilia as something that has inspired me to do more, to enjoy my wonderful family and to live as an active member of society.

"I have been involved with the hemophilia community over the years and was asked to join the board of a local chapter in New York in 2013. As someone with a bleeding disorder, I believe it is important for me to advocate for good care and the benefits of prophylactic treatment. I want to be an example for others with hemophilia. I think that it is very important for me to give back to the community that I have benefited from.

"I believe it's all about how you approach hemophilia and how you relate to it. I view hemophilia not as something that can inhibit me but as something that can benefit me. Sure, I have had painful bleeds, but I look at my hemophilia as a characteristic of mine, like being fat or thin, tall or short.

"I tell others with hemophilia to approach life with vigor and to be the best person that they can be. I tell them that they shouldn't see their hemophilia as a brick wall; after all, even though I have to take extra precautions when doing activities and traveling, I don't let my hemophilia stand in the way, and I don't let it define me.

"I found my True Identity by taking care of myself and being active in the hemophilia community."

Not all activities are appropriate for all people. Be sure to consult your physician or treatment center before beginning any exercise program or participating in sporting activities. If an injury occurs, contact your physician or treatment center immediately for the appropriate treatment.

You should be trained on how to do infusions by your hemophilia treatment center or your healthcare provider.

source : http://www.yourtrueid.com/real-stories/daniel.html

India hospital transfusions infect thousands with HIV

At least 2,234 Indians have contracted HIV while receiving blood transfusions in hospitals in the past 17 months alone, say officials.

The information was revealed by the country's National Aids Control Organisation (Naco) in response to a petition filed by information activist Chetan Kothari.

Mr Khothari told the BBC that he was "shocked" by the revelation.

India has more than two million people living with HIV/Aids.

The highest number of patients who had been infected with HIV as a result of contaminated blood in hospitals, were from the northern state of Uttar Pradesh with 361 cases, Mr Kothari's RTI (Right to Information) query revealed.

The western states of Gujarat with 292 cases and Maharashtra with 276 cases rank second and third respectively.

The Indian capital Delhi is at number four with 264 cases.

"This is the official data, provided by the government-run Naco. I believe the real numbers would be double or triple that," Mr Kothari told the BBC.

Under law, it is mandatory for hospitals to screen donors and the donated blood for HIV, hepatitis B and C, malaria and other infections.

"But each such test costs 1,200 rupees ($18; £12) and most hospitals in India do not have the testing facilities. Even in a big city like Mumbai, only three private hospitals have HIV testing facilities. Even the largest government hospitals do not have the technology to screen blood for HIV," Mr Kothari said.

"This is a very serious matter and must be addressed urgently," he added.

source : http://www.bbc.com/news/world-asia-india-36417789

Hemophilia doesn’t slow down district golf champ Ben Gruher

Union golfer needs as many as three injections a week to control condition

 

By Micah Rice, Columbian Sports Editor
Published: October 10, 2015, 10:55 PM

When Ben Gruher defends his 4A district golf title this week, he might face a high-pressure putt or a nasty lie in the rough.

Just don’t expect him to be rattled.

Since before he was 10, Gruher has had to inject himself at least three times a week with medicine to treat a severe form of hemophilia. At an age when kids are figuring out puzzles or action figures, he was learning to plunge a syringe into a vein in his arm.

Golf? That’s child’s play.

But through golf, the junior at Union High School has become an ambassador of sorts for other youths with hemophilia, a condition characterized by the blood’s inability to clot.

Every year, Gruher travels to Arizona for a golf and baseball event that gathers young hemophiliacs from around the nation. Hosted by pro golfer Perry Parker, Gruher was invited last year to speak as an alumnus of an event he first played at age 7.

“I feel that’s a really good way to get to know more hemophiliacs and give back to the community, because they’ve given me so much through that event,” Gruher said after a golf match last week.

By 10, Gruher had won two dozen youth tournaments and competed against kids from around the world. His story was featured by the National Hemophilia Foundation as an example of someone who isn’t limited by his condition.

Not much has changed in the seven years since. Yes, Gruher has sprouted to 6-foot-3 after growing seven inches in the past two years. But he’s still really good at golf. And he still doesn’t let hemophilia slow him down.

“Honestly, I never think about hemophilia,” Gruher said. “I’ve done infusions for so long that it’s just another poke. It’s a pain, but when I’m playing golf, hemophilia doesn’t come into my mind at all. I’m really thankful for that.”

A perfect sport

Ben’s parents, Jim and Monica Gruher, knew something wasn’t right when their first child was 8 months old. As baby Ben learned to crawl, large long-lasting bruises would appear.

Eventually, a blood test diagnosed Ben with a severe form of Hemophilia A, a hereditary condition that occurs in about 1 in 5,000 males, according to the National Hemophilia Foundation.

If hemophilia is left untreated, cuts can bleed until blood loss becomes a danger. But the more common concern is internal bleeding that can come from something like a sprained ankle or minor collision.
Gruher was prescribed medication that bolsters his blood’s ability to clot. He takes it intravenously at least three times a week and every other day during golf season.

Contact sports are typically off limits for hemophiliacs. Gruher stopped playing basketball in the fourth grade when the game became too physical. But he has always loved golf since he first picked up a plastic club as a 3 year old.

The game came naturally. At 5, he shot 50 for nine holes despite using just a 7-iron and a putter.
By 9, Gruher was regularly competing in and winning tournaments. He finished 13th out 150 kids in his age group at the U.S. Kids Golf World Championships in Pinehurst, N.C.

“He never gets too high or too low,” Jim Gruher said. “If he hits it out of bounds, he doesn’t like it, but he doesn’t freak out about it either.”

Hemophilia doesn’t affect Gruher on the course. But he sometimes gets bleeding within his muscles or joints that cause discomfort. When he extends his leg at the knee, a pop is heard from fluid left over from a bleeding episode in January.

He now plays the majority of his golf during the summers, including several events with the Oregon Junior Golf Association. But a highlight of his sophomore high school season was winning the 4A district title by one stroke over Brian Humphreys, a Camas senior who won the state title as a freshman and placed second as a sophomore.

Earlier this season, Gruher beat Humphreys in a playoff to win the Jeff Hudson Invitational at the same Tri-Mountain course that will host districts on Monday and Tuesday.

“Brian and I are probably going to be pretty close,” Gruher said of his friend. “I respect his game and he respects mine. We’ll see who comes out on top, but it’s going to be really fun.”

Union golf coach Gary Mills sees the effort Gruher devotes to golf.

“Some people are born to be great at a sport,” Mills said. “But in golf, you have to make yourself great. He’s very driven and very goal-oriented.”

And that drive means never letting hemophilia grab the wheel.

“He has never once complained about having hemophilia,” Jim Gruher said. “He never uses it as an excuse.”

source : http://www.columbian.com/news/2015/oct/10/hemophilia-doesnt-slow-down-district-golf-champ-ben-gruher/ 


 

Baby Boomers With Hemophilia Didn't Expect To Grow Old

Randy Curtis has hemophilia. These days he regularly injects the clotting factor treatments he needs from home, as a relatively easy way of preventing the episodes of catastrophic bleeding that plagued him as a child.

Lesley McClurg/KQED

Randy Curtis was in second grade when he and his parents got devastating news from a specialist in blood disorders. Curtis had merely fallen and bumped his knee, but he remembers the doctor's words: " 'You know, these kids don't really live past 13.' "

"So, I went back to school the next day," Curtis remembers, "and told my math teacher, 'I don't have to learn this stuff. I'm going to be dead!' "

He was wrong.

Curtis, now 61 years old, has hemophilia, a rare genetic disorder that makes his liver unable to produce a protein that helps blood clot. Only about 1 in 5,000 boys in the U.S., and significantly fewer girls, are born with the blood disorder. Today, Curtis is part of a cadre of men and women who faced and escaped death more than once because of twists and turns in the treatment of hemophilia — men and women now looking toward a retirement they never expected to see.

Like many kids born in the 1950s with the disorder, Curtis wore protective gear as he was growing up, to prevent injuries. He went to school in a wheelchair. He wore braces on his elbows and knees. He spent recess in the school office because even a hard bump or a fall could spark days of internal bleeding.

"For these children, the bleeding doesn't stop," explains Marion Koerper, a retired hematologist at the University of California, San Francisco. "After six or eight hours the ankle or the knee joint is swollen to the point where it's extremely painful. They can't straighten their leg, they can't walk on their leg and they need to be brought in for treatment."

In the 1950s scientists had discovered that donations of fresh frozen plasma, which contains clotting factors, could be transfused into patients in a hospital. But it took days to transfuse enough of the product to provide relief for a painful joint bleed, and many children died from bleeding inside the skull.

Sporting a shiner wasn't all that unusual for Curtis at age 2. The bleeding disorder he inherited prompted frequent bruising.

Courtesy of the Curtis family

Curtis' childhood was peppered with weeklong trips to the hospital for these transfusions. And he lived in fear of an intracranial bleed that would take his life. In 1960, the life expectancy for people with severe hemophilia was still less than 20 years.

Then, in the late 1960s, scientists discovered how to make freeze-dried concentrates of the clotting factors from blood. That transformed treatment; soon people with hemophilia could store the clotting factor they needed at home and infuse it on a regular basis, instead of waiting for emergency treatment in the hospital.

Curtis has given himself an intravenous injection of clotting factor every few days since he was 14 years old and says the home regimen gave him his life back. No more bleeds. No more hospitals. As long as Curtis injected his medicine his blood would clot normally.

"About my second year in college I realized that with the new products that they had out, I was going to have to get a job!" Curtis says. "It was a shocking revelation. And I had a plan for employment."

He graduated in 1977 with a degree in genetics. He went on to marry, have a son and enroll in an M.B.A. program.

"Then it all came crashing down when we discovered how many were infected with HIV," says Koerper.

She's referring to the medical disaster that occurred in the early 1980s as part of the wider tragedy of the AIDS epidemic. In those years, before HIV was identified, and before sensitive blood screening tests for the virus were developed, some of the clotting factor concentrate was derived from blood inadvertently contaminated with HIV (and, as doctors would later realize, also sometimes contaminated with the hepatitis C virus).

According to the National Hemophilia Foundation, "From the late 1970s to the mid-1980s, about half of all people with hemophilia became infected with HIV after using contaminated blood products. An estimated 90 percent of those with severe hemophilia were infected with HIV. Many developed AIDS and thousands died."

"Those were really dark days," Koerper says. "I looked at my patients and said, 'You're going to die.' " An estimated 10,000 people in the U.S. with hemophilia became infected with HIV.

"A lot of my really good friends are gone," says Curtis. "A lot of their wives are gone, because there was a lot of spread of HIV before we even knew it was HIV."

Curtis was one of the lucky ones; he never contracted HIV.

But a few years ago, he was treated for hepatitis C — an infection that he most likely picked up in the early 1980s, his doctors say.

Doctors put casts on Curtis during summer months when he was a child, to immobilize his ankles and prevent injuries.

Courtesy of the Curtis family

"This was 48 weeks of hell," Curtis says of the treatment. "This was interferon, ribavirin and all this stuff that gave you, basically, the flu everyday for 48 weeks."

The drugs successfully knocked out the hepatitis C virus, but treatment took a toll. Curtis' system is still recovering a year later from all the drugs.

Fortunately, viral contamination of clotting factors is no longer the threat that it used to be for people with hemophilia, because the majority of today's medication isdeveloped in a lab through the use of DNA technology, rather than sourced from human blood.

 Pharmaceutical companies manufacture hemophilia treatments at plants like BayerHealthCare's biotech plant in Berkeley, Calif. The company was one of the early players in helping to develop clotting factor as a treatment.

Now researchers are looking beyond treatment, toward the possibility of a cure — using some of the latest advances in genetics.

The company recently partnered with CRISPR Therapeutics — a gene-editing startup. Bayer is investing $300 million in the partnership in hopes of altering the genes involved in hemophilia.

"The hope could be that in about 10 years a gene therapy product could become available," says Hansjoerg Duerr, head of global strategic marketing with Bayer's hematology unit.

Meanwhile, Curtis is enjoying retirement. He is almost giddy when he looks back on his life.

"I've been really lucky," says Curtis. "I mean I'm vertical! Right? I can't complain."

Still, hemophilia treatment is extremely expensive. Curtis' annual treatment costs around $250,000. (The average costs, recent research shows, average around $300,000).

Insurance covers most of his costs, he says; he pays about $1,000 a year for the treatment.

When he hears legislators balking at the high cost of of treatment and suggesting that taxpayer-funded, emergency insurance programs should be cut, Curtis says he has a ready response: " 'It's going to cost you more if we show up in the ER.' "

Still, the high cost of treatment and a lack of access to the drugs leaves most people in developing countries who have hemophilia without good treatment, according to theWorld Federation of Hemophilia. The majority of patients globally who are born with the condition still don't see puberty.

Curtis plans to spend a lot of his retirement volunteering with the world federation and with the National Hemophilia Foundation as they work to improve international care.

"We're building tools for developing countries," Curtis says, "and showing them how to collect data and do their own advocacy."

This story was produced by KQED's health and technology blog,

source : http://www.npr.org/sections/health-shots/2016/06/20/481936195/baby-boomers-with-hemophilia-didnt-expect-to-grow-old

Questions & Answers

What is the difference between hemophilia A and hemophilia B?

The most common type of hemophilia is called hemophilia A. This means the person does not have enough clotting factor VIII (factor eight).
A less common type is hemophilia B. This person does not have enough clotting factor IX (factor nine).
The result is the same for people with hemophilia A and B: they both bleed for a longer time than normal.

Is hemophilia lifelong?

A person born with hemophilia will have it for life. The level of factor VIII or factor IX in the blood usually stays the same throughout the person’s life.

How common is hemophilia?

Hemophilia is quite rare. About 1 in 10,000 people is born with hemophilia A. About 1 in 50,000 people is born with hemophilia B.

Are there other types of bleeding disorders?

Yes, there are several other factor deficiencies that also cause abnormal bleeding. These include deficiencies in factors I, II, V, VII, X, XI, XIII and von Willebrand factor. The most severe forms of these deficiencies are even rarer than hemophilia A and B.
More information on von Willebrand disease, rare clotting factor deficiencies, and inherited platelet disorders.

How serious is hemophilia?

The severity of hemophilia depends on the amount of factor VIII or factor IX in the blood.
There are three levels of severity: mild, moderate, and severe. People with severe hemophilia usually bleed frequently into their muscles or joints. They may bleed one to two times per week. Bleeding is often spontaneous, which means it happens for no obvious reason.
People with moderate hemophilia bleed less often, usually after an injury. Cases of hemophilia vary, however, and a person with moderate hemophilia can bleed spontaneously.
People with mild hemophilia usually bleed only as a result of surgery or major injury.

What is acquired hemophilia?

In rare cases, a person can develop hemophilia later in life. The majority of cases involve middle-aged or elderly people, or young women who have recently given birth or are in the later stages of pregnancy.
Acquired hemophilia is usually caused by the development of antibodies to factor VIII or factor IX: the body’s immune system destroys its own naturally produced factor VIII.
This condition often resolves with appropriate treatment.

Does hemophilia only affect men?

The most severe forms of hemophilia affect almost only males. Women can be seriously affected only if the father has hemophilia and the mother is a carrier, which is extremely rare.
However, many women who are carriers have symptoms of mild hemophilia.

Are there any precautions a carrier of hemophilia should take if she becomes pregnant?

A carrier’s hematologist should be involved in the supervision of the pregnancy and should consult with the obstetrician before delivery. It is not necessary to perform prenatal diagnosis just for management of the pregnancy. This is only done if termination of pregnancy is being considered in the case of an affected child.

The factor VIII level (but not factor IX) tends to rise during pregnancy but should be checked sometime in the month or so before delivery.

A normal vaginal delivery is perfectly acceptable even if the fetus is male and at risk of hemophilia. Epidural anesthesia does not usually present a problem and is generally possible if the patient’s factor level is 40 percent or more. A cord blood sample after delivery will be used to check if a male baby has hemophilia. 

How is hemophilia diagnosed?

Hemophilia is diagnosed by taking a blood sample and measuring the level of factor activity in the blood. Hemophilia A is diagnosed by testing the level of factor VIII coagulation activity in the blood. Hemophilia B is diagnosed by measuring the level of factor IX activity.
If the mother is a carrier, testing can be done before a baby is born. Prenatal diagnosis can be done at 9 to 11 weeks by chorionic villus sampling (CVS) or by fetal blood sampling at a later stage (18 or more weeks).
These tests can be done at a hemophilia treatment centre. Consult the Global Treatment Centre Directory for information on treatment centres around the world. 

Where do bleeds occur?

Most bleeding in hemophilia occurs internally, into the joints or muscles.
The joints that are most often affected are the knee, ankle, and elbow. Repeated bleeding without prompt treatment can damage the cartilage and the bone in a joint, leading to chronic arthritis and disability.
The most serious muscle bleeds are the iliopsoas muscle (the front of the groin area), the forearm, and the calf.
Some bleeds can be life-threatening and require immediate treatment. These include bleeds in the head, throat, gut, or iliopsoas.

Are bruises dangerous?

Bruises are very common in children with hemophilia. A bruise is not usually cause for alarm, unless it is on the person’s head or neck, the person has a hard time moving, the bruise hurts, the lump in the bruise gets larger or does not go away, or if there is numbness or a tingling feeling along with the bruising. In any of these cases, a physician or local hemophilia treatment centre should be consulted.

Should people with hemophilia avoid aspirin and other similar non-steroidal anti-inflammatory drugs (NSAIDs)?

People with hemophilia should not take aspirin (ASA or acetylsalicyclic acid), or anything containing aspirin, as well as other NSAIDs, because they interfere with the stickiness of platelets and can make bleeding problems worse. Paracetamol (acetominophen) is a perfectly safe alternative to aspirin to relieve pain.
A list of medications that can interfere with bleeding.

Should people with hemophilia exercise and play sports?

Some people with hemophilia avoid exercise because they think it may cause bleeds, but exercise can actually help prevent them. Strong muscles help protect someone who has hemophilia from spontaneous bleeds and joint damage.
Sport is an important activity for young people. It helps build muscle and develop mental concentration and coordination. However, some sports are riskier than others, and the benefits must be weighed against the risks. The severity of a person’s hemophilia should also be considered when choosing a sport. Sports like swimming, badminton, cycling, and walking are safe for most people with hemophilia, while American football, rugby, and boxing are usually not recommended.

What are inhibitors?

Inhibitors are a serious medical problem that can occur when a person with hemophilia has an immune response to treatment with clotting factor concentrates.

Sometimes, a person's immune system reacts to proteins in factor concentrates as if they were harmful foreign substances because the body has never seen them before. When this happens, inhibitors (also called antibodies) form in the blood to fight against the foreign factor proteins. This stops the factor concentrates from being able to fix the bleeding problem.
Bleeding is very hard to control in someone with hemophilia who develops inhibitors.
More information on inhibitors.

What is prophylaxis?

Prophylaxis is the regular use of clotting factor concentrates to prevent bleeds before they start. Injections of clotting factor are given one, two or three times a week to maintain a constant level of factor VIII or IX in the bloodstream.
Prophylaxis can help reduce or prevent joint damage and improve the quality of life of people with hemophilia. In countries with access to adequate quantities of clotting factor concentrates, this is becoming the normal mode of treatment for younger patients, and can be started when the veins are well developed (usually between the ages of two and four years).

What is a venous access device (port-a-cath)?

A port-a-cath, or implantable venous access device (VAD), is a device that’s implanted under the skin, usually in the chest but sometimes in the arm. It has a reservoir connected to a catheter, which is then threaded into a vein. This way, medications and fluids can be injected easily, without having to ‘find a vein’ for each injection.
VADs have made prophylaxis (regular infusions of factor concentrates) in hemophilia much easier for families. However, there are risks. Some studies have shown an infection rate as high as 50%. These infections can usually be treated with intravenous antibiotics but sometimes the device must be removed. There is also a risk of clots forming at the tip of the catheter. Like for any other procedure, each family must weigh the risks and benefits.

Is there a cure for hemophilia?

There is no cure for hemophilia. Gene therapy remains an exciting possibility and holds out the prospect of a partial or complete cure. There are many technical obstacles to overcome, but research currently underway is encouraging.
Technically, a liver transplant can cure hemophilia, since coagulation factors are produced by cells inside the liver. However, the risks of surgery and the requirement for lifelong medication to prevent rejection of the transplanted organ may outweigh the benefits.

What is the life expectancy of someone with hemophilia?

The life expectancy of someone with hemophilia varies depending on whether they receive proper treatment. Without adequate treatment, many people with hemophilia die before they reach adulthood. However, with proper treatment, life expectancy for people with hemophilia is about 10 years less than that of males without hemophilia, and children can look forward to a normal life expectancy.



source : http://www.wfh.org/en/page.aspx?pid=637

Hemophilia ‘cures’ are proving gene therapy really is all it’s cracked up to be

• By Graham Templeton on June 15, 2016 at 12:30 pm

Gene therapy is part of an increasingly large collection of research fields: those with a huge, useless backlog of innovations. Gene therapy researchers have spent decadesdeveloping amazing, world-changing therapies with absolutely no ability to use those therapies outside of a test tube, or at best a cloned rodent. Now, with the advent of advanced gene-editing tech, we can apply them, and dozens of genetically inherited diseases could soon be curable as the result. The latest example is hemophilia, and the incredible recent progress toward a cure (or cures) show just how much potential the field really has.

Hemophilia is a disease defined by insufficient clotting of the blood, and in extreme cases it can lead to excessive bleeding with as little as a small bruise. One of the two main types of the disease is called hemophilia B, caused by a deficiency in a particular clotting protein, called Factor IX. Injections that can currently provide a synthetic version to replace factor IX can be ruinously expensive — one patient told Technology Review his treatments cost three quarters of a million dollars per year.

One of the main centers making progress in this field is called Spark Therapeutics, which recently announced findings in four human patients: the patients given gene therapy treatment showed naturally produced (“endogenous”) factor IX production to about 30% that of a healthy person. That’s far from what we would call a healthy level, but it does provide a huge proportion of the most important therapeutic effects of the injections — namely, it stops bleeding from truly incidental trauma like bruises and sprains.

A simplified schematic of the CRISPR system. RNA guides Cas9 in cutting at the CRISPR sequences.

Though the treatment is in no way a pass to a totally normal life — at least, not yet — it does allow patients to forego their injections without taking on any unreasonable risk during the basic activities of life. That’s the threshold of a cure; not a perfect cure, mind, but a cure nonetheless, and there’s every reason to believe the effectiveness could improve in the future.

It’s a breakthrough that has the potential to affect the lives of millions of men — men because, as a recessive, X chromosome-linked disease, hemophilia A and B are both found virtually entirely in the male population. Women, with their second X chromosome, have a second chance to get a healthy version of the gene and thus have a much smaller chance of getting the associated disease. About 1 in 5,000 males is born with Hemophilia A, which has to do with the function of the protein factor VIII, and 1 in 30,000 is born with hemophilia B, due to defective versions of factor IX.

In fact, the challenge at this point may be as much to modulate the effect down as up, with national regulators beginning to worry that increasing the natural factor IX output could lead to accidental over-compensation, and the production of potentially fatal blood clots. Just a few years ago, the whole idea of increasing this sort of protein output through gene therapy was considered at least a bit idealistic; today, there are genuine concerns about how to keep from increasing those protein levels too far.

An adeno-associated virus much like Spark’s custom-engineered one affecting these diseased liver cells.

One big reason is that gene therapy technologies for inserting genetic material into the cells of interest are still very primitive in an objective sense; only a minority actually reach their targets, and only a minority of these actually manage to get their genetic payload into the cells. As a result, these early therapies must usually find a way to augment the baseline infection rate of their therapeutic virus. Most commonly, they infect a small proportion of cells and allow those cells to out-compete non-infected ones, simply because they’re healthier. In this case, without such an evolutionary mechanism to help them, the scientists had to go for a more extreme version of the factor IX protein.

That’s why the worry about over-clotting: the version of factor IX that is being used by the therapy was in fact found and copied from a real patient suffering from overly common blood clots. Despite the low number of cells “fixed” through insertion of the super-factor IX, its incredible level of activity, almost eight times that of the natural version, allows it to make up for its low concentration. And the team has already increased the infection rate by making their custom virus head more directly for the liver, where its therapeutic genes are actually needed. Only time will tell whether it turns out to be safer and more effective to increase the virus’ infection rate for the target cell type, or the protein’s clotting strength, or both.

Unlike real viruses, these therapeutic ones have been neutered of their replication mechanisms, meaning that the low infection rate can’t become a high one without another deliberate infusion of the virus from doctors — so it’s not likely the protein levels will run away unexpectedly. Still, it’s worth being cautious with anything derived from a quasi-living entity evolved very specifically to do things to our cells that our cells want to stop them from doing. Putting such microscopic beasts to work is a very powerful approach, but it’s one that requires great care as well.

source : http://www.extremetech.com/extreme/230215-hemophilia-cures-are-proving-gene-therapy-really-is-all-its-cracked-up-to-be

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Study suggests another look at common treatments for hemophilia

Date:

June 13, 2016

Source:

Rush University Medical Center

Summary:

Participants who received a recombinant therapy— the present standard in the United States — developed antibodies or “inhibitors” to the treatments at almost twice the rate as those whose treatments were made from human plasma, new research shows.

Families of children with severe hemophilia A may want to take a fresh look at treatment options from human plasma. A study published in the New England Journal of Medicine on May 26 showed that participants who received a recombinant therapy -- the present standard in the United States -- developed antibodies or "inhibitors" to the treatments at almost twice the rate as those whose treatments were made from human plasma.

Recombinant Factor VIII, derived from a hamster cell line, was associated with an 87 percent higher likelihood that the patient would develop inhibitors, which can make the standard treatment ineffective, than the alternative, Factor VIII derived from human plasma with von Willebrand factor, a naturally occurring protein apparently protective of Factor VIII.

"Families will want to have a discussion with their physicians about how this study might impact the treatment options," said Dr. Mindy Simpson, a Rush University hematologist-oncologist who participated in the international study. The Hemophilia and Thrombophilia Center at Rush University Medical Center, the largest program of its kind in Illinois, was one of seven centers in the United States to take part in the study, Simpson said.

The study, the Survey of Inhibitors in Plasma-Products Exposed Toddlers, or SIPPET, is the first randomized, controlled study of the associations between inhibitors and the two first-line treatments for hemophilia A.

"Who is developing inhibitors, and why? This study is the first to try to sort out the answer to those questions regarding the factor treatment options," Simpson said.

Hemophilia is a rare genetic condition, affecting mostly boys, that hinders the production of an important clotting factor, Factor VIII in the more common hemophilia A, and Factor IX in hemophilia B. People with severe hemophilia can bleed excessively from even minor injuries. Untreated, hemophilia can be disabling and even fatal.

The best treatment for a "bleed" caused by hemophilia, or in some cases even to prevent bleeds from occurring is injection with the appropriate clotting factor, either drawn from human plasma, or a recombinant product.

Recombinant Factor VIII has been the preferred treatment for hemophilia A in part because patients died in large numbers after the human blood supply was tainted with HIV and hepatitis C in the 1980s, Simpson said.

"Patients and families have been afraid of plasma-derived products even though they have been safe for decades," Simpson said. There have been no transmitted cases of HIV or hepatitis C in hemophilia factor products since the 1990s.

The development of inhibitors, which occurs in about 30 percent of patients, is a major problem in the management of hemophilia A. When inhibitors appear in high titers -- that is, large numbers of antibodies per unit of blood -- the factor VIII replacement products are no longer effective to treat or prevent bleeding. That individual must then use more expensive and potentially less effective treatments. Patients who develop inhibitors usually do so early on, within the first 50 treatments.

SIPPET was conducted between 2010 and 2015, with 251 previously untreated young children in 42 centers in 14 countries, on five continents. The study, which does not have direct implications for patients with hemophilia B, was led by investigators Flora Peyvandi and Pier Mannuccio Mannucci, and sponsored by the Angelo Bianchi Bonomi Foundation, with funding from the Italian Ministry of Health and other groups.

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The above post is reprinted from materials provided by Rush University Medical Center. Note: Materials may be edited for content and length.

source : https://www.sciencedaily.com/releases/2016/06/160613111811.htm