Women also Bleed

Women can have bleeding disorders, too. A bleeding disorder results from a flaw in the body’s clotting system. Specialized proteins in the blood are called clotting factors. If they are missing or do not work properly, a bleeding disorder can result. Most bleeding disorders are inherited, caused by a genetic mutation, but some can occur spontaneously. People with bleeding disorders bleed longer, not faster, than those who do not.

You may have a bleeding disorder if you have one or more of the following symptoms:

• I have heavy menstrual periods
• Bleeding for more than 7 days, from the time it began until it stopped
• Flooding or gushing of blood, limiting daily activities such as housework, exercise or social activities
• Passing clots that are bigger than a quarter
• Changing tampon and/or pad every 2 hours or less on heaviest day I have been told I am “low in iron” or I was treated for anemia

• I have bleeding symptoms and someone in my family has a bleeding disorder, such as von Willebrand disease, or a clotting factor deficiency, such as hemophilia

• I have experienced heavy bleeding from dental surgery, other surgery, or childbirth and/or have other additional bleeding symptoms such as:
• frequent prolonged nose bleeds (longer than 10 minutes) or
• prolonged bleeding from cuts (longer than 5 minutes) or
• easy bruising (weekly, raised and larger than a quarter)

If you have one or more of these symptoms, please speak with your doctor or other healthcare professional.

The most common bleeding disorder in women and girls is von Willebrand disease (VWD). It affects up to 1% of the U.S. population. VWD is an inherited bleeding disorder. It is caused by a defect in or deficiency of von Willebrand factor, a protein the blood needs for clotting.

Women and girls may also have mild hemophilia (“symptomatic carriers”), meaning that in addition to carrying the gene, they also exhibit symptoms. In some cases, females are diagnosed with hemophilia A, or factor VIII deficiency, or hemophilia B, factor IX deficiency—both of which are hereditary. Further, they can have any of the rare factor disorders, such as factor I, II, VI, VII, XI and XIII deficiency.

Although men and women with bleeding disorders have similar symptoms, such as bleeds into joints and tissues, women can experience added complications during menstruation, pregnancy, labor and delivery. Some doctors are not familiar with bleeding disorders in women, many of whom are undiagnosed or misdiagnosed. Women with undiagnosed and untreated bleeding disorders risk serious complications.

Victory for Women (V4W) is NHF’s health initiative to address the critical issues faced by women with bleeding disorders. V4W follows in the footsteps of “Project Red Flag: Real Talk about Women’s Bleeding Disorders”, which brought significant attention to the many women struggling for an accurate diagnosis and appropriate health care. Now that the flag has been raised, V4W continues the work, seeking to educate all about girls, women and bleeding disorders.

If you have symptoms of a bleeding disorder, it is important to get a proper diagnosis and treatment from a specialist, called a hematologist. In the U.S., there is a network of hemophilia treatment centers (HTCs) that provide comprehensive care to patients with hemophilia and other bleeding disorders. HANDI, the National Hemophilia Foundation’s information resource center, can provide information on bleeding disorders and the nearest HTC.

source : https://www.hemophilia.org/Community-Resources/Women-with-Bleeding-Disorders/Women-also-Bleed

Inhibitors

People with hemophilia have a higher quality of life today than ever before, but complications can still occur. Approximately 15-20% of people with hemophilia will develop an  antibody—called an inhibitor—to the product used to treat or prevent bleeding episodes. Developing an inhibitor is one of the most serious and costly complications of hemophilia.

About Inhibitors

People with hemophilia use treatment products called clotting factor concentrates. This treatment improves blood clotting and is used to stop or prevent a bleeding episode. Inhibitors develop when the body’s immune system stops accepting the factor (factor VIII for hemophilia A and factor IX for hemophilia B) as a normal part of blood. The body thinks the factor is a foreign substance and tries to destroy it using inhibitors. The inhibitors stop the factor from working. This makes it more difficult to stop a bleeding episode. People with hemophilia who develop an inhibitor do not respond as well to treatment. Inhibitors most often appear during the first year of treatment but they can appear at any time.

Cost of Care

Caring for people with inhibitors poses a special challenge. The health care costs associated with inhibitors can be staggering because of the cost and amount of treatment product required to stop bleeding. Also, people with hemophilia who develop an inhibitor are twice as likely to be hospitalized for a bleeding complication.

Risk Factors and Causes

Scientists do not know exactly what causes inhibitors. Risk factors that have been shown in some studies to possibly play a role include:

·         Age

·         Race/ethnicity

·         Type of hemophilia gene defect

·         Frequency and amount of treatment (inhibitors typically occur within the first 50 times factor is used)

·         Family history of inhibitors

·         Type of factor treatment product

·         Presence of other immune disorders

Diagnosis

A blood test is used to diagnose inhibitors. The blood test measures inhibitor levels (called inhibitor titers) in the blood. The amount of inhibitor titers is measured in Bethesda units (BU). The higher the number of Bethesda units, the more inhibitor is present. “Low titer” inhibitor has a very low measurement, usually less than 5 BU. “High titer” inhibitor has a very high measurement, usually much higher than 5 BU.

Inhibitors are also labeled “low responding” or “high responding” based on how strongly a person’s immune system reacts or responds to repeated exposure to factor concentrate. When people with high-responding inhibitors receive factor concentrates, the inhibitor titer measurement increases quickly. The increased inhibitor titer prevents the clotting factor concentrates from stopping or preventing a bleeding episode. Repeated exposure to clotting factor concentrates will cause more inhibitors to develop.

When people with low-responding inhibitors receive factor concentrates, the inhibitor titers do not rise. Therefore, people with low-responding inhibitors can usually still use clotting factor concentrates to stop or prevent a bleeding episode.
 

Treatment

Treating people who have inhibitors is complex and remains one of the biggest challenges in hemophilia care today. If possible, a person with inhibitors should be cared for at a hemophilia treatment center (HTC). HTCs are specialized health care centers that bring together a team of doctors, nurses, and other health professionals experienced in treating people with hemophilia.

Some treatments for people with inhibitors include the following:

·         High-Dose Clotting Factor Concentrates: People who have low responding inhibitors may be treated with higher amounts of factor concentrate to overcome the inhibitor and yet have enough left over to form a clot. It is important to test the blood and measure the factor level after this new treatment schedule is established to see if the inhibitor is gone.

·         Bypassing Agents: Special blood products are used to treat bleeding in people with high titer inhibitors. They are called bypassing agents. Instead of replacing the missing factor, they go around (or bypass) the factors that are blocked by the inhibitor to help the body form a normal clot. People taking bypassing agents should be monitored closely to make sure the blood is not clotting too much or clotting in the wrong place in the body.

·         Immune Tolerance Induction (ITI) Therapy: The goal of ITI therapy is to stop the inhibitor reaction from happening in the blood and to teach the body to accept clotting factor concentrate treatments. With ITI therapy, people receive large amounts of clotting factor concentrates every day for many weeks or months.

ITI therapy requires specialized medical expertise, is costly, and may take a long time to work. In many cases, ITI gets rid of the inhibitor. However, patients may need to continue taking frequent, large amounts of factor concentrates for many years to keep the inhibitor from coming back. HTCs can serve a vital role in supporting patients who undergo a treatment regimen as intensive as ITI.

CDC Research

CDC is interested in learning more about why some people develop inhibitors and how they could be prevented. The Inhibitor Project began in 2005 and was implemented to explore the following questions:

·         Does a change in treatment products (from one type of factor product to another) lead to an inhibitor?

·         Are people with specific gene mutations more likely to develop an inhibitor?

·         What characteristics make some people more likely to develop an inhibitor than others?

·         Why do some people develop inhibitors and others do not?

·         How often do inhibitors occur?

In the Inhibitor Project, a limited number of federally funded hemophilia treatment centers across the United States enroll study participants who have hemophilia A or hemophilia B. Detailed information about their hemophilia, their complications, and their treatment is collected and studied over time. The CDC laboratory tests each participant’s blood and determines if he or she has an inhibitor. Testing all of the blood at the CDC laboratory, rather than using several different labs throughout the country, ensures that the testing procedures are consistent and reliable for analysis. The blood samples are also used to study hemophilia-related genes and gene mutations to learn more about who is more likely to develop an inhibitor even before treatment is started. The laboratory results are shared with the study participant’s physician.

Through additional research, we hope to increase our understanding of inhibitors. Knowing more about why some people develop inhibitors and others do not may help us predict who will develop an inhibitor before treatment is started. This may lead to a decreased rate of inhibitors, decreased health care costs, and the licensure of safe and more effective treatment products for people with hemophilia.

Did You Know?

When people are being treated for an inhibitor, they receive frequent, large amounts of clotting factor concentrates and therefore may need a central venous access device (CVAD). A CVAD is a small tube placed in a vein. It can stay in the vein for a long time. Clotting factor concentrates can be given through the CVAD instead of by injection or infusion through a painful needle stick. A downside of having a CVAD is that people with CVADs are more likely to develop infections, blood clots, and other complications than those without CVADs. It is important for people with hemophilia and their caregivers to learn how to care for the device.

Source : http://www.cdc.gov/ncbddd/hemophilia/inhibitors.html

Hemophilia facts

• Hemophilia is one of a group of inherited bleeding disorders that cause abnormal or exaggerated bleeding and poor blood clotting.

• Hemophilia A and B are inherited in an X-linked recessive genetic pattern, so males are commonly affected while females are usually carriers of the disease.

• Hemophilia A is caused by a deficiency of clotting Factor VIII, while hemophilia B (also called Christmas disease) results from a deficiency of Factor IX.

• Hemophilia varies in its severity among affected individuals.

• Symptoms include excessive bleeding from any site in the body; long-term damage to joints from repeated bleeding episodes is characteristic.

• Treatment involves coagulation factor replacement therapy.

• The formation of inhibitors to the treatment factor concentrates is a significant complication of treatment.

• Gene therapy treatments are a source of active research and hold promise for the future.

source : http://www.medicinenet.com/hemophilia/article.htm

No hemophilia centre for 120m population of Punjab

LAHORE

Medical experts have observed that none of safe blood transfusion centres established eight years ago has been made functional while there is not a single hemophilia centre for the 120million population of Punjab.

“There are 17,000 to 18,000 hemophilia patients in Pakistan but 90 per cent of them do not get the required treatment,” they observed while speaking at a seminar on “Treatment for All is the Vision of All” organised in connection with World Hemophilia Day 2016, by the Mir Khalil-ur-Rahman Memorial Society (Jang Group of Newspapers) in collaboration with the Pakistan Society of Hematology (PSH) and novo nordisk here at a local hotel on Saturday.

Adviser to Chief Minister on Health Khawaja Salman Rafique said that hemophilia is a genetic disease transmitted among generations, saying that pain and misery inflicted by the diseases and its treatment can only by known by the patient and the family. He said the Punjab government had increased the health budget from Rs 25 billion to Rs 166 billion, but criticised doctors and medical staff, who discredited the government by frequently holding strikes and protests in hospitals. He said that the people needed to realise their responsibility, saying that if parents get their children vaccinated against polio at specified centres, then it would help save Rs 10 to 11 billion spent on Lady Health Workers (LHWs). He said that female students secure 70 seats in medical colleges, who ultimately do not prefer to serve in rural areas, which was creating problems for the government.

Prof Nisar Ahmad, Head of Pediatric Hematology and Transfusion Medicine, Children’s Hospital, Lahore, said the Punjab government’s efforts in the health sector were wasted due to paucity of trained personnel, saying the government had established a building and provided equipment but there were no medical technologists to operate the equipment. He emphasised upon the government to formulate policy in consultation with professionals in their relevant fields. He said that hemophilia patients required only a single factor among 12 to 13 factors in white blood cells of the donor. “A single donor’s blood can be used to treat four hemophilia patients,” he added.

Rana Azfar Zafar, General Manager novo nordisk, said that hemophilia patients do not get required treatment as over 90 per cent of such patients do not have access to treatment in Pakistan.

Munnoo Bhai, a senior columnist and playwright, said that mothers of 40 per cent of thalassaemia patients have been divorced by their husbands, which is the worst kind of discrimination against women. “It is highly unethical to hold women responsible for genetic diseases among their children,” he added.

Sheikh Alauddin, MPA, said that he had tabled a resolution in the Punjab Assembly about a mandatory test of couple before marriage a few years ago but it could never be made a law. “If couple are screened before marriage, they can protect their children from many genetic diseases,” he added.

Prof Salman Adil, Head of Hematology Department, AKU Hospital, Karachi, said that the administration of whole blood to a hemophilia patient was not only a waste of blood, but also may cause infection to the recipient.

Prof Samina Amanat, Association Professor of Hematology, PIMS, Islamabad, said that most patients go to hakeems and quacks and their condition was further aggravated, which was increasing the burden on government hospitals.

Masood Farid, President Pakistan Hemophilia Patient Welfare Society, said that he himself was a hemophilia patient, saying that hemophilia patients were getting international standard treatment from the platform of the Pakistan Hemophilia Patient Welfare Society.

Dr Ayesha Ehsan, Associate Professor Fatima Memorial Hospital, advocated improving BHUs and THQ hospitals to provide quality treatment services to patients in their own hometowns. Sofia Zaka said that nearly 75 per cent of hemophilia patients in the world were not getting required treatment, but the situation in Pakistan was even worse as nearly 90 per cent hemophilia patients were deprived of the treatment.

MKRMS Chairman Wasif Nagi hosted the seminar while Ali Imran Inayat and Kiran Butt assisted him.

Source : http://www.thenews.com.pk/print/121743-No-hemophilia-centre-for-120m-population-of-Punjab

Gene Therapy Helps 3 Hemophilia Patients

• Clotting protein levels rise as high as 30 percent of normal
• Drug is partnered with Pfizer, now in early-stage trial

Spark Therapeutics Inc. surged the most since October after the biotechnology company said its gene therapy helped three hemophilia B patients increase clotting ability enough to stop their regular infusion treatments.

The therapy, called SPK-9001, is co-owned by Pfizer Inc., which will take over development after Spark completes early-stage trials. The treatment gives patients a functioning copy of the gene that produces factor IX, a protein that clots blood. Spark rose 22 percent to $50.33 at 9:51 a.m. in New York, after earlier reaching $51.83.

Levels of factor IX stabilized at 28 percent of the normal level after 18 weeks in one patient and 30 percent after seven weeks in another, according to a statement from the companies Thursday. The study will be presented at the European Hematology Association’s annual meeting in June. A third patient was at 16 percent after three weeks.

Patients with more than 5 percent of the normal level are considered to have mild hemophilia, which means the bleeding is controlled unless they are in an unusual circumstance like an accident, according to Neil Frick, vice president of research and medical information at the National Hemophilia Foundation.

“You want to achieve a certain level of factor IX with consistency and durability,” without serious side effects, Spark’s Chief Executive Officer Jeff Marrazzo said by telephone. “From our perspective, it’s hitting all those things and exceeding the bar. We’re extremely excited.”

Eye Therapy

Spark, based in Philadelphia, may be one of the first drugmakers to bring a gene therapy to market in the U.S. Its lead product, a treatment for a rare inherited eye disorder, has improved patients’ visions in trials. The new data “demonstrates Spark’s ability in multiple target tissues, first in the eye and now the liver,” Marrazzo said. “That should give people confidence in our technology.”

“These are the highest levels of sustained factor IX expression that have been reported in hemophilia B gene therapy trials,” said Lindsey George, the lead researcher on the trial and an attending physician at The Children’s Hospital of Philadelphia.

George said she’s “cautiously optimistic,” and that more time is needed to prove the durability of the treatment and ensure that no safety issues appear over time.

No Bleeds

One of the three patients had a suspected ankle bleed two days after receiving treatment and gave himself an infusion. Other than that, there have been no bleeds or need for infusion for the three patients during the study period so far, according to the abstract. All the patients had severe hemophilia and needed regular infusions prior to joining the trial, said George.

UniQure NV, the Dutch biotechnology company that developed the first gene therapy approved in Europe, is also working on a treatment for hemophilia B and said in January that two patients on its treatment achieved 5.5 percent and 4.5 percent of normal.

Marrazzo said his goal is to clear the 5 percent bar by a wide margin -- “when you’re that close to the edge you run risks,” he said.

Both Spark and UniQure are still in early stages of development, and it will take years for the therapies to gain approval from the U.S. Food and Drug Administration and reach the market. Spark is also developing a gene therapy for hemophilia A, another form of the disorder that has a broader patient population. BioMarin Pharmaceutical Inc. presented early data in April showing that its hemophilia A treatment appeared to be working and safe.

Cost Question

Hemophilia B is a rare genetic disorder that affects about 4,000 males in the U.S. and 26,000 males worldwide, according to Spark. Patients currently are treated via infusions of factor IX self-administered twice a week to prevent bleeds. The treatment typically costs about $300,000 per year in the U.S., said Frick, from the National Hemophilia Foundation.

If these treatments were to come to market, “there are plenty of patients out there who would be really happy to use it as it would make a big difference in their lives,” Frick said. “The scary thing is cost -- how much will it cost and will insurance companies cover it?”

Since gene therapies are intended to be a one-time treatment that lasts a lifetime, they are expected to come with large price tags, potentially even hitting $1 million, Frick said. A representative for Spark declined to comment on a potential cost, noting that Pfizer will lead commercialization for the product, if approved.

source : http://www.bloomberg.com/news/articles/2016-05-19/spark-s-gene-therapy-boosts-clotting-in-3-hemophilia-patients