The National Hemophilia Center

Hemophilia is an X linked recessive genetic disease (see below), usually passed down from parents to children. However, in approximately one-third of all children with hemophilia, there is no family history of the disease. In these sporadic cases, it is believed that the disorder results from a new gene mutation.

Hemophilia stems from malfunction of the gene that controls the production of clotting factor 8 or 9. These particular genes are located on the X chromosome, and hemophilia is therefore much more common in males and rarely occurs in females.

The genetics of hemophilia are as follows:

• A female carrier of hemophilia has the abnormal gene on one of her X chromosomes. When she is pregnant, there is a 50/50 chance of her passing on the hemophilia gene. If the gene is passed on to a son, he will have hemophilia. If the gene is passed on to a daughter, she will be a carrier.
• If a father has hemophilia but the mother is not a carrier, then none of the sons will have hemophilia. However, all of the daughters will be carriers.

There are two main forms of hemophilia:

1. Hemophilia A – this is the most common type of the disease, accounting for about 85% of all cases. It is caused by a deficiency of blood clotting factor 8.
2. Hemophilia B – caused by low levels of blood clotting factor 9.

As a bleeding disorder, the primary symptom of hemophilia may be uncontrolled bleeding. In Israel Hemophilia may be diagnosed due to post circumcision bleeding, in the 8th day of life. The severity of hemophilia symptoms is dependent largely on the amount of clotting factors in the individual’s blood. In mild cases, people may not be aware that they have hemophilia until a surgery or major injury complicated by bleeding. In contrast, someone with severe hemophilia may bleed spontaneously, with no known reason. When this occurs in a joint, such as the elbow, knee, hip, shoulder or ankle, it can be very painful. Repeated joint bleeds lead to chronic synovitis and orthopedic damages, requiring jpoint replacement surgeries, at young age.

The most common symptoms of hemophilia include:

• Bleeding that does not stop after circumcision
• Bruising, from even minor accidents, that may lead to skin hematoma
• Bleeding into a joint
• Bleeding into muscles
• Bleeding internally- usually following trauma. Brain bleeds may occur following delivery and may be fatal
• Bleeding in the urine or stool
• May occur yet is much less frequent as compared to joint and muscle bleeds

At the National Hemophilia Center at Sheba, we offer integrative, individualized treatments for hemophilia. We monitor each patient closely to recommend the most appropriate medical therapies. Presently, the standard treatment involves receiving regular intravenous infusions of coagulation concentrates to promote blood clotting and reduce bleeding. Novel non-replacement therapies are also offered at the center, wither as a registered treatment or within large international multicenter trials. However, research into the use of gene therapy to eradicate hemophilia may offer a new, revolutionary treatment.

Hemophilia gene therapy, based on genetic engineering, is breaking new ground as a way to treat the disease for life with just a single dose. This experimental treatment uses the common adenovirus to deliver a healthy copy of a gene to compensate for the defective gene that is responsible for this coagulation disorder. Given by infusion, the virus travels to the liver, where the healthy gene is “unloaded” from the virus. This gene then permeates the liver cells, divides, and multiplies – thereby curing hemophilia through the subsequent production of clotting factors.

Ultimately, the goal is to administer just one dosage of this innovative treatment to eradicate hemophilia. So far, the results are dramatic and promising – however, not everyone is a suitable candidate for gene therapy. For example, children cannot receive the treatment because their liver tissue is still developing, and patients with liver illnesses or antibodies directed against blood clotting factors, or patients with antibodies towards the specific viral carrier, are also not suitable candidates.