Youngsters with Hemophilia

by Food and Drug Administration (FDA)

The outlook for a child with hemophilia is brighter today than ever before. A string of scientific and technological marvels has produced dramatically safer and more effective treatments for this blood-clotting disorder, and some authorities believe that a cure may be available by the year 2000. For 20,000 Americans afflicted with hemophilia, their families, and a small army who help people cope with this devastating illness, that would indeed be the millennium. Some scientists, however, caution that formidable obstacles will have to be overcome before the hope of a cure becomes a reality. But scientists and those who provide care for people with hemophilia agree that new antihemophilic agents recently licensed by FDA are not only effective, but also safer than any earlier treatments.

To understand the progress in hemophilia treatment and to appreciate why molecular biologists and other scientists believe they're on the road to a cure, you have to know something about bleeding and what makes it stop, about genes that cause and might one day cure bleeding disorders, and about steps taken to prevent a repetition of the conditions that allowed thousands of people with hemophilia to be exposed to AIDS.

A Process Gone Awry

When most of us think of bleeding, our image is a stream of red serum exiting the body in response to an injury through skin that is normally intact. But injuries also commonly cause bleeding inside the body — bleeding we may neither see nor feel. In healthy individuals, a minor bump can damage blood vessels, causing blood to leak into the surrounding tissue and producing a bruise. A process called hemostasis plugs the hole in the damaged vessel and forms a clot that stops the blood loss and limits the size of the bruise.

Basically, this is how hemostasis works. When a blood vessel is punctured, circulating blood components called platelets seek out and adhere to the damaged part of the vessel wall. Other platelets then clump at the site to form a plug, the initial step in hemostasis. Then, more than a dozen separate proteins in plasma, the fluid portion of blood, work together to form a clot that completes the process and stops the bleeding. The small amount of blood that escapes during the bleed gets absorbed and disposed of, and the body goes on functioning normally.

In people with hemophilia and related blood-clotting problems, however, bleeding can take a very different course. For them, hemostasis doesn't work normally because one or another of the blood proteins, or factors, that collaborate to repair damaged vessels and form clots is defective, deficient, or totally absent.

The idea that people with hemophilia can bleed to death from a minor cut or injury is a misconception. In fact, external bleeding is seldom a serious problem for hemophiliacs. They may bleed somewhat longer than other people, but minor bleeding episodes can generally be controlled by ordinary first-aid measures.

On the other hand, unchecked internal bleeding can be serious — even life-threatening — for a person with hemophilia. Blood that leaks into the knee joint, a common site of internal bleeding, can cause painful swelling. Repeated bleeding eventually destroys cartilage that enables the knee to work smoothly and easily. The joint becomes permanently stiff and painful, the result of hemophilic arthritis. Other joints — the ankle, wrist or elbow — can be similarly affected by internal bleeding. Patients can also bleed into muscle and other soft tissue. If unchecked internal bleeding involves air passages or the brain or other vital organs, the patient's life is in grave danger.

Historic Insights

The cause of hemophilia and other blood-clotting disorders is well understood. In hemophilia, the problem lies with one of the factors responsible for forming blood clots. The most common type of hemophilia, affecting about 17,000 Americans, is associated with factor VIII. About another 2,800 people in this country have hemophilia related to factor IX, and an estimated 200 others have problems with clotting factors VII, X, XI, or XIII. Probably the most common hereditary bleeding disorder is von Willebrand disease, a somewhat milder illness caused by failure of the factor that makes platelets clump together to plug damaged blood vessels.

An illness like the one we now know as hemophilia was recognized in antiquity, and in the fifth century A.D. Jewish rabbis decreed that newborn males were exempt from the requirement to be circumcised if they had brothers or uncles who had bled to death following circumcision. They apparently had an inkling of what we now know to be the case — that hemophilia is an inherited disease passed from mothers — carriers of the disease — to their sons, and very rarely to their daughters.

By 1840, transfusion had been successfully used to treat hemophilia. Popular and scientific interest in hemophilia soared when Queen Victoria's son, Prince Leopold (born in 1853) was found to suffer from the bleeding disease, which meant that the queen was a carrier. Two of Victoria's daughters also proved to be carriers and transmitted the disease through marriage to the royal families of Russia, Germany and Spain.

In this century, advances in genetics, molecular biology, and biotechnology have greatly expanded understanding of hemophilia and its treatment. Investigators learned in 1936 that the substances needed to clot blood are found in plasma. That discovery led to easier and more effective treatment. Patients could be given fresh plasma, rather than whole blood, to control bleeding.

In the mid-1960s, Judith Graham Pool, M.D., discovered a technique for concentrating factor VIII from plasma. Purified plasma concentrates produced from the pooled blood of thousands of individual donors became available in the late 1960s. By the early 1970s, the availability of freeze-dried plasma concentrate meant that patients could be treated at home at the first sign of internal bleeding. This sharply reduced the need for hospitalization and lowered the risk of crippling joint or tissue damage. For the first time, children and adults with hemophilia were able to lead virtually normal lives at home, at school, and at work. What has been called "the golden age" of hemophilia had arrived. It didn't last long.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.