Hemophilia is an inherited bleeding disorder that affects mostly males. Blood contains many proteins, called clotting factors, which work to stop bleeding. In people with bleeding disorders, these clotting factors are missing or do not work as they should. The lack of clotting factor causes people with hemophilia to bleed for longer periods of time than people whose blood factor levels are normal or work properly.
People with hemophilia do not bleed faster than other people, and will not bleed to death from a minor cut or injury. The main problem for people with hemophilia is bleeding internally, mainly into muscles and joints. Clotting factors are proteins in the blood that make blood clot. There are 13 main factors (identified by roman numerals) that work together to produce a clot. If one factor is missing, the chain reaction is broken, clots will not form properly, and bleeding will continue.
People with mild hemophilia may have very few bleeding episodes, and may only need to take precautions if they are having surgery or are seriously injured. However, people with severe hemophilia often bleed spontaneously (that is, there is no obvious cause for the bleed, it just happens).
With treatment products and proper care, people with hemophilia can live perfectly healthy lives. Without treatment, hemophilia can cause crippling pain, severe joint damage, disability, and early death. Tragically, only about 25 percent of people with hemophilia in the world receive adequate treatment.
Genetics of Hemophilia
Hemophilia is a genetic disorder, which is usually inherited. It cannot be caught or transmitted. The hemophilia gene is passed down from a parent to a child. Men with hemophilia pass the gene on to their daughters, but not to their sons.
Women do not usually have hemophilia, but they can be carriers of the gene. Women who are carriers have a 50 percent chance of having a boy with hemophilia and a 50 percent chance of having a girl who is a carrier.
About one third of new cases are caused by a spontaneous mutation of the gene, which means that there was no history of hemophilia in the family before.
Levels of severity
The severity of hemophilia is determined by the level of clotting activity of factor VIII or factor IX in the blood. There are three levels of severity: mild, moderate, and severe. The following table shows the range of factor VIII and factor IX activity:
| Level | Hemophilia Severity | Percentage of normal factor activity in blood Number of international units (IU) per milliliter (ml) of whole blood |
|---|---|---|
| normal range | 50%-200% | 0.5–2 IU |
| subnormal range, but bleeding after injury is unlikely | 25%-49% | 0.25–0.49 IU |
| mild hemophilia | 6%-24% | 0.06–0.24 IU |
| moderate hemophilia | 1%-5% | 0.01 –0.05 IU |
| severe hemophilia | less than 1% | less than 0.01 IU |
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 the bleeding just happens with no obvious cause.
People with moderate hemophilia bleed less frequently, usually after an injury, perhaps once a month. 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. They may never have a bleeding problem.
Treatment for hemophilia
Hemophilia is treated by replacing the missing clotting factor in the blood. This is done by injecting a product that contains the needed factor into a vein. Bleeding stops when enough clotting factor reaches the bleeding site. When bleeding is into a joint it is very important that treatment is given as quickly as possible to prevent long-term damage.
Clotting factors are found in the following treatment preparations in order of increasing concentration:
· whole blood
· plasma
· cryoprecipitate
· factor concentrates
Historically these first three have been used in the treatment of hemophilia.
In the U. S. factor concentrates are used exclusively for Hemophilia A and Hemophilia B due to the increased safety and ease of use of these products over the whole blood or fractions of blood--plasma and cryoprecipitate.
Factor concentrates are very effective but are expensive. They can be made from human blood (called plasma-derived products) or manufactured using genetically engineered cells that carry a human factor gene (called recombinant products). There are several levels of purity (the concentration of factor) ranging from intermediate to very high depending on the manufacturing process. The therapeutic safety of each product depends on the methods used to prevent, remove, or inactivate viruses that may be present in the source plasma.
People with mild hemophilia A sometimes use desmopressin (also called DDAVP), a synthetic hormone that stimulates the release of factor VIII.
Gene therapy in hemophilia
There is no cure for hemophilia yet but gene therapy remains an exciting possibility and holds out the prospect of a partial or complete cure for hemophilia. There are many technical obstacles to overcome, but it is encouraging to see that clinical trials for both factor VIII and IX have begun.
Genetics of hemophilia
Hemophilia usually only affects men, because the hemophilia gene is carried on the same chromosome that determines whether a person is male or female. The chromosomes that determine a person’s sex are called X and Y. Men have an X and a Y chromosome and women have two X chromosomes.
The genes for hemophilia A and B are on the X chromosome. Because women have two X chromosomes, if one does not work properly, the other X chromosome makes up for it. However, if a women has the hemophilia gene on both X chromosomes, then she will have hemophilia.
Difference between hemophilia A and hemophilia B
There are two types of hemophilia: hemophilia A (also called Factor VIII deficiency) and hemophilia B (also called Factor IX or Christmas disease). Both are caused by a lack or absence of one of the proteins in the blood (called factors) that control bleeding. Hemophilia A is caused by a deficiency of factor VIII, and hemophilia B is caused by a deficiency of factor IX.
There is no difference between the two types of hemophilia, except that hemophilia B is about five times less common than hemophilia A. Approximately 75 – 80% of all persons with hemophilia have Factor VIII deficiency and most of the remainder have Factor IX deficiency or Hemophilia B. There are also a small number of persons missing other factors used by the body for clotting. These rare disorders comprise the remainder of the persons diagnosed with hemophilia.
Hemophilia diagnosis
Hemophilia is diagnosed by measuring the level of factor activity in the blood. 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 fetal blood sampling at a later stage (18 or more weeks).
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.
These tests can be done at a hemophilia treatment center. A list of treatment centers around the world is accessible from the World Federation of Hemophilia web site. See the resources section for the directory.
The U. S. centers are located at the Centers for Disease Control and Prevention website also listed in the resources section.
Bleeding in hemophilia
Most bleeding in hemophilia occurs internally, into the joints or muscles. The joints that are usually affected are the ankle, knee, hip, elbow, and shoulder. Repeated bleeding without prompt treatment can damage the cartilage and the bone in a joint, leading to chronic arthritis and disability. Muscle bleeds most commonly occur in the upper arm, forearm, upper leg, calf, and iliopsoas muscle (the front of the groin area).
Some bleeds can be life-threatening and require immediate treatment. These include bleeds in the head, throat, gut, or iliopsoas.
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 there is swelling, numbness, or a tingling feeling along with the bruising. If any of these symptoms are experienced, contact your physician or local hemophilia treatment center.
Exercise and sports in hemophilia
Some people with hemophilia do not exercise because they think it may cause bleeds, but exercise actually helps prevent bleeds. Strong muscles help protect someone who has hemophilia from spontaneous bleeds and joint damage.
Sport is an important activity for young people. It not only helps build their muscles, it helps them develop mental concentration and coordination, and learn about being part of a team. 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 sports that most people with hemophilia can safely participate in, whilst sports like football, rugby, hockey and boxing are not recommended for people with hemophilia.
Inhibitors in hemophilia
Inhibitors are antibodies to factor VIII or factor IX that attack and destroy the factor VIII and IX proteins in clotting factor concentrates, making treatment ineffective. They appear almost exclusively in patients with severe hemophilia. There is some controversy over the precise incidence (number of new cases) of inhibitor development, but it is generally accepted that around 15 percent of people with severe hemophilia A will develop inhibitors at some stage. By contrast, inhibitor development in hemophilia B is very rare indeed, and seen in less than one percent of subjects. Most inhibitors emerge after relatively few treatments. In general, the more treatments a person has had without developing inhibitors, the less likely he is to develop an inhibitor.
Prophylaxis
Prophylaxis is the regular use of clotting factor concentrates to prevent bleeds before they start. Injections of clotting factor are given two or three times a week to maintain a constant level of factor VIII or IX in the bloodstream. It can help reduce or prevent joint damage. In countries with good access to 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).
Venous access devices (port-a-cath)?
A port-a-cath, or implantable venous access device (IVAD), is implanted under the skin, usually in the upper chest but there are models which can be inserted into the arm. It has a small metal reservoir with a rubber diaphragm which is connected to a catheter which is then threaded into a large vein in the chest or arm. The entire device is surgically implanted under the skin so there is no catheter that hangs out of the body. The device provides ready access to a vein for administering medications and fluids intravenously. It can also be used for drawing blood samples.
The device is accessed by inserting a special needle through the skin and into the rubber diaphragm of the reservoir. The medication or fluid is injected into the device and it flows through the catheter into the vein.
These devices have made prophylaxis in hemophilia much easier for families because the problems of "finding a vein" for infusion two to three times a week are eliminated. However, there are risks involved with their use, the most worrisome being that of infection. Studies differ but some show an infection rate as high as 50 percent. These infections can usually be treated with intravenous antibiotics but sometimes the device must be removed. Also, there are other studies that show a risk of clots forming at the tip of the catheter. Still, many families have chosen to use the device in spite of the risk because of the benefits. Like any other procedure, one must weigh the risks and benefits.
What is von Willebrand disease?
von Willebrand disease is an inherited bleeding disorder, similar to hemophilia, but the two disorders are not the same. vWD is the most common inherited clotting disorder, affecting both men and women. It has been estimated that vWD affects up to one percent of the population. However, it is generally the least severe of the clotting disorders.
vWD is caused by a deficiency or defect of a blood clotting protein called von Willebrand factor (vWF), a gluelike protein that helps platelets in the blood stick together and seal off tears in injured blood vessels. This is called a platelet plug. If a person does not have enough vWF or it does not work properly, no platelet plug will form and bleeding will continue for a longer period of time.
Most people with vWD will have few, if any, symptoms. The main symptoms are easy bruising, frequent or prolonged nosebleeds, heavy or prolonged menstrual bleeding, and prolonged bleeding following injury, surgery, dental work, or childbirth.
vWD is treated with desmopressin (also called DDAVP) or with infusions of a clotting factor concentrate that contains vWF.
Frequently Asked Questions was originallly published by the World Federation of Hemophilia and isused here with its permission. It cannot be reproduced elsewhere without the prior written permission of the WFH.