The Hematology Services offered at Hospital Donostia, Guipuzcoa’s main treatment center for congenital bleeding disorders, provide patients with comprehensive care for any coagulopathic problems.
Recently diagnosed patients: When there exists the possibility the illness has been transmitted or when a carrier wishes to get tested, Hematology orders the appropriate diagnostic test from the hospital’s Genetics Unit. Once the analysis has been completed, a meeting is held with the affected person to inform them about the disease’s characteristics as well as the likelihood of having contracted it. In addition, the supervising physician informs patients of the Psychology Services offered to all hemophiliacs by the Hemophilia Association of Guipuzcoa.
Bleeding episodes: Whenever a hemophilic individual seeks treatment for hemarthrosis or any other type of bleeding, they are given the appropriate amount of clotting factor in order to stop the bleeding. If the hematologist is able to rule out other associated pathologies, the patient is referred to the corresponding hospital service, be it Hematology or another department, so that the problem can be handled until the patient has fully recovered.
Watching the illness: as long as there are no complications associated with the bleeding disorder, the patient will be considered a healthy and treated as such. Interdepartmental communication: the very nature of this illness demands there be a strong working relationship with the other hospital departments.
Multidisciplinarity: The hospital’s Hematology and Rehabilitation Services Departments, along with the supervising physician of the Hemophilia Association’s Psychology Services, carry out periodic check-ups on patients in an effort to provide them with the best care possible.
Haemophilia is not a new disease, haemophilia is known from ancient times. The first written references related to circumcision are described in the Talmud, IInd Century.
Hemophilia is an inherited bleeding disorder that affects mostly males, because the hemophilia gene is carried on the same chromosome that determines whether a person is male or female. 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. 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. The World Federation of Hemophilia works to improve the level of treatment and care around the world.
Under the name of congenic coagulopathies it has been discribed several coagulation factors (factor II, Factor V, factor VII, factor X, etc.) So we differentiate different types of haemophilia:
Haemophilia A, caused by a lack or absence of factor VIII that controls bleeding definida por la deficiencia de factor VIII. Es la más frecuente tanto en el ámbito nacional como internacional, representando un 85% de los casos censados.
Haemophilia B (also called Christmas disease), caused by a lack or absense of the protein in the blood called factor IX. von Willebrand disease or Haemophilia C caused by the lack or absence of various coagulation factors.
The haemophilia severity 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//Percentage of normal factor activity in blood//Number of international units (IU) per millilitre (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; mild haemophilia=6%-24% //0.06-0.24 IU;moderate haemophilia=1%-5%//0.01-0.05 IU;severe haemophilia less than 1% and less than 0.01 IU
People with severe haemophilia 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 haemophilia bleed less frequently, usually after an injury, perhaps once a month. Cases of haemophilia vary, however, and a person with moderate haemophilia can bleed spontaneously. People with mild haemophilia usually bleed only as a result of surgery or major injury. They may never have a bleeding problem.
At the beginning of life, babys have not important clinic problems. If it is necessary to do a blood test the extraction should be done with the most care to avoid hematoma. It is also needed an special care when vaccination. When baby begin to walk hematomas in legs and gluteus will be frequent. Al empezar a caminar, los hematomas en las piernas y glúteos serán más frecuentes. When dentition they can have bucal bleeeding. But the worse bleeding is when the frenum is broken. 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 centre.
Mucouse mebrane bleeding Although mucouse bleeding is not so severe, often requires treatment. The most frequent bleedings are in nose, gum, or when losing of the first dentition.
Muscles and joint bleeding 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.
Cerebral bleeding It can be spontaneous. Nevertheless, usually it appears when there is a traumatism. The most common manifestations are: headache, vomiting, and losing consciousness. Sometimes, also motor muscles deficiency and coordination disorder. It is necessary to take the deficient factor as soon as possible and in some cases it is also necessary surgical treatment.
Urinal bleeding Spontaneous haematurias are not frequent in people with haemophilia. Generally is not necessary to take the specific treatment, but rest and hydration could be enough.
Von Willebrand disease is the most commonly inherited bleeding disorder and, most people have it in the mild form. It may be detected at any age and it affects both men and women. Von Willebrand disease occurs when there is a problem with one of the body’s clotting factors- the one known as von Willebrand. Von Willebrand disease is a group of genetic bleeding disorders in which the common clinical finding is a prolonged bleeding time.
During recent years, evidence would seem to indicate that von Willebrand disease is a variety of heterogeneous diseases in which the amount and/or function of von Willebrand factor, in plasma and/or platelets is abnormal, and the activity and concentration of plasma Factor VIII is lowered to varying degrees.
Von Willebrand’s disease is divided into three types based on the amount of von Willebrand factor in the blood and how well it works.
Type I is the most common type. Von Willebrand factor works well but there is not enough of it in blood.
Type II von Willebrand’s disease have enough vojn Willebrand factor, but it does not work properly. Depending on why it does not work, these people are classified as either Type IIA or Type IIB.
Type III von Willebrand’s disease occurs when people have almost no von Willebrand factor in their blood. This is most severe form of von Willebrand disease.
1. The importance of the von Willebrand factor Bleeding is usually controlled in two steps. In the first, a platelet plug has to form. In the second, a blood clot develops. Von Willebrand factor must be present in the blood for a platelet plug to form; without it, this first step in clotting can’t take place.
In many patients with von Willebrand disease, another clothing factor-called factor eight (factor VIII) is also affected. (A significant lack of factor VIII is the cause of haemophilia A). Without enough factor VIII, the other clotting factors can’t form a firm clot, so the second step in clotting takes much longer.
When someone with von Willebrand’s disease is injured and bleeds, the bleeding takes a longer time to stop because clots form more slowly. This is especially true in mucosal bleeding, which occurs in mucous membranes- the delicate tissues that line the nose, mouth, reproductive organs, and gastrointestinal (GI) tract. Nosebleeds, menstrual bleeding, and bleeding from dental extractions are often prolonged due to improperly functioning platelets that are essential to forming clots.
2. How mild to moderate von Willebrand’s disease is diagnosed Mild to moderate von Willebrand’s disease is often diagnosed when there’s a history of bleeding problems in one or more family members.
In women, it’s often first recognized because unusually heavy menstrual bleeding at the time their monthly period, a condition called menorrhagia. This condition is another form of mucosal bleeding because the lining of the uterus is made up of mucous membrane. Menorrhagia is a common complaint among women, yet von Willebrand’s disease isn’t usually suspected as the cause.
There are many causes of menorrhagia, and most are problems of a gynaecologic nature. Because these causes are usually suspected before von Willebrand’s disease, the symptom of menorrhagia is often treated with hormone therapy, which may correct the problem. However, while these patients are receiving effective treatment for menorrhagia, they may remain undiagnosed for the true underlying cause. This is a good example of why many patients with von Willebrand’s disease go undiagnosed.
Other signs and symptoms: - bruising easily. - repeated nosebleeds. - prolonged or excessive bleeding following minor surgery, such as having a tooth pulled or tonsils removed. While it is fairly common, von Willebrand’s disease con be difficult to diagnose. This is because many of its mild symptoms can appear to be symptoms of other illnesses. In fact, it is often so mild that many people go undiagnosed for years, and some remain undiagnosed all their lives. While only about 5.000 people are known to have von Willebrand’s disease, it’s estimated that more than 1% of the population, or 2.5 million people in the US, may have it and not know it.
3. What causes von Willebrand’s disease Von Willebrand’s disease is usually inherited. The colour of the hair or eyes, how tall we are, or our voice, can all be inherited. The kind of blood we have is also inherited. On rare occasions, von Willebrand’s disease can also be acquired. This means that a person can develop the disorder later in life even if they are not born with it.
4. How von Willebrand’s disease may affect your lifestyle In some cases, your doctor may want you to think more carefully about the activities you want to participate in, and there may be a few things you’ll want or need to avoid. Playing sports is a good example. Depending on your doctor’s advice, you may want to avoid rough contact sports, such as football or hockey. Other sports, however, such as swimming, basketball, softball, and tennis, may be fine.
The basic rules are these:
a) Follow your doctor’s advice.
b) Take your medication as directed.
c) Use common sense.
If you have a fever, a headache, or other aches and pains, don’t take aspirin or any other product that has aspirin in it without first consulting your doctor. Many over-the-counter cold and pain medicines contain aspirin. If you are not sure, check with your doctor or pharmacist before taking anything. Aspirin should be avoided because it can affect how your blood platelets function, and if they don’t function normally, thi9s can lead to more difficulties with the formation of platelet plugs to control bleeding. Of course, you’ll need to consult your doctor regarding any special precautions that should be taken before surgical procedures.
5. How von Willebrand’s disease is passed along Von Willebrand’s disease is the most common hereditary hemorrhagic disease in humans. However the true prevalence of von Willebrand’s disease is difficult to establish as clinical manifestations of this disease vary and milder cases are often not recorded. Recent studies suggest that as many as 1-3% of the population may have this disorder.
Learning about the genetics of von Willebrand’s disease can help you understand how you came to have it and can help you predict whether your children may also have it. As you may know, you receive a set of chromosomes from each of your parents that includes one X and one Y. These are referred to as the “sex” chromosomes. Boys receive an X chromosome from their mother and a Y chromosome from their father; girls receive an X chromosome from each parent. These play an important part in the genetic traits that children inherit.
In sex-linked inherited disorders (such as haemophilia), the X chromosome carries the gene that determines if a child has the disorder. Since girls get two X chromosomes, even if one of them carries an affected gene they have an unaffected X chromosome to make up for it. As a result, they usually don’t show signs of the disorder. Girls do, however, serve as carriers of these diseases and may pass them along to their children. On the other hand, because boys get only one X chromosome, they are dependent on the genes it contains.
Therefore, if the X chromosome they inherit has an affected gene on it, they’re more likely to have sex-linked disorders. Von Willebrand’s disease, however, is not sex-linked. It’s carried on one of the non-sex, or autosomal, chromosomes (chromosome 12). Because of this, both boys and girls have an equal chance of inheriting von Willebrand’s disease. Von Willebrand’s disease can affect persons of either sex with a positive maternal or paternal history. Bleeding manifestations will be mild to moderate and include easy bruising, intermittent bleeding from small skin cuts over prolonged period and abnormal bleeding after surgical procedures (e.g. tooth extraction). The level of plasma von Willebrand factor can be temporarily elevated by vasoactive stimuli induced by stress or exercise.
Also hormonal changes associated with stress or pregnancy and an acute phase response to inflammation or infection stimulate increased synthesis of von Willebrand’s disease, which also elevates von Willebrand’s factor levels in plasma. Thus, in persons with mild von Willebrand’s disease, plasma level variations may cause screening test to be normal on some occasions and abnormal on others, making diagnosis difficult. Von Willebrands disease appears to follow a pattern that helps predict who may inherit it:
One parent with mild to moderate von Willebrand’s disease results in 50% chance that their children will have the disorder in the same severity.
Two parents with mild to moderate von Willebrand’s disease results in a 50% chance that their children will have the disorder in the same severity, and s 25% chance that they will inherit the disorder in its severe form.
It ‘s possible for inherited von Willebrand’s disease to be diagnosed in someone when neither of their parents has the disorder. This is referred to as a new mutation. If this occurs, the pattern of inheritance is the same as in someone who has the family history of the disorder.
The story of von Willebrand’s disease begins on Föglö Island in the Aland Archipelago of Finland in 1924. A physician by the name of Erik Adolf von Willebrand was called to examine a 5-year-old girl who appeared to have some sort of bleeding disorder. Dr. von Willebrand examined not only the girl, but many members of her large family as well. Over the course of several years, he found that 23 of 66 family members had a similar bleeding problems.
1. How Dr. Von Willebrand knew it wasn’t haemophilia Dr. von Willebrand noticed several things that caused him to realize this disorder was not haemophilia. First, this disorder affected both males and females equally, unlike haemophilia, which almost always affects only males. Second, his laboratory work showed that while these people had the normal number of platelets, the platelets didn’t function properly, and the time it took these patients to stop bleeding was prolonged. Also, bruising was most common in these patients, as opposed to the muscle or joint bleeding that is common in haemophilia. He called this odd disease pseudo-haemophilia, or “false” haemophilia. The disease eventually came to be known as von Willebrand’s disease.
2. What we have learned since then In the 1950s, it was discovered that the blood of people with von Willebrand’s disease didn’t have normal amounts of factor VIII. Also, the blood platelets of these patients could not stick to damaged blood vessels, due to some missing ingredient. This ingredient in the blood was termed von Willebrand factor. It was learned that in addition causing the platelets to stick , von Willebrand factor also serves as the protein that carries and protects factor VIII in the bloodstream. So, if the blood lacks von Willebrand factor, there may also be a shortage of factor VIII. Without factor VIII, the second step of clotting won’t occur properly.
For many years, the only treatment for patients with von Willebrand’s disease was a blood transfusion.
Then, in the 1960s, it was discovered that a special liquid could be separated out from donated plasma (the liquid portion of the blood) by freezing and thawing techniques. This liquid, called cryoprecipitate contains a higher concentration of the clotting factors needed to treat certain diseases.
Unfortunately, although better than using either whole blood or plasma, cryoprecipitate continued to expose patients to other unneeded parts of the blood, which could cause additional problems. This therapy also exposed patients to the risk of viruses that could be present in the donated blood.
Over the past decade, newer products have been created using a variety of methods to minimize these risks, and these methods continue to be improved upon today. The new products, called factor VIII concentrates, are made up mostly of factor VIII. However, a few of these products also contain enough von Willebrand factor that they are used to treat von Willebrand’s disease.
Today doctors generally recommend that only patients with more severe forms of von Willebrand’s disease and those with mild von Willebrand’s disease who have undergo extreme medical procedures (like certain types of surgeries) continue to use these concent
Due to the importance of the subject and its repercussions, the opinion of the Haemophilia Society of Guipuzcoa - ASHEGUI- about treatments and factors is related to the scientific point of view which works will be published periodically. Without any doubt our reference will be the scientific and medical criteria. Therefore, we show the following publications that we consider of great interest:
Plasma derived and Biotech products
Trasmissible Agents and Safety of coagulation factor concentrates