Types of Disorders

Hemophilia

Hemophilia A is the most common type of hemophilia.  It is also known as factor VIII  deficiency or classic hemophilia. It is largely an inherited disorder in which one of the proteins needed to form blood clots is missing or reduced. In about 30% of cases, there is no family history of the disorder and the condition is the result of a spontaneous gene mutation.

Approximately one in 5,000 males born in the United States has hemophilia. All races and economic groups are affected equally.
 
When a person with hemophilia is injured, he does not bleed harder or faster than a person without hemophilia, he bleeds longer. Small cuts or surface bruises are usually not a problem, but more traumatic injuries may result in serious problems and potential disability (called “bleeding episodes”).

There are different levels of hemophilia: mild, moderate, and severe:

  • People with mild hemophilia (6% to 49% factor level) usually have problems with bleeding only after serious injury, trauma, or surgery. In many cases, mild hemophilia is not discovered until an injury or surgery or tooth extraction results in unusual bleeding. The first episode may not occur until adulthood. 
  • People with moderate hemophilia, about 15% of the hemophilia population, tend to have bleeding episodes after injuries. They may also experience occasional bleeding episodes without obvious cause. These are called “spontaneous bleeding episodes.”
  • People with severe hemophilia, about 60% of the hemophilia population, have bleeding following an injury and may have frequent spontaneous bleeding episodes, often into the joints and muscles. 

Everyone inherits two sex chromosomes, X and Y, from his or her parents. A female inherits one X chromosome from her mother and one X chromosome from her father (XX). A male inherits one X chromosome from his mother and one Y chromosome from his father (XY). The gene that causes hemophilia is located on the X chromosome.

A woman who gives birth to a child with hemophilia often has other male relatives who also have hemophilia. Sometimes, a baby will be born with hemophilia when there is no known family history. This means either that the gene has been “hidden” (that is, passed down through several generations of female carriers without affecting any male members of the family) or the change in the X chromosome is new (a “spontaneous mutation”). 

There are four possible outcomes for the baby of a woman who is a carrier. These four possibilities are repeated for each and every pregnancy:

  1. A girl who is not a carrier 
  2. A girl who is a carrier
  3. A boy without hemophilia
  4. A boy with hemophilia

With each pregnancy, a woman who is a carrier has a 25% chance of having a son with hemophilia.  Since the  father’s X chromosome determines the baby will be a girl, all the daughters of a man with hemophilia will be carriers. None of his sons, which is determined by the father through his Y chromosome, will have hemophilia. 

Genetic counseling is available at most HTCs. These professionals have information to help you make family planning decisions.

In general, small cuts and scrapes are treated with regular first-aid: clean the cut, then apply pressure and a band-aid. Individuals with mild hemophilia can use a non-blood product called desmopressin acetate (DDAVP) to treat small bleeds. Deep cuts or internal bleeding, such as bleeding into the joints or muscles, require more complex treatment. The clotting factor missing (VIII or IX) must be replaced so the child can form a clot to stop the bleeding.

Some factor products are made from human blood products such as donated plasma. Others, called “recombinant factor,” are made in a laboratory and do not use human blood products. The Medical and Scientific Advisory Council of the National Hemophilia Foundation encourages the use of recombinant clotting factor products because they are safer. Your doctor or your HTC will help you decide which is right for you. All factor treatments are injected or infused directly into the veins.

In cases of severe hemophilia, doctors sometimes recommend giving a regimen of regular factor replacement treatments (a therapy called prophylaxis) to prevent bleeding episodes before they happen. The Medical and Scientific Advisory Council of the National Hemophilia Foundation recommends prophylaxis as optimal therapy for children with severe hemophilia A and B.

Notify your doctor or HTC if your child does not respond to the usual dose of factor. In rare instances, people can develop an inhibitor, to standard factor treatment.  In the event this occurs, your doctor or HTC will work with you to develop a special plan of care.
 

Hemophilia B is the second most common type of hemophilia.  It can also be known as factor IX deficiency, or Christmas disease.  It was originally named “Christmas disease” for the first person diagnosed with the disorder back in 1952.  

It is largely an inherited disorder in which one of the proteins needed to form blood clots is missing or reduced. In about 30% of cases, there is no family history of the disorder and the condition is the result of a spontaneous gene mutation.

Hemophilia B is far less common than Hemophilia A.  Occurring in about one in 25,000 male births, hemophilia B affects about 3,300 individuals in the United States.  All races and economic groups are affected equally.

Today, factor IX concentrates are the mainstay of treatment for those with hemophilia B, just as factor VIII concentrates are for hemophilia A.  In cases of severe hemophilia, doctors sometimes recommend giving a regimen of regular factor replacement treatments (a therapy called prophylaxis) to prevent bleeding episodes before they happen. The Medical and Scientific Advisory Council of the National Hemophilia Foundation recommends prophylaxis as optimal therapy for children with severe hemophilia A and B.

Notify your doctor or HTC if your child does not respond to the usual dose of factor. In rare instances, people with hemophilia B can develop an inhibitor to standard factor treatment.  Only about 3-5% of patients with severe hemophilia develop an inhibitor, a much lower incidence than in severe hemophilia A.  However, anaphylactic reactions have occurred in some patients with hemophilia B inhibitors. 

Other Factor Deficiencies

There are ten clotting factors that are necessary in forming a blood clot.  Deficiencies in factors VIII and IX are well known to most people, but what of the other factor deficiencies?  Not everyone is as familiar with these conditions because they are diagnosed so rarely.  To date, deficiencies in eight of the lesser known coagulation factors have been documented in the medical literature.  Many of these disorders were only discovered or described within the last 40 years. 

In most cases, rare factor deficiencies are not genetically sex-linked.  They occur in equal frequency among men and women.  By and large the gene is passed down in an autosomal recessive fashion.  This means that when the factor deficiency is inherited from only one parent, the child will be a carrier of the condition, but usually not have symptoms.  It is possible for people to inherit a gene from both parents, but this happens very rarely and usually means a more severe manifestation of the disease. 

Obtaining a detailed family history is an important component to diagnosing the condition.  Most people with rare factor deficiencies are best seen by hematologists at hemophilia treatment centers.  Making a proper diagnosis for some of these rare conditions requires a quality lab and an experienced hematologist.  To find a treatment center located closest to you, click here. 

Not all factor deficiencies have the same severity.  Not everyone with these disorders needs treatment.  However for those who do, the treatments available for people with rare factor deficiencies are not optimal.  Many people in the United States with rare factor deficiencies need to take fresh frozen plasma, prothrombin complex concentrates (PCCs) or cryoprecipitate.   

Since there are such a small number of patients with these conditions, there are few clinical studies regarding the use of products to treat them.  Without solid clinical data, obtaining FDA approval for products is extremely difficult.  Very few pharmaceutical companies will choose to invest the research dollars needed to produce such products for so few patients.

Von Willebrand Disease

Von Willebrand Disease is a bleeding disorder caused by a defect or deficiency of a blood clotting protein, called von Willebrand Factor. The disease is estimated to occur in 1% to 2% of the population. The disease was first described by Erik von Willebrand, a Finnish physician who reported a new type of bleeding disorder among island people in Sweden and Finland.

Von Willebrand Factor is a protein critical to the initial stages of blood clotting.  This glue-like protein, produced by the cells that line the blood vessel walls, interacts with blood cells called platelets to form a plug which prevents the blood from flowing at the site of injury.  People with von Willebrand Disease are unable to make this plug because they do not have enough von Willebrand Factor or their factor is abnormal. 

Researchers have identified many variations of the disease, but most fall into the following classifications:

  • Type I: This is the most common and mildest form of von Willebrand disease. Levels of von Willebrand factor are lower than normal, and levels of factor VIII may also be reduced. 
  • Type II: In these people, the von Willebrand factor itself has an abnormality. Depending on the abnormality, they may be classified as having Type IIa or Type IIb. In Type IIa, the level of von Willebrand factor is reduced, as is the ability of platelets to clump together. In Type IIb, although the factor itself is defective, the ability of platelets to clump together is actually increased. 
  • Type III: This is severe von Willebrand disease. These people may have a total absence of von Willebrand factor, and factor VIII levels are often less than 10%. 
  • Pseudo (or platelet-type) von Willebrand disease: This disorder resembles Type IIb von Willebrand disease, but the defects appear to be in the platelets, rather than the von Willebrand factor.

Von Willebrand Disease is a genetic disease that can be inherited from either parent.  It affects males and females equally.  A man or woman with VWD has a 50% chance of passing the gene on to his or her child.  There are no racial or ethnic associations with the disorder. A family history of a bleeding disorder is the primary risk factor.

VWD subtype I and II are usually inherited in what is known as a “dominant” pattern. This means that if even one parent has the gene and passes it to a child, the child will have the disorder. 

VWD Type III von Willebrand disease, however, is usually inherited in a “recessive” pattern. This type occurs when the child inherits the gene from both parents. Even if both parents have mild or asymptomatic disease, their children are likely to be severely affected.

Diagnosis of von Willebrand Disease can be difficult.  Blood tests can be performed to determine the amount, structure and function of von Willebrand Factor.  Since levels can vary, sometimes tests may need to be repeated.  A person suspected of having von Willebrand Disease should be referred to a hematologist who specializes in the diagnosis and treatment of bleeding disorders. 

Usually, people with VWD bruise easily, have recurrent nosebleeds, or bleed after tooth extraction, tonsillectomy or other surgery. Recurrent nosebleeds are also a hallmark of VWD.  Women can have increased menstrual bleeding. 

For minor bleeds, treatment may be unnecessary.  There are a range of treatment choices that depend on whether the VWD is mild or severe.

Stimate® or desmopressin acetate (DDAVP), a nasal spray, is the treatment of choice for mild von Willebrand disease. Bleeding is usually controlled in individuals with mild von Willebrand disease by using this nasal spray to boost their own factor VIII and von Willebrand levels. DDAVP may be given to increase the amount of the von Willebrand factor long enough for surgery or dental procedures to be performed. DDAVP is a synthetic product that carries no risk of infectious disease.

For excessive bleeding, infusions of a factor VIII concentrate rich in von Willebrand factor, such as Humate-P®, Alphanate® or Koate DVI®, may be required.  Humate-P, manufactured by ZLB-Behring, is the only FDA-approved Factor VIII concentrate for use in von Willebrand Disease. 

If trauma occurs or surgery is anticipated, desmopressin acetate can be given as a means of raising the von Willebrand factor level.  

Aspirin and many of the drugs used for pain can aggravate bleeding because they interfere with platelet function. People who have von Willebrand disease can take acetaminophen for pain relief because it does not inhibit platelet function.

The National Hemophilia Foundation’s Medical and Scientific Advisory Council (MASAC) issued a treatment recommendation for von Willebrand disease in 1999.  To receive a copy of this recommendation, call 1-800-42HANDI.