Wisconsin Bleeding Disorders Network

Wisconsin's Best Connection to the Bleeding Disorders Community

Hemophilia

  • Refers to  a group of inherited disorders that cause abnormal bleeding. The bleeding occurs because part of the blood — called plasma — has too little of a protein that helps blood clot.
  • Symptoms of hemophilia range from increased bleeding after trauma, injury, or surgery to sudden bleeding with no apparent cause.

There are two types of Hemophilia:

Hemophilia A results from too little of a plasma protein called factor VIII, which helps blood clot. The greater the deficiency, the more severe the symptoms.

  • Mild hemophilia: 5% to 25% of the normal factor VIII level
  • Moderate hemophilia: 1% to 5% of the normal factor VIII level
  • Severe hemophilia: Less than 1% of the normal factor VIII level
  • Most people who have hemophilia A have moderate or severe symptoms.
  • Hemophilia B results from too little of a plasma protein called factor IX, which helps blood clot. As in hemophilia A, hemophilia B can be mild, moderate, or severe. The greater the deficiency, the more severe the symptoms. 
If there is no family history of hemophilia, an infant would not be tested for the condition. However, if there is a family history of hemophilia, specific tests can be done from an umbilical cord blood sample to see if a newborn infant has hemophilia. In fact, if the family desires, such testing can be done before a child is born.

With moderate or severe hemophilia, doctors and caregivers usually don't see any signs of the condition at birth or even for some time afterward. Symptoms in children may include the following:

  • Heavy bleeding in a male baby after circumcision
  • Excessive bruising or unusual bleeding during teething
  • Swollen, bruised joints or muscles when learning to walk
  • Frequent falls and bumps

With mild hemophilia, you may not have any noticeable symptoms until you undergo a dental procedure, which may cause you to bleed heavily, or you may not have any unusual bleeding unless you are injured in an accident or have surgery.


  • Problems Caused by Hemophilia

Internal bleeding resulting from hemophilia may lead to several health problems, including the following:

  • Joint deformity
  • Bleeding in the kidneys
  • Bleeding in the throat, leading to difficulty breathing
  • Bleeding in the brain, leading to brain damage

Joint deformity can be a severe, disabling consequence of hemophilia if joint bleeds are not promptly and adequately treated. People with severe hemophilia may suffer spontaneous bleeding in the joints. Those who have less severe hemophilia may have bleeding in their joints as the result of falls or other injuries. Bleeding in a joint can cause scarring in the joint. With repeated bleeds, the joint may lose mobility and becomes susceptible to further bleeding. The knee, ankle and elbow joints are most commonly affected. Bleeding into the muscles of the legs can also be severely disabling.

Blood in the urine may occur on occasion, due to bleeding within the kidneys.

Bleeding into the throat, if not promptly treated, can interfere with breathing so much that a patient may need to be put onto a ventilator until the bleeding stops and swelling goes down.

Bleeding into the brain may cause permanent brain damage and disability or even death. While usually caused by trauma, in very severe cases of hemophilia, these areas may bleed without known injury.

What Causes Hemophilia?

Hemophilia is a genetic disease linked to a defective gene on the X chromosome. Chromosomes come in pairs - women have two X chromosomes while men have one X and one Y chromosome.

A woman who has the defective gene is called a "carrier" -- she carries the disease and can pass it to her children. In most cases, though, the woman has no symptoms of hemophilia. When a woman who is a carrier has a son, the son receives one X chromosome from his mother, so he has a 50% chance of receiving the defective gene (and a 50% chance of receiving a normal copy of the gene). Boys who receive the defective gene have hemophilia. Likewise, when a woman who is a carrier has a daughter, the daughter has a 50 percent chance of receiving the defective gene and, thus, being a carrier herself.

Men who have hemophilia do not pass the disease to their sons because boys inherit only a Y chromosome from their father. However, men do pass their X chromosome, and thus a defective gene, to each of their daughters, so each of their daughters is a carrier.

If the father has hemophilia and the mother is a carrier, there is a chance the daughter will have hemophilia.

About 70% of people who have hemophilia can trace hemophilia back through their family for multiple generations. In about 30% of newly diagnosed infants with hemophilia, no other family member is known to have had hemophilia. In these cases a mutation or change has occurred in the factor VIII or factor IX gene. From the time of the mutation, the affected person can transmit the defective gene to his or her children

SOURCES:
US Library of Medicine Genetics Home Reference.
National Heart, Lung and Blood Institute.
National Hemophilia Organization.


von Willebrand Disease (vWD)

Normally, when one of your blood vessels is injured, you start to bleed. Small blood cell fragments called platelets (PLATE-lets) clump together to plug the hole in the blood vessel and stop the bleeding. Von Willebrand factor acts like glue to help the platelets stick together and form a blood clot.

Von Willebrand factor also carries clotting factor VIII (8), another important protein that helps your blood clot. Factor VIII is the protein that's inactive or missing in people who have hemophilia, another clotting disorder.

VWD is more common and usually milder than hemophilia. In fact, VWD is the most common of all the inherited bleeding disorders. It occurs in about 1 out of every 100 to 1,000 people. VWD affects both males and females, while hemophilia mainly affects males.

Types of von Willebrand Disease
There are three major types of VWD
  • Type 1
In type 1 VWD, you have a low level of von Willebrand factor, and you may have lower than normal levels of factor VIII. This is the mildest and most common form of VWD. About 3 out of 4 people who have VWD have type 1.
  • Type 2
In type 2 VWD, the von Willebrand factor doesn't work the way it should. Type 2 is divided into subtypes: 2A, 2B, 2M, and 2N. Different gene mutations (changes) cause each type, and each is treated differently. So it's important to know the exact type of VWD that you have.
  • Type 3
In type 3 VWD, you usually have no von Willebrand factor and low levels of factor VIII. Type 3 is the most serious form of VWD, but it's very rare.Overview

Most people who have VWD have type 1, a mild form. This type usually doesn't cause life-threatening bleeding. You may need treatment only if you have surgery, tooth extraction, or trauma. If you need treatment, medicines and medical therapies are used.  Some people who have severe forms of VWD need emergency treatment to stop bleeding before it becomes life threatening.  Early diagnosis is important. With the right treatment plan, even people who have type 3 VWD can live normal, active lives.

SOURCE: 
National Heart, Lung, and Blood Institute


Rare Bleeding Disorders
Rare bleeding disorders are deficiencies in clotting factors I, II, V, VII, X, XI and XIII. In general, these rare bleeding disorders are passed down in an autosomal recessive fashion, which means they affect men and women equally. This also means that when the factor deficiency is inherited from only one parent, the child will be a carrier of the condition, though he or she will usually not have symptoms. New mutations may also appear; in these cases, the family history will be negative. In populations with a tradition for consanguinity (marriage to a blood relative), incidence and prevalence may increase significantly.

  • Factor I Deficiency
Factor I deficiency is a collective term for three rare inherited fibrinogen deficiencies: afibrinogenemia (fibrinogen absent), hypofibrinogenemia (low levels of fibrinogen) and dysfibrinogenemia (dysfunctional fibrinogen). About 1 to 2 people out of 1 million will have a FI deficiency. Factor I deficiency symptoms include:
  • Easy bruising
  • Nose and mouth bleeds
  • Soft tissue bleeds
  • Occasional thrombotic episodes
  • Recurrent miscarriages

  • Factor II Deficiency
Factor II (FII) deficiency Congenital prothrombin (FII) deficiency is very rare and estimated at 1:2,000,000 individuals. It may be quantitative (type 1 prothrombin deficiency) or qualitative (dysprothrombinemia). Both forms are usually symptomatic at levels below 25% of normal FII activity.

  • Factor V Deficiency
Factor V (FV) deficiency FV deficiency is a rare, inherited bleeding disorder with an incidence of 1 in 1 million and a symptomatology ranging from mild to severe. More than 15 mutations are known to cause this condition, and approximately 200 cases of mutations have been described so far.

  • Factor VII Deficiency
It is estimated that FVII deficiency occurs in 1 in 500,000 people. FVII deficiency is usually severe. Patients with less than 1% FVII activity may experience symptoms similar to hemophilia. FVII deficiency presents with a wide spectrum of symptom severity that sometimes correlates poorly with FVII levels, a number of patients with undetectable FVII being totally asymptomatic.

Other factor VII deficiency symptoms include:

  • Joint bleeds
  • Spontaneous nosebleeds (epistaxis)
  • Bleeding in the stomach, intestines and urinary tract
  • Severe menorrhagia in women

  • Factor X Deficiency
The incidence of FX deficiency is estimated at 1 in 500,000 births. People with mild forms of FX deficiency usually do not have bleeding episodes but may experience bleeding after trauma or surgery. The symptoms of severe FX deficiency are similar to hemophilia; however, intracranial bleeds are seen more often in FX deficiency. In addition, women with FX deficiency may have menorrhagia or be susceptible to first-trimester miscarriage.

  • Factor XI Deficiency
Factor XI (FXI) deficiency  The incidence of FXI deficiency (sometimes called hemophilia C) is estimated at 1 in 1 million in the background population; however, the disease is much more common in Ashkenazi Jews, with a prevalence of 1:190 homozygous (carrying two defect genes). Patients with FXI deficiency rarely have spontaneous bleeds but may need treatment for surgery. There is a poor relationship between factor levels and bleeding tendency.

Factor XI deficiency symptoms may include:

  • Bruising
  • Nosebleeds (epistaxis)
  • Blood in the urine
  • Hemorrhage after trauma or surgery
  • Menorrhagia and prolonged bleeding after childbirth

  • Factor XIII Deficiency

FXIII deficiency is the rarest of the factor deficiencies, affecting an estimated 1 in 5 million births. Prolonged bleeding is associated with the lack of FXIII but is usually seen only after a trauma. In addition, there is a high risk of head bleeds with or without trauma among severe patients.

Other common factor XIII deficiency symptoms include:

  • Soft tissue bleeds
  • Menorrhagia
  • Joint bleeding
  • Persistent bleeding during circumcision or at the site of the umbilical cord
  • Impaired wound healing
  • Recurrent hemoperitoneum during ovulation
  • Recurrent miscarriages

SOURCE:
http://www.allaboutbleeding.com/rare-factor-deficiencies.aspx


Platelet Disorders
Platelets are essential to primary and secondary hemostasis, including coagulation, or clot formation. When platelets do not function properly, prolonged bleeding may occur. Bleeding complications in inherited platelet disorders illustrate the importance of platelets to normal hemostasis. Causes of inherited platelet dysfunction range from defects in receptors important for platelet adhesion and aggregation (GPIb, GPIIb/IIIa) to defects in signaling molecules or transcription factors. The defect might also affect platelet activation, secretion and the secondary wave of platelet aggregation.

Platelet Disorder Symptoms

Platelet-type bleeding symptoms include mucocutaneous bleeding, such as easy bruising, petechial bleeding, epistaxis and excessive bleeding following invasive surgical and dental procedures. However, there is considerable heterogeneity in the severity of bleeding problems associated with congenital platelet disorders. Congenital platelet disorders can alter circulating platelet number, function or both. Some of the more common inherited platelet disorders include Bernard-Soulier-Syndrome, Glanzmann thrombasthenia, storage pool disorders and Wiskott-Aldrich-Syndrome. 

Symptoms of a platelet disorder include:
  •           Bruising
  •           Nosebleeds (epistaxis)
  •           Mucocutaneous and other petechial bleeding
  •           Menorrhagia
  •          Bleeding after surgical and dental procedures such as tonsillectomy, adenoidectomy, tooth extraction and childbirth.