Haemophilia is a hereditary bleeding disorder that affects males. Approximately 1 in 5,000 males is born with haemophilia. An estimated 400,000 males have haemophilia A or B. According to the World Federation for Hemophilia, only 25% have confirmed diagnosis and access to adequate care. An estimated 75% of people with haemophilia live in the developing world.
Patients with haemophilia A have either decreased, defective or absent production of the blood clotting protein, factor VIII. Those with haemophilia B have similar deficiencies with clotting factor IX. For people with haemophilia, bleeds often occur in the joints, particularly knees and ankles. Bleeds can also occur in the muscles, soft tissues, gastrointestinal tract or even the brain. Trauma, major surgery, tooth extractions or other minor surgical interventions require medical intervention to manage the associated bleeding. Without treatment bleeds are painful and can cause lasting damages and lead to impaired mobility.
Haemophilia is characterised as "severe" when the activity
of the affected clotting factor (FVIII or FIX) is less than 1% of
normal. Severe Haemophilia is often associated with spontaneous
bleeding, i.e. not caused by injury. Haemophilia is termed
"mild" when the relevant clotting factor activity is greater
than 5%, but less than normal and "moderate" when clotting
factor activity is between 1% and 5% of normal. Approximately 50% of
haemophilia patients have severe disease and can require treatment for
bleeding several times per month.
Acquired haemophilia is a spontaneous development of inhibitors to one’s own FVIII. Acquired haemophilia occurs in about one person per million. The underlying cause of inhibitor development is usually idiopathic (unknown) but may occur in relation to pregnancy, autoimmune disease, the use of certain medications or cancer. Patients with acquired haemophilia may present to the hospital as a result of a severe spontaneous bleeding episode. These bleeding episodes are very difficult to control, and will not typically respond to treatment with FVIII.
Haemophilia A and B can be treated by substituting the missing clotting factor by intravenous injection, either when bleeding occurs or prophylactic. The replacement clotting factors have typically been obtained from human plasma or, more recently, from recombinant technology.
Treatment of haemophilia A and B patients is normally based on
replacement therapy, i.e. substitution of the missing clotting factor.
The replacement clotting factors are typically obtained from human
plasma or, more recently, from recombinant, i.e. genetically
One of the most feared complications of the treatment of haemophilia
is the development of ‘inhibitors’. ‘Inhibitors’ are antibodies to
FVIII or FIX that can develop in patients with haemophilia following
replacement therapy with the missing coagulation factor. The incidence
of inhibitors complicating treatment of haemophilia A and B is
approximately 30% in haemophilia A and 3 to 5% in haemophilia B
patients. Most of these antibodies develop during childhood. The
management of haemophilia patients with inhibitors is difficult.
Clinically, most inhibitors are detected when patients fail to respond
to standard replacement therapy. Inhibitor levels are measured in
Bethesda units (BU).
von Willebrand Disease
Although more common than haemophilia, von Willebrand Disease (vWD)
is often less serious. Many people with vWD have very mild symptoms.
Often the first clues come during surgery or after a serious injury,
when bleeding will not stop. Women with vWD tend to have more symptoms
than men because of menstruation and childbirth. VWD is most often
caused by genetic mutations that either impair the ability to make von
Willebrand factor or lead to the production of defective forms of the
Allied rare bleeding disorders
Among inherited bleeding disorders, haemophilia A and B along with
von Willebrand Disease, represent 95–97% of bleeding disorders.
Deficiency of the remaining coagulation factors like fibrinogen,
factor II, V,V+VIII, VII, X, XI and XIII are classified as Rare
Bleeding Disorders (RBDs).They affect one person out of 500,000–2
million, depending on the deficient factor and are inherited in an
autosomal recessive fashion. Both men and women can be similarly
affected by RBDs because the deficiency is not linked to the X
The most common symptoms reported in all the deficiencies of any severity are mucocutaneous bleeding, e.g. nose bleeding, mouth and gums bleeding, presence of blood in urine, bruises, and bleeding during or after surgery. Excessive bleeding during the menstrual period and spontaneous abortion is often found in women with deficiency of any coagulation factor, regardless of severity.