Bleeding diseases or blood clotting disorders are a group of conditions that affect the body’s ability to stop blood loss. The mechanism by which blood loss is normally stopped is known as hemostasis and involves several phases. One of these phases is the blood clotting or coagulation phase.
Here a number of chemicals known as clotting factors mediate a series of reactions (coagulation cascade) to help with the formation of a blood clot. The blood clot then strengthens the already formed platelet plug. A blood clot stops further blood loss until a more permanent repair mechanism can remove the threat. With blood clotting disorders, this mechanism of hemostasis is compromised.
What is Hemophilia?
Hemophilia is a blood clotting disease that arises due to the deficiency of one of the clotting factors. It is the most common of the bleeding/clotting disorders. About 85% of hemophilics have a deficiency of Factor VIII while the other 15% have a deficiency of Factor IX. A very rare type of hemophilia involves Factor XI.
These clotting factors play crucial roles in creating a series of chemicals known as prothrombin activator which then converts prothrombin in the blood into thrombin. This newly activated thrombin in turn converts fibrinogen in to fibrin. These long protein stands form the mesh network necessary for a blood clot.
Without fibrin, a blood clot cannot be formed at a rate that is fast enough for rapid clotting. This is a crucial phase of hemostasis and can jeopardize the life of a person especially when there is severe bleeding (hemorrhage).
Types of Hemophilia
There are two types of hemophilia :
- Hemophilia A – deficiency in Factor VII (more common)
- Hemophilia B – deficiency in Factor IX
- Hemophilia C – deficiency in Factor XI (rare)
Both these clotting factors are used in the intrinsic pathway to activate Factor X which is one of the components of prothrombin activator. The intrinsic pathway is explained in detail under blood coagulation cascade.
In this type of hemophilia, there is a deficiency in Factor VIII. This clotting factor is manufactured in the liver and the endothelial cells lining the blood vessel, circulates in the blood by binding to von Willebrand factor (vWF) and is activated by thrombin. Once activated Factor VIIIa then works with Factor IX, calcium and phospholipids to activate Factor X.
This type of hemophilia is due to a deficiency in Factor IX. It is also known as Christmas Disease. Factor IX circulates in the blood stream in an inactive form and depends on Factor XI to activate it (IXa). Once activated it works with Factor VIII, calcium and phospholipids to activate Factor X.
A third type of hemophilia known as hemophilia C is a mild form of hemophilia. It is not as common as other blood clotting disorders and is mainly seen in certain ethnic groups. This type of hemophilia is due to a deficiency of Factor XI and prevents the activation of sufficient quantities of Factor IX.
Causes of Hemophilia
Hemophlia is due to genetic abnormalities. The gene for Factor VIII (hemophilia A) is located on chromosome X and is one of the largest genes in the body. Hemophilia arises when there is a large, even complete, deletion of the gene or small mutations. The gene for Factor IX (hemophilia B) is also located on chromosome X but is not as large as the Factor VIII gene. It may also be affected by gene deletions or mutations.
Genes are the blueprint for the formation of different proteins, in this case clotting factors. These genetic abnormalities affect the liver’s ability to produce Factor VIII or Factor IX either completely or only partially. In some cases the correct amount of the protein is manufactured but it is an abnormal protein.
An important point to note with hemophilia is that due to the location of the causative clotting factors genes, on chromosome X, it is strongly associated with gender. Chromosome X, or the female chromosome, means that hemophilia is transmitted by way of the mother (carrier) and almost only affects male children because males have only one X chromosome.
Female children of a carrier are unlikely to be affected because females have two X chromosomes and one chromosome should have the appropriate “normal” gene. Nevertheless females can be affected if there is inactivation of the normal gene. This may lead to reduced levels of the clotting factor. The gene for Factor XI (hemophilia C) is on chromosome 4. This means that it can occur in both males and females.
Classification of Hemophilia
Hemophilia may be classified as severe, moderate or mild. This is based on the levels of Factor VIII or Factor IX depending on the type of hemophilia. The clinical presentation is also an indication of the severity of hemophilia.
- Clotting factor levels less than 1% (< 0.01 IU/ml)
- Spontaneous bleeding – hemarthroses (joint bleeding) and muscle hematomas
- Clotting factor levels between 1% and 5% (0.01 IU/ml to 0.05 IU/ml)
- Bleeding with mild trauma or minor surgery.
- Clotting factor levels between 5% and 40% (0.05 IU/ml to 0.4 IU/ml)
- Excessive bleeding with severe trauma or major surgery.
Signs and Symptoms of Hemophilia
In hemophilia, efficient blood clotting is compromised and even pressure or blunt force injury results in bruising. The pressure areas of the body are more often afflicted and bruising arises without any break in the skin. The blood vessels are constantly injured throughout the day even without any trauma and this leads to unexplained bruising. Even small breaks in the skin that may normally go by unnoticed leads to bleeding that can be alarming. This is often reported as unexplained bleeding. Bleeding may be profuse and prolonged with injuries, cuts and even surgical procedures including common procedures like a tooth extraction.
Joint pain and swelling may arise with bruising or bleeding into the joint space (hemarthroses). This can affect several joints simultaneously. It also leads to tightness of the joint. The more commonly affected joints are the elbows, hips, knees and ankles. Muscle hematomas are more frequently seen with severe hemophilia and more commonly seen in the calf muscles and psoas muscles.
Nosebleeds may arise spontaneously or even a minor injury to the nose or nasal cavity can lead to profuse bleeding. Blood in the urine (hematuria) or stool (hematochezia) may also be reported. Although women are rarely affected with hemophilia, in hemophilia C which can affect both sexes, there may be profuse and prolonged menses in females.
Sometimes the bleeding is not obvious. Even mild trauma can leading to bleeding in the brain or cranium (intracranial hemorrhage) or within the abdominal cavity (intra-abdominal bleeding). Hemophilics therefore need to be additionally cautious after trauma even if there is no clear indication of bleeding.
Babies born with severe hemophilia may develop cephalohematoma (bleeding under the scalp). Hemophilia may only be discovered when a male child is circumcised and there is uncontrollable bleeding.
Complications of Hemophilia
Complications are more likely to arise with severe hemophilia.
- Recurrent hemathroses (bleeding in the joint) leads to joint destruction as the joint lining thickens, the cartilage is destroyed and the bone degenerates (osteoarthrosis).
- Muscle hematomas may compress nerves as is seen with the femoral nerve due to a psoas muscle hematoma.
- Internal bleeding (hemorrhage). When there is bleeding within an compartmentalized area, it may lead to a swelling of the region with compression and destruction of the tissue. This gradually occurs without any initial signs of bruising evident on the skin surface.
- Blood-borne infections are more likely to arise in hemophiliacs receiving blood transfusions. Viral hepatitis (HBV and HCV) and HIV infection were often seen prior to stringent blood screening procedures.
- Adverse reactions to blood transfusions are more commonly seen in severe hemophiliacs with hemophilia A. Anti-Factor VIII antibodies neutralize the clotting factor and therefore activated Factor VIII (VIIIa) needs to be infused during episodes of severe bleeding.
Treatment of Hemophilia
- Desmopressin (injection or nasal spray). DDVAP is a vasopression receptor agonist that raises von Willebrand factor and this increases Factor VIII levels. This may be administered in mild to moderate hemophilia A.
- Infusions with clotting factors may be administered during episodes of bleeding in moderate to severe hemophilia A and B. Prophylactic infusions may be considered in severe hemophilia. In hemophilia C, a plasma infusion may be necessary during bleeding episodes.
Last updated on September 7, 2018.