What is it?

A bleeding disorder is an acquired or inherited tendency to bleed excessively. Normally, blood remains in the circulatory system inside the blood vessels. However, if veins or arteries are injured, they will begin to leak blood, either externally or into body tissues. The body stops the blood loss through a complex clotting process called haemostasis. During haemostasis, the injured blood vessel constricts to reduce blood flow, platelets adhere to the injury site and clump together to form a loose platelet plug, and a process of clot formation called the coagulation cascade is initiated.

The coagulation cascade has two branches: if the damage is to tissue, the body responds by activating the extrinsic pathway. If the injury is to a blood vessel wall, the intrinsic pathway is activated. Each of these pathways utilises different coagulation factors, proteins that are carried in an inactive form in the blood. These factors are sequentially activated down one pathway or the other and come together to complete the clotting process in the common pathway. By the end of the cascade, insoluble fibrin threads have been formed, woven through the platelet plug, crosslinked to make a fibrin net and stabilised at the injury site. The resulting stable blood clot creates a barrier that prevents additional blood loss and remains in place until the area has healed. When the clot is no longer needed, other factors are activated to dissolve and remove it.

Bleeding disorders occur when something goes wrong with the clotting process. If a component is missing, deficient, or dysfunctional, excessive bleeding may occur. Such bleeding may be severe, with bleeding episodes beginning in early childhood, or mild – involving bleeding for an extended period of time following a surgery, dental procedure or trauma. Bleeding disorders may cause symptoms that range from nosebleeds, bleeding gums, bruising, heavy menstrual periods, and blood in the stool and urine to arthritis type symptoms (damage from bleeding into joints), loss of vision, and chronic anaemia.

Abnormalities may involve: the structure of the blood vessels, the production or function of one or more of the coagulation factors, the development of antibodies against one or more of the factors, the production or function of the platelets, and/or the integrity and stability of the blood clot. Inherited bleeding disorders are rare and tend to be caused by a deficiency or dysfunction in a single coagulation factor or clotting component.

The most common are Haemophilia A (factor VIII deficiency) and von Willebrand’s disease (von Willebrand factor is a protein that helps platelets adhere to the injury site). Acquired bleeding disorders are varied and occur more frequently than inherited disorders. Common ones include multiple factor deficiencies caused by liver disease or vitamin K deficiency (since many coagulation factors are produced in the liver and several are vitamin K dependent) and factor inhibitors (especially factor VIII inhibitor – an antibody against factor VIII).

Structural problems

Inherited
Haemorrhagic Telangiectasia — blood vessels are more fragile than usual leading to recurrent bleeding episodes

Ehlers-Danlos syndrome — collagen that supports blood vessels is unusually weak and elastic, making blood vessels less protected and more prone to injury

Acquired
Allergic purpura — small blood vessels are inflamed and prone to leakage, a condition thought to be an autoimmune response and that may be acute or chronic

Platelet deficiency

Also known as thrombocytopenia.

Inherited
A variety of other rare inherited conditions may cause platelet disorders

Acquired

• Bone marrow not making enough — bone marrow failure
• Idiopathic thrombocytopenic purpura (ITP), decreased platelets, cause unknown, thought to have autoimmune cause. May go away on its own in children but adults usually require treatment with suppression of the immune system. 
• Drugs such as heparin, quinine, sulfa antibiotics, and gold salts may decrease number of platelets
• Drugs such as aspirin and nonsteroidal anti-inflammatory drugs may cause dysfunctional platelets
• Disease related: HIV, liver disease, kidney failure, leukaemia, multiple myeloma, cirrhosis of the liver, and systemic lupus erythematosus may all cause decreased platelet counts
• Massive blood replacement (platelets don’t last in stored blood)
• Cardiopulmonary bypass surgery (platelets are activated and become deficient and dysfunctional)

Coagulation factor deficiency

Inherited

Haemophilia A (factor VIII deficiency) — X-chromosome linked bleeding disorder that occurs primarily in males. The first bleeding episode may be with circumcision or other procedure as an infant. The severity of the bleeding caused by a factor VIII deficiency depends on its activity level (how well it is functioning). If it is very low it may cause severe life threatening bleeding, if it is moderate it may only cause mild to moderate bleeding – becoming an issue primarily when having surgery or dental procedures.

von Willebrand’s disease — the commonest bleeding disorder, resulting from reduced (type 1) or dysfunctional (type 2) or absent (type 3) von Willebrand factor. von Willebrand factor is a protein that adheres platelets to the site of a blood vessel injury. It is associated with factor VIII: if VIII is deficient then vWF may be affected.

Other factor deficiencies — II, V, VII, IX, X, (Haemophilia B, also called Christmas disease), all much less common.

Acquired

• Liver dysfunction or disease (because the liver synthesises factors II, VII, IX and X)
• Vitamin K deficiency
• Fat malabsorption
• Snake venom (produces intravascular activation of clotting with consequent consumption of clotting factors)
• Therapy for bone marrow and myeloproliferative disorders
• Factor inhibitors (antibodies that target a specific clotting factor, such as factor VIII, decreasing its level and making factor replacement more of a challenge)
• Anticoagulant drugs: such as coumadin (warfarin) or heparin, these drugs are used to treat clotting disorders but in excessive amounts may cause bleeding
• Some bacterial infections
• DIC (disseminated intravascular coagulation), may cause both bleeding and clotting. It is usually an acute condition, for example from a complicated childbirth – as a result of uterine tissue contacting the blood stream, from an endotoxin produced during a severe infection, or due to certain cancers such as leukaemia. DIC causes tiny clot formation throughout the body, using up clotting factors at an accelerated rate – leading to excessive bleeding.

Tests

Bleeding disorder testing is a step-by-step investigative procedure. You usually cannot tell the cause of the bleeding by its location, timing or severity. To evaluate a bleeding tendency useful tests are a PT (prothrombin time – evaluates the extrinsic and common pathways), APTT (activated partial thromboplastin time – evaluates the intrinsic and common pathways), full blood count (FBC) first to see whether or not the patient is anaemic, and to measure the platelet count.  If the APTT is prolonged, then follow-up is done with other testing to look for specific factor deficiencies and to see whether or not there may be factor inhibitors.

Some of the tests that may be ordered include:

Treatment

There is no cure for most bleeding disorders. Typically, they are identified, monitored and controlled both to prevent excessive blood loss and to prevent complications that may arise. Bleeding disorder treatment is centred around avoidance, replacement and prevention. The degree and frequency of treatment needed will depend on the severity of the deficiency or condition, whether or not there is a stimulus for bleeding – such as surgery or trauma, and whether or not the condition progresses or worsens over time.

Simply avoiding injury, limiting physical contact sports for instance, and setting up the daily environment to avoid cuts, bruises and trauma may be enough to minimise bleeding episodes in those with mild conditions, and under most circumstances, in those with moderate bleeding tendencies. Someone with severe deficiencies, such as Haemophilia A (factor VIII), and/or someone who is having an acute bleeding episode will need to have one or more of their coagulation factors replaced. Factor VIII and a few other individual factors are available in a concentrated form that is expensive but effective. Single and multiple factor deficiencies can also be treated with transfusions of fresh frozen plasma or plasma concentrates that contain all of the coagulation factors. These concentrates and replacements can be given during a bleeding episode and as a preventative measure before necessary surgeries and dental procedures to control excessive bleeding.

If the bleeding disorder is due to dysfunctional or deficient platelets, they may also be transfused. If the disorder is due to von Willebrand’s disease a drug called desmopressin (DDAVP) may be given to improve clotting temporarily. It causes the release of factor VIII and vWF, from stores in the blood vessel walls and may temporarily raise levels high enough and long enough to allow procedures to be performed without transfusions.

If a bleeding disorder is due to an acquired condition, it may improve or worsen as the underlying condition is resolved or progresses. If, for instance, factor deficiencies are due to a lack of vitamin K, seen for example in warfarin overdose, they willreturn to normal with vitamin K supplementation. If they are due to liver disease or to a cancer, they will likely follow the course of the disease. If a bleeding disorder is due to or exacerbated by the development of factor antibodies, such as antibodies to factors VIII or IX, increased amounts of factor replacements may need to be given, different types or replacements may need to be used, and/or patients may need to take corticosteroids or other immune-suppressive drugs to reduce their antibody levels.

With an acute condition such as DIC (disseminated intravascular coagulation), immediate treatment may be crucial and complicated. Since DIC involves both clotting and bleeding throughout the body, treatment may involve platelet and clotting factor transfusions but the underlying principle is to treat the cause.