South African Haemophilia Foundation (SAHF) Medical and Scientific Advisory Council (MASAC) Treatment Guidelines - Treatment of Bleeding Episodes

Other Bleeding Conditions

The bleeding disorder now called Haemophilia A or factor VIII deficiency has been known since biblical times. Physicians referred to it in medical literature in 1793. Haemophilia B or factor IX deficiency, on the other hand, was not recognized as a distinct entity until 1952. It is now known account for 20% of all cases of Haemophilia.

At least eight other coagulation disorders have been identified, most of them in the 20th century and some only within the past 25 years

Factor I Deficiency (Fibrinogen)

Included under this heading are several rare coagulation disorders known as congenital fibrinogen defects. They include afibrinogenemia and hypofibrinogenemia, and dysfibrinogenemia. The first two are called quantitative abnormalities because they have to do with an absent or low quantity of fibrinogen. The third is called a qualitative abnormality because the fibrinogen does not work well.

Fibrinogen, also known as Factor I, is needed for most types of platelet aggregation. People who have a Factor I deficiency have a combined bleeding disorder, meaning that both platelets and clotting are abnormal. Afibrinogenemia is the complete absence of fibrinogen. Hypofibrinogenemia is a low level of fibrinogen – less than 100mg in 1dL of blood. Both conditions are inherited in an autosomal fashion and can affect males and females.

The severity of the disorder is related to the amount of fibrinogen. Afibrinogenemia is usually discovered in newborns and can cause bleeding from the umbilical cord, genitourinary tract, or central nervous system. People with hypofibrinogenemia may have little, moderate, or severe bleeding.

Dysfibrinogenemias are due to variations in the Factor I molecule. More than 70 different types of dysfibrinogenemia have been identified. Few people who have any of these disorders suffer symptoms, although some are predisposed to form blood clots (thrombosis).

Many people with hypofibrinogenemia or dysfibrinogenemia need no treatment. Those who require treatment may be given cryoprecipitate or fresh frozen plasma. Anticoagulants are sometimes prescribed to reduce the risk of thrombosis.

Factor II Deficiency (Prothrombin)

Only 30 cases of this hereditary clotting factor defect have been identified in the whole world. It may take the form of a deficiency of prothrombin or an abnormal Factor II molecule. Either form may lead to severe bruising, excessive menstrual bleeding, postoperative hemorrhage, and occasionally muscle hematomas.

Mild cases may be treated with plasma infusion. Severe Factor II deficiencies may be treated with prothrombin complex concentrates (PCCs).

Factor V Deficiency (Proaccelerin)

Factor V deficiency is also known as Owren’s disease or parahaemophilia. This deficit was identified in Norway in 1943. Since then about 150 cases have been reported, occurring in both men and women.

The role of Factor V is to accelerate the activity of thrombin. When levels of Factor V are low, clotting is delayed or progresses slowly. People with this deficiency may have occasional nosebleeds, excessive menstrual bleeding, and bruising, although many have no symptoms. The first sign of this condition may be bleeding following surgery. The treatment is administration of fresh frozen plasma is not given because Factor V deteriorates rapidly.

Factor V deficiency has to be distinguished from a combined deficiency of Factors V and VIII, which is entirely separate disorder.

Factor VII Deficiency (Proconvertin)

This disorder is rare, occurring in one in 500,000 males and females. Diagnosis is made by testing for Factor VII in the blood. Congenital Factor VII deficiency should be distinguished from acquired Factor VII deficiency that may result from liver disease, vitamin K deficiency, or other malabsorption conditions.

When levels of the factor are less than 1% of normal, bleeding can be severe. The trauma of birth may cause bleeding in the head of a newborn. Circumcision may cause heavy bleeding. Children and adults may suffer bleeding from nose, gums, or gastrointestinal tract, and women may suffer excessive menstrual bleeding.

Severe bleeding may be treated with fresh frozen plasma or PCCs. Because the half-life of infused Factor VII is very short, patients may require treatment every 4 or 6 hours for severe bleeding or surgery.

Factor X Deficiency

Factor X deficiency ranks with Factor II as one of the rarest inherited clotting disorders, with only about 50 reported cases. Some cases are due to reduced or absent synthesis of the molecule; in other cases, the number of molecules is normal, but they don’t work properly. Several genetic variations of Factor X deficiency of varying severity have been described.

People with factor activity that is less than 1% of normal are susceptible to severe bleeding; those with 10% or more are only mildly affected. Symptoms include frequent bruising, gastrointestinal bleeding, and nosebleeds. Muscle and intracranial bleeding may be severe. Women with Factor X deficiency may have excessive menstrual bleeding and are susceptible to first-trimester miscarriage. Bleeding episodes are usually managed by infusion of fresh frozen plasma or PCCs.

Factor XI Deficiency

This hereditary disorder occurs primarily in Jews of eastern European ancestry, resumably because intermarriage within this closed group, generation after generation, allowed the defective gene to surface more frequently. In the United States, for example, most cases are found in New York and Los Angeles. Approximately 200 cases of Factor XI deficiency have been reported since it was identified in 1953.

Most patients with Factor XI deficiency have little or no bleeding. Often there is no correlation between bleeding episodes and the level of factor.

If you have factor XI deficiency, chances are your symptoms are milder than those of either haemophilia A or haemophilia B and there may be no strong relationship between your factor XI levels and bleeding complications. You may be prone to bruising, nose-bleeds, or blood in your urine. Prolonged bleeding after childbirth can occur. But you are not likely to bleed spontaneously, and haemorrhage is usually a problem only after an injury or surgery. Joint bleeds are uncommon, but delayed bleeding (starting an unexpectedly long time after an injury) may be a problem.

Factor XIII Deficiency

A hallmark of this rare inherited deficiency is poor wound healing and abnormal scar formation. The reason is that Factor XIII – fibrin stabilisation factor – is necessary for clot formation and wound healing.

The most common clinical symptom, seen in over 80% of cases, is bleeding from umbilical stump after birth. Bleeding episodes are usually lifelong and include severe bruising, hematomas, and prolonged bleeding after trauma. Characteristically, bleeding is delayed for several hours or days after trauma. Haemorrhage into the brain or spinal cord area is more common than in other inherited coagulation disorders and can be life-threatening. Plasma replacement is given to pregnant women to prevent spontaneous abortions.

Deficiency of Factor XIII can be corrected with infusions of fresh frozen plasma or factor XIII concentrates. Because of the high incidence of intracranial bleeding and spontaneous abortions, prophylaxis is often recommended.

Glossary of Coagulation Terms

Antifibrinolytic Inhibiting the breakdown of fibrin, the blood component that forms the essential portion of a blood clot
Autosomal Relating to any chromosome that is not a sex chromosome
Afibrinogenemia The absence of fibrinogen from the blood
Coagulopathy A disorder that prevents normal clotting of the blood
Dysfibrinogenemiac Malfunction of fibrinogen in the blood
Fibrinogen Factor I, a protein in the blood that is converted to fibrin by the action of thrombin
Glycoprotein A protein compound that also contains carbohydrate
Hypofibrinogenemia A low or deficient level of fibrinogen in the blood
Platelet A component of blood that contributes to coagulation
Prothrombin Factor II, a protein in the blood that is converted to thrombin in the coagulation process
Thrombin An enzyme derived from prothrombin that converts fibrinogen to fibrin