Bleeding Disorders

Von Willebrand disease is also a genetic bleeding disorder that prevents the blood from clotting normally. It is caused by a deficient or defective blood protein known as von Willebrand factor. Although less widely known than hemophilia, von Willebrand disease (vWD) is estimated to affect over two million people in the U.S., and as many as 1 in 100 people. VWD is a milder disorder with fewer and less severe symptoms, although a severe form can occur. Of the three main types, type 1 (the mildest form of the disease) accounts for 70% of cases. Both males and females can have von Willebrand disease. Symptoms include frequent nosebleeds, a tendency to bruise easily, and excessive bleeding following surgery. With severe vWD, joint bleeding much like hemophilia can occur.

Rare bleeding disorders are deficiencies in clotting factor 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.

Factor Deficiencies

Factor I: Factor I deficiency is a collective term for three rare inherited fibrinogen deficiencies. It very rare, occurring in 1-2 people per million.

 – Afibrinogenemia: No fibrinogen is present in the body.

 – Hypofibrinogenemia: Some fibrinogen with normal structure is present but below levels needed for normal clotting.

– Dysfibrinogenemia: Normal amounts of fibrinogen are manufactured by the liver, but they don’t clot properly.

Factor II: Factor II deficiency is also prothrombin deficiency. Prothrombin a precursor to thrombin, an enzyme that converts fibrinogen into fibrin to strengthen a clot. There are two types, Dysprothrombinemia results when there is an abnormality in the structure of prothrombin and Hypoprothrombinemia occurs when the body doesn’t produce enough prothrombin. It is very rare occurring in 1-2 people per million.

Factor V: The Factor V protein, also known as Labile Factor and Proaccelerin, is a catalyst accelerating the process by which prothrombin is converted to thrombin, the initial step in clot formation. Factor V deficiency also called Owren’s disease or parahemophilia, is usually inherited in an autosomal recessive fashion, meaning both parents must carry the gene to pass it on to their children. Its incidence is about 1 in 1 million; with fewer than 200 cases being documented worldwide.

Factor VII: Factor VII is a protein that, when bound to tissue factor, initiates the clotting cascade, which leads to the formation of a blood clot. It is considered the most common of rare bleeding disorders, its incidence is estimated at 1 per 300,000-500,000

Factor X: Factor X is also know as Stuart-Prower factor. Factor X protein plays an important role in activating the enzymes that help to form a clot. It needs vitamin K for synthesis, which is produced by the liver. It is estimated to effect 1 in 500,000 to 1 in a million people.

Factor XI: Factor XI deficiency is also called hemophilia C, plasma thromboplastin antecedent deficiency, and Rosenthal syndrome. Factor XI plays an important role in the clotting cascade, which leads to a clot. It helps generate more thrombin, a protein that converts fibrinogen to fibrin, which traps platelets and helps hold a clot in place. Its incidence is estimated at 1 in 100,000 in the general population but in Israel or other large Ashkenazi Jewish communities it occurs up to 8% because of intermarriage.

Factor XII: Factor XII deficiency is also called Hageman factor deficiency. Factor XII interacts with the activation of FXI to FXIa to generate thrombin, a protein that converts fibrinogen to fibrin, which traps platelets and helps hold a clot in place. Its incidence is estimated at 1 in a million people and is more common in Asians than other ethnic groups.

Factor XIII: Factor XIII protein stabilizes the formation of a blood clot. Without it, a clot will still develop, but will then break down and cause recurrent bleeds. It is the rarest factor deficiency, occurring in 1 per 5 million births.

Rare platelet disorders may be inherited or acquired after birth. These disorders can last a short time or be a chronic condition. On the positive side, platelet disorders are usually milder than the other types of bleeding disorders. There’s much we don’t know about platelet disorders. In some cases, patients may only know they have an “unspecified” platelet disorder.

Platelets are tiny, irregularly shaped blood cell pieces (called fragments) that play an important role in clotting blood. When an injury occurs and a blood clot is needed, the platelets become sticky and help plug the site of the injury. They attract other proteins needed in the clotting process and they help form a stable clot. There are several ways or reasons that platelets may not work properly.

Bernard-Soulier Syndrome: Individuals with Bernard-Soulier Syndrome have very large platelets, larger than red or white blood cells, and are missing the protein Lycoprotein lb that helps them stick together to form a clot. Symptoms can vary from mild to severe. Bernard-Soulier syndrome affects approximately 1 in one million people.

Glanzmanna Thrombasthenia: occurs when a protein that helps platelets work properly is defective. Numerous proteins help platelet work properly. One of those is glycoprotein. These proteins work together like a bridge to connect platelets with each other. When they are defective or missing, platelets cannot form a plug to stop the bleeding. Glanzmann Thrombasthenia is inherited from both parents and can occur in both men and women. It is not well known how often Glanzmann Thrombasthenia occurs. Symptoms can include excessive bleeding after surgery or injury, easy bruising, swelling, painful joints, and in women, heavy menstruation.

Gray Platelet Syndrome (GPS): is a rare inherited bleeding disorder which results from the absence or reduction of alpha-granules in platelets which store proteins that promote platelet adhesiveness and wound healing when secreted during an injury. About 60 cases from various populations around the world have been described in literature to date. GPS is caused by a gene mutation and inherited in an autosomal recessive manner. Signs and symptoms usually appear at birth or in early childhood and include low platelet counts, easy bruising, prolonged bleeding, and nose bleeds.

Platelet Storage Pool Disease: are a number of rare disorders that occur when a person’s platelet granules — part of the platelet that are involved in the clotting process — don’t work at they should. These disorders are known as platelet storage pool diseases.  Lab tests are needed to diagnose SPDs.

Delta Storage Pool Deficiency: is a mild to moderate bleeding disorder in which the primary defect is a deficiency of dense or delta granules and the chemicals normally stored inside them. Without these chemicals, platelets are not activated properly and the injured blood vessel does not constrict to help stop bleeding.

Immune Thrombocytopenic Purpura (ITP): is a disorder characterized by a decrease in the number of platelets in the blood. It is caused by an immune reaction against one’s own platelets.

Qualitative Platelet Disorder (QPD): is a disorder effecting the structure or function of platelets. People with this disorder will have an adequate number of platelets but poor “quality” of clotting.

Hypodysfibrinogenemia: is a rare hereditary fibrinogen disorder cause by mutations in one or more of the genes that encode a factor critical for blood clotting, fibrinogen. These mutations result in the production and circulation at reduced levels of fibrinogen at least some of which is dysfunctional.

Additional Bleeding Disorder Information can be found HERE.