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What is a Bleeding Disorder?

Bleeding disorders are a group of disorders that share the inability to form a proper blood clot. They are characterized by extended bleeding after injury, surgery, trauma or menstruation. Sometimes the bleeding is spontaneous, without a known or identifiable cause. Improper clotting can be caused by defects in blood components such as platelets and/or clotting proteins, also called clotting factors.

The body produces 13 clotting factors. If any of them are defective or deficient, blood clotting is affected; a mild, moderate or severe bleeding disorder can result.

Resource: National Hemophilia Foundation

Hemophilia and von Willebrand Disease

Hemophilia and von Willebrand disease (vWD) are the most common inherited bleeding disorders. They are caused by a lack of a specific clotting factors needed to control bleeding. Hemophilia is an inherited X-linked genetic condition that primarily affects males. Von Willebrand disease is a genetic disorder affecting both men and women, caused by a genetic change on the twelfth chromosome.

2021 WFH Guidlines on the Management for VWD

2021 WFH Guidlines for Diagnosis of VWD

VWD Guidelines Management Snapshot – English

VWD Guidelines Management Snapshot – Spanish

VWD Guidelines Diagnosis Snapshot – English

 VWD Guidelines Diagnosis Snapshot – Spanish

Hemophilia Presentation


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Von Willebrands Disease video from NHF


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Bleeding Disorders

Hemophilia
Hemophilia is a genetic bleeding disorder that prevents the blood from clotting normally. Certain bleeding episodes, such as brain bleeding, may be life threatening. Hemophilia occurs primarily in males; however, a female may, on occasion, be affected. Woman who are carriers of hemophilia may have low factor VIII or IX activity, may be symptomatic and may be considered to have Hemophilia. They can often require the same factor replacement as males during trauma, surgery and child birth. All carriers of hemophilia should be tested before surgery and other medical procedures.

The two types of hemophilia are factor VIII deficiency, also known as hemophilia A, and factor IX deficiency (hemophilia B), or Christmas disease. The main symptom of hemophilia is uncontrolled bleeding, characteristically into muscles and joints. Repeated bleeding results in pain, swelling and, if left undertreated or untreated, causes permanent damage. There are three levels of severity: mild, moderate and severe. Individuals with mild hemophilia have prolonged bleeding usually only with surgery, tooth extraction, or major injuries. Individuals with moderate hemophilia may have internal bleeding into joints or muscles following relatively minor trauma, such as a sprain or hard fall. In severe hemophilia, bleeding episodes are more frequent. They can occur with no apparent injury or cause, in addition to prolonged bleeding with trauma and surgery. Bleeding can be as common as two or three times weekly for those severely affected and not on prophylactic therapy treatment. Frequent episodes are both painful and expensive.

While hemophilia is most commonly genetically inherited, approximately one third of all newly diagnosed cases occur in families with no prior history. Instead, the disorder results from a spontaneous genetic mutation. Hemophilia A, which accounts for 80% of all hemophilia patients, occurs in approximately 1 in 5,000 male births. Hemophilia B, accounts for 20% of all case and occurs in 1 out of every 10,000 male births. There are approximately 17,000 people with hemophilia in the United States. Of these, approximately 65% are classified as severe, 15% moderate, and 25% mild, depending upon the level of clotting factor (protein) found in their blood. The worldwide incidence of hemophilia is estimated at more than 400,000 people. Approximately 70% of people around the world do not have access to treatment. While treatment exists; it is costly and may require lifelong infusions of replacement clotting factor. Hemophilia is treated with blood and/or genetically engineered replacement therapies and can have an estimated cost for treatment at $300,000.00 yearly. Currently, there is no cure.

Von Willebrand Disease

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.

In women, the disease may also cause heavy, prolonged bleeding during menstruation and excessive bleeding following childbirth. It is often undiagnosed or incorrectly attributed to a gynecologic condition. Testing is extremely complicated for a correct diagnosis, which will often lead to a missed diagnosis. Surveys conducted by the Center for Disease Control have shown that on an average, it takes 16 years for a woman with a bleeding disorder to be diagnosed from the onset of symptoms.

VWD Guidelines

New VWD Guidelines for the diagnosis and management of von Willebrand disease were released in January of 2021. These guidelines are the result of a collaborative effort between the American Society of Hematology (ASH), the International Society on Thrombosis and Hemostatsis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation for Hemophilia (WFH). The following one-page snapshots offer a summary of these guidelines and will provide you with the most important and up-to-date information. Click here to read the updated guidelines in full.

VWD Guidelines Management Snapshot – English

VWD Guidelines Management Snapshot – Spanish

VWD Guidelines Diagnosis Snapshot – English

VWD Guidelines Diagnosis Snapshot – Spanish

2021 WFH VWD Diagnosis Guidlines

2021 WFH Management of VWD Guidlines

 

Rare Bleeding Disorders

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.

 

Platelet Disorders

Our blood contains small, sticky cells called platelets. Platelets stick to blood vessels and try to block the bleeding upon an injury. They also send out a chemical signal that attracts other platelets. Those platelets stick to the platelets at the injury site to form a plug that stops the bleeding. Platelets sometimes do not work as they should and when that happens, a person has a platelet disorder.

Platelet Disorders

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.

 

Women with Bleeding Disorders

Women with Bleeding Disorders

Women also have bleeding disorders like males. However, many healthcare providers are not aware of the prevalence of bleeding disorders in females. Women can be affected by several different bleeding disorders such a von Willebrand Disease (vWD); platelet defects; Hemophilia A,B,C; and other more rare clotting disorders, as well as disorders involving the fibrinolytic system. The prevalence of bleeding disorders in females is unknown.

Although rare, cases of severe Hemophilia A and B are found in women. Either the women inherited a hemophilia gene from both her mother who is a carrier and her father who has hemophilia, or she is a genotypic carrier who has experienced extreme lyonization of the hemophilia gene, causing the women’s normal gene for the production of Factor VIII or IX to be “turned off”. Women who have moderate to severe hemophilia will have the same bleeding symptoms as males with the added features of gynecological and obstetrics complications.

References:

HNF Nurses Guide Chapter 3: Women with Bleeding Disorders

Read information about women and bleeding disorders in the November 2016 Issue of PEN.

HFA – Women Bleed Too! Toolkit

For additional information on women with bleeding disorders:
Foundation for Women & Girls with Blood Disorders

Victory for Women with Blood Disorders

Blood Sisterhood – Hemophilia Federation of America