WHAT IS VON WILLEBRAND DISEASE?  Hundreds of thousands of people in the U.S. have von Willebrand disease.  Many of these people, both men and women, are unaware and have never been diagnosed.  The information in this section is an introduction and is not presented as comprehensive information about von Willebrand disease. Blood, bleeding, clotting, and von Willebrand disease (vWd) The missing element in vWd is a protein called von Willebrand factor (vWf) The inheritance of vWd The symptoms of vWd Diagnosis of vWd Common misdiagnoses and results Testing for vWd to measure levels, function, severity, and type Test results may not be accurate Treatment for vWd Blood, bleeding, clotting, and von Willebrand disease (vWd) Blood is a fluid, carried through the body in tubes called arteries, veins, and capillaries. When a tube is injured, a small hold forms, letting blood flow out. This is called bleeding. Stopping the flow of blood from this small hole is necessary. Stopping the flow is called clotting. Blood clotting is a process that requires 3 steps to be successful. Vasoconstriction Vasoconstriction - the blood vessel narrows and slows the passage of blood from the hole Plug - platelets (tiny particles in blood) rush to the site, stick together, and act as a sticky cap or plug to stop the blood from passing out of the hole– when von Willebrand factor (vWf) is not working correctly or is missing from a persons blood, the clotting problem starts here Clot – clotting factors and proteins in the blood, stop at the site, form a solid fibrin clot, and seal the hole, stopping the flow blood – when Factor VIII/Factor IX are missing, the problem starts here - the blood vessel narrows and slows the passage of blood from the hole Bleeding stops only if all 3 steps or processes work correctly. If any of these steps is missed or does not work correctly, no clot is formed. Where clotting is unsuccessful, it is possible that the person has a bleeding disorder. In hemophilia, the commonly missing factors and proteins are Factor VIII or Factor IX. The defective or missing element in vWd is von Willebrand factor or vWf. Less frequently, a person may be missing Factors  I, II, V, VII, X, or XI. Each causes disrupted or incomplete clotting. In von Willebrand disease, the missing element is a protein called von Willebrand factor (vWf) vWf is a glue-like gel that carries and protects Factor VIII. It helps the platelets stick together, acting as a "catcher's mitt' bringing platelets to the site of the "hole" to form the platelet plug . Inability to form a platelet plug may occur after bleeding from injury, from surgery, or from no known cause. vWd occurs in 1 – 3% of the US population. vWd is an equal opportunity disorder equally affecting women and men. This means that approximately 2.6 million persons in the US have vWd. People with vWd are missing vWf causing a disruption in formation of a platelet plug and delaying clotting. A lack of vWf can also destroy Factor VIII (FVIII), since vWf is the protector of FVIII. Lack of FVIII disrupts the entire clotting chain (cascade) making clot formation slow or unlikely. Without treatment, internal bleeding can cause long-term damage, similar to the damage characteristic of hemophilia. The inheritance of vWd Unlike the chromosome for hemophilia, which is sex-linked, the transmitter for vWd is on a non-sex chromosome. This means that a child of either sex is just as likely to receive this gene. vWd is transmitted when either parent passes on an altered gene. vWd is usually dominant, meaning a parent who has vWd has a 50% chance of passing it to each child. If both parents are symptomatic for vWd, they have a 25% chance of having a severely affected child, a 50% chance of having a child who is a carrier, and 25% chance of having a child unaffected by vWd. Some cases of vWd result from a spontaneous mutation during prenatal development. These individuals will then go on to carry the disorder to future generations. In rare instances, vWD is acquired via childbirth, drug-therapy, and autoimmune diseases such as rheumatoid arthritis, types of kidney failure, or certain cancers. Levels of severity range from low to moderate to severe and will usually remain true within a family. Families have reported the existence of both vWd and hemophilia within the same family. Severe bleeding is most likely in those with severe vWd. The symptoms of vWd Recurrent nose bleeds Easy bruising Heavy or prolonged menstrual flow Bleeding from digestive or urinary tract Unusual or excessive bleeding from mouth or gums Bleeds into joints, muscles, or the brain Unusual bleeding after surgery, dental procedures, and injury Recurrent spontaneous bleeding anywhere Diagnosis of vWd Diagnosis can be at birth (in families suspecting a diagnosis). Severe bleeding can result from accident, dental work, sports injury, or trauma which may lead to diagnosis. Heavy menstrual bleeding may suggest diagnosis. Excessive bleeding from childbirth, dental work, or surgery may suggest diagnosis. Bleeding into muscles, joints, or the brain are less frequently a predictor of vWd, but in some cases, may suggest a diagnosis of vWd. Common misdiagnoses and results Medical practitioners may fail to consider a bleeding disorder as an explanation when treating a symptomatic female patient. Some may be unfamiliar with bleeding disorders, unaware of available diagnostic tests, or deem tests unnecessary. Bleeding symptoms may be thought to be from other causes. Low platelet count may first be considered the result of leukemia, autoimmunity, or other conditions. Heavy menstrual bleeding may be seen as hormonal or gynecological in nature. Surgical solutions, such as hysterectomy, may be carried out unnecessarily as a result of a misdiagnosis of a bleeding disorder. Bleeding may persist and yet remain undiagnosed, presenting a risk of death in traumatic situations. Testing for vWd to measure  levels, function, severity, and type Severity can be mild, moderate, or severe. Types include type 1 (70 - 80% of all cases), type 2, and type 3 (rare and severe). Type 1 is decreased vWf activity. Type 2 is abnormal vWf. Type 3 is no vWf at all. First, a hematologist, specializing in bleeding disorders, needs to be found. Specialized labs are necessary since many community labs are not equipped to undertake these diagnostic tests. Diagnostic testing includes: Bleeding Time – length of time needed to stop the bleeding of a small laceration Factor VIII:C –measures amount of factor VIII activity vWfAntigen – measures amount of vWf Ristocetin Cofactor Activity – measures vWf function vWf Multimers – measures structure of vWf molecule Platelet Function Tests – measures how well platelets work in the laboratory Test results may not be accurate Test results may be affected by many variables in the patient as well as the lab technician. Results are influenced by: Menstrual cycle Use of aspirin or non-steroidal anti-inflamatories Cold environment Birth control pills, hormone therapy, pregnancy, breast feeding, and childbirth Exercise, stress, and crying Tests may need to be repeated several times, over several months, before a diagnosis can be confirmed. Treatment for vWd Mild bleeds may be treated with pressure and are often self-limiting. Commonly used medications for more severe bleeding include: Hormones found in oral contraceptives administered intravenously, orally, topically, or by patch application. Localized bleeding in the nose or mouth may be treated at the site with Thrombinar, Avitene, or Instat followed by a medication such as Amicar. For more severe bleeds, DDAVP, a synthetic hormone that causes the body to release its own stores of vWF and FVIII, is successful with type 1. This is administered by intravenous injection or nasal spray. Intermediate purity FVIII products can be used for vWf type 2 and 3 by injection.   This acts as a replacement as it does in people with hemophilia. Recombinant and monoclonal FVIII products do not contain any vWf and cannot be used. Although not a treatment, pregnancy can often decrease vWd symptoms. If you believe that you may have a bleeding disorder and your diagnosis is not yet confirmed, you need to see a hematologist who specializes in hemophilia and related inherited bleeding disorders.  You might contact a nearby hemophilia treatment center.  For their locations, check our listing.  If your diagnosis is confirmed, and you need prescription medication, we are here for you.  Please do not hesitate to contact AHF at 800-243-4621 E-mail. If you are a medical or other professional whose clinical or administrative responsibilities place you in a position to make decisions about hemophilia care, please review our professional education section.  We offer seven CEU presentations, that we can bring to your hospital, clinic, or institution, time and schedule permitting.  Among these, we offer the following on-line presentation: 1 - credit CEU on von Willebrand disease. AHF does not dispense medical recommendations nor advice on specific treatments for specific individuals.  For that, we recommend contacting your physician or medical center. The above information is based upon several publications of the National Hemophilia Foundation (NHF) including Understanding von Willebrand Disease, Exploring von Willebrand Disease and A Guide for Women and Girls with Bleeding Disorders.   Setting the Standard of Homecare for the Bleeding Disorders Community