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Dangers Women With Abnormal Bleeding Face

Simple lab tests give long-awaited answers for abnormal bleeding

By Martha Frase | 02.07.2011
Originally Published March 2010
Young woman with von Willebrand disease

Many women accept heavy, prolonged periods as an annoying but ordinary condition, putting up with monthly fatigue and stress. It may take years before they are tested for a bleeding disorder or hear about von Willebrand disease (VWD) as a potential cause of their excessive bleeding.

While men and women are equally affected by VWD, in women, heavy menstrual bleeding (menorrhagia) is often the major symptom. However, not every woman with heavy bleeding has VWD.

The complex diagnostic process for VWD usually begins with a few questions about family and menstrual history. “If someone has had heavy bleeding since her first period, that raises suspicions. A family history of known bleeding disorders, such as hemophilia, would as well,” says Andrea S. Lukes, MD, MHSc, president and CEO of Carolina Women’s Research and Wellness Center in Durham, NC. Lukes is also the founder and chair of the Ob/Gyn Alliance, a peer-to-peer network educating ob/gyns.

The initial step to determine if a patient has VWD is to run specific tests that measure VW antigen (the amount of VW protein in the blood) and activity levels (how well the VW protein works), and levels of factor VIII (FVIII).

“The range of normal for antigen and activity will vary from 50% to 150%,” says Alice Ma, MD, associate professor of medicine in the Division of Hematology/Oncology at UNC Hospitals in Chapel Hill, North Carolina. “But there’s normal, and then there’s ‘normal.’” The difference is in the patient’s story, according to Ma, a hematologist who specializes in treating women with bleeding disorders.

Some physicians may send an initial screening test for VWD called a platelet function assay (PFA) test. However, there is conflicting data as to the sensitivity and specificity of this test for VWD, and the National Institutes of Health does not recommend PFAs as routine tests.

A PFA test determines the time it takes, in seconds, for platelets floating in blood to stick to an artificial substance that mimics an injured blood vessel.

When Retesting Is Required

Because test results can come back normal for a person with VWD due to several factors, such as stress, elevated estrogen levels, pregnancy, use of oral contraceptives and recent physical exertion, retesting can be required. Test results may also be skewed during periods of acute inflammation, such as the perioperative period, and if infections are present. Any of these can temporarily increase the VW antigen and activity levels into the acceptable range. “For a patient with a level of 50%–60%, but in the setting of a really good story—a history of bleeding and a strong family history of bleeding disorders—I am going to repeat those tests, making sure everything is optimized for the best results,” Ma says.

“I may bring a patient back to be tested again right before menstruating [when hormone levels are lower], or take her off birth control pills or HRT [hormone replacement therapy] for a month or two before repeating the test,” says Ma. “Also, if a patient has just run up the stairs or is nervous, [those factors] can increase levels as well. I will bring her back on another day, make sure she takes the elevator and try to keep her calm.” She adds that some of her colleagues, especially those working with children, will keep patients in a dark, quiet room or even use biofeedback to reduce stress before testing.

Another factor that can affect VWD test results is where the testing is done. “It is best to get the tests done by a hematologist, preferably one associated with a hemophilia treatment center,” Ma says. Commercial labs or clinics may not use optimal methods for handling blood. “If it sits outside in a metal box, the sample could be messed up before it gets to the lab.”

Getting Answers

Diagnosis of VWD typically takes three to four weeks; the findings will show the type and severity of VWD. There are three different types of VWD: 1, 2 and 3. (In addition, type 2 has several subtypes.) In type 1, the VW protein is normal but is produced in decreased amounts—levels range from 20% to 50%. Symptoms are typically mild. In type 2, the VW protein is abnormal. Patients with type 3 VWD have very low levels of VWF activity and antigen (typically less than 10%), and low factor VIII levels. They typically have severe symptoms.

The levels of von Willebrand factor antigen and activity, the ratio between them and the multimeric analysis help distinguish among the various subtypes of type 2 VWD. The multimeric analysis is a study of the makeup of the VW protein and is abnormal in type 2A and 2B. Type 2A and 2B will have very low levels of activity, but the antigen levels may be normal even if the multimeric analysis is abnormal.

Type 1 should be treated with DDAVP, or desmopressin acetate, a synthetic hormone released through a nasal spray, according to the National Hemophilia Foundation’s Medical and Scientific Advisory Council (MASAC) recommendations on VWD treatment. DDAVP increases the levels of FVIII and VWF circulating in the blood for up to eight hours after administration. People with types 2A, 2M and 2N VWD should be treated with DDAVP if they have responded positively to a trial of DDAVP. People with subtypes 2B and type 3 VWD (and those with types 1, 2A 2M and 2N who don’t respond to DDAVP) should be treated with VWF-containing FVIII concentrates, according to MASAC recommendations. For some women, heavy menstrual bleeding can be controlled with hormone replacement therapy or birth control pills.

Medications called “antifibrinolytics” can also be used to treat heavy periods. For years, the only available option in the US has been aminocaproic acid. However, LystedaTM, the oral form of tranexamic acid, was approved by the US Food and Drug Administration in November 2009. It is expected to be available in the US in early 2010.

To those undergoing testing or who are newly diagnosed, Lukes offers this assurance: “Once you are diagnosed, it’s the first step to managing the disease. There are lots of options to control its impact. I see a huge sense of relief come over individual women when they finally understand why they have this bleeding disorder and how common it really is.”