Menorrhagia

Menorrhagia or heavy menstrual bleeding is the more common symptom for women who have a bleeding disorder. It is defined as bleeding that lasts for more than 7 days or results in the loss of more than 80mls of blood per menstrual cycle.

In addition to heavy menstrual loss, women with bleeding disorders suffer from prolonged bleeding (more than seven days), excessive passage of large blood clots and flooding during menstruation. Adolescent girls and peri-menopausal women may suffer the most, as menstrual cycles are often anovulatory (i.e. no egg is released) during these reproductive stages. This leads to irregular shedding of the endometrium (lining of the womb) and predisposes to increased and prolonged menstrual bleeding. Perimenopausal women are also more likely to have pelvic disease, such as fibroids and endometriosis, which increase the risk of bleeding.

It can be hard for any woman to tell if menstrual bleeding is unusually heavy compared to others. In a woman with a bleeding disorder, comparison to other family members can be misleading as they too may have the same bleeding disorder resulting in heavy menstrual bleeding. Nobody sees it as special or if they do, they say, “All the women in our family bleed a lot during their periods.”

• Flow which lasts longer than 7 days
• Flow soaking one pad in less than 2 hours
• Unpredictable bleeding
• Menstrual bleeding which affects quality of life
• Periods heavy enough to cause anaemia.

Dysmenorrhoea (painful periods)

Women with bleeding disorders and carriers more commonly suffer from period pain. Usual treatments include non steroidal  anti- inflammatory drugs such as Nurofen but these should be avoided in women with bleeding disorders because of their anti platelet activity. Alternative painkillers such as paracetamol and codeine based products may be used. The combined oral contraceptives may also help reduce period pain as may an intrauterine system releasing the hormone levonorgestrel (Mirena IUD) (see “Hormonal therapy”)

Haemorrhagic ovarian cysts

When a woman ovulates, a small amount of bleeding may occur with rupture of the egg follicle when the egg is released from the ovary. This may be associated with abdominal and pelvic pain. Women with bleeding disorders are more likely to have significant bleeding at ovulation with resulting pain, haemorrhagic ovarian cysts or even bleeding into the abdominal and pelvic cavity.

Although these gynaecological complications can be treated surgically, non surgical management with the use of appropriate clotting agents (tranexamic acid, DDAVP and coagulation factor replacement) is advisable in women with bleeding disorders. Combined oral contraceptives suppress ovulation and have been successfully used to prevent recurrences

Endometriosis and other gynaecological conditions

Endometriosis is a painful condition in which endometrial tissue, the tissue which lines the uterus, implants in the pelvis and organs outside of the uterus. There is no strong evidence that women with bleeding disorders are more likely to develop endometriosis, fibroids, polyps of the uterus or endometrial hyperplasia (excessive growth of the lining of the uterus) but in a survey of 102 women with vWD by the US Centers for Disease Control, these gynaecological problems were more likely to be reported by women with vWD than women without vWD. Since most of these gynaecological conditions often present with bleeding, women with bleeding disorders are more likely to develop symptoms and therefore to be diagnosed

Menopause

Menopause is the time in a woman’s life when menstrual periods permanently stop. Peri-menopause is a 3 to 10-year period before natural menopause, when hormones are “in transition.” Symptoms of peri-menopause include heavy menstrual bleeding, irregular bleeding and spotting. Since there are other medical reasons for heavy bleeding, and women with bleeding disorders are at the same risk for these problems as other women, a full medical investigation should be done to eliminate other causes of bleeding.  As in all women, the cause of the abnormal menstrual bleeding needs to be determined before any treatment is offered. If the bleeding is caused by lack of ovulation, hormone replacement therapy (HRT) will usually control the problem. However, if a woman is already using HRT, she may need to discuss other options with her gynaecologist and her haematologist. She may require other forms of treatment such as endometrial ablation or a hysterectomy.

It is important that women maintain a strong relationship with their gynaecologist even after childbearing years in order to anticipate the combined issues of menopause and bleeding disorders.

TREATMENT

Combined Hormonal Contraceptives

Combined hormonal contraceptives reduce menstrual blood loss by thinning the endometrium and possibly increasing factor VIII and von Willebrand\’s factor levels. Combined hormonal contraceptives currently available include combined oral contraceptive pill (COC), transdermal contraceptive patches, and vaginal rings. They provide reliable birth control and cycle control and reduce dysmenorrhoea and other menstrual complaints. In women with bleeding disorders, they have an added advantage of controlling ovulation bleeding and midcycle pain. Continuous use of these therapies (rather than the traditional 21-day course) is safe and can be used to control timing and frequency of menstruation as well as menstruation associated symptoms. This can be very useful for women with severe menstrual problems.

Most women who use combined hormonal contraceptives have none or very few side effects. Serious side effects of hormonal contraceptives include high blood pressure, liver abnormalities and clots. Women with bleeding disorders, however, may have a low inherited risk of clotting. Side effects that some women have are nausea, headaches, dizziness, breast tenderness and mood changes. Some of these side effects improve over the first 3 months. If the side effects continue, the doctor may prescribe a different brand of hormonal contraceptive.

Levonorgestrel intrauterine system

Levonorgestrel intrauterine system (LNG-IUS, Mirena®) is the most effective medical treatment for menorrhagia and has been shown to be useful for reducing menstrual blood loss in women with bleeding disorders. It is also an effective and reversible method of contraception making it an ideal treatment for women with menorrhagia who want to preserve their fertility. The licensed duration of use in Ireland is five years i.e. once inserted it may stay in place for 5 years. The main problem is irregular bleeding or spotting, especially within the first 6 months. In women with bleeding disorders, there is a potential risk of bleeding at the time of insertion and preventative treatment with a haemostatic agent may be required.

Oral progestogens

Oral progestogens such as Medroxyprogesterone acetate and Norethisterone are recommended treatments for menorrhagia when used as a 21-day course (days 5-26). Side effects include fatigue, mood changes, weight gain, bloating, depression, and irregular bleeding. In high doses, oral progestogens can be used with DDAVP or clotting factor to treat acute menorrhagia in women with bleeding disorders.

Progestin-only contraceptives

Progestin-only contraceptive such as Depo-Provera (Medroxyprogesterone Acetate) injections, progestin-only pills, and the Implanon implant also reduce endometrial thickening and may reduce menstrual blood loss or stop menstruation. They are associated with a high rate of irregular bleeding and spotting. Insertion of the Implanon implant may also cause bleeding in women with bleeding disorders and preventative treatment with a haemostatic agent may be required.

Gonadotropin-releasing hormone (GnRH) analogues

These drugs stop ovulation and are effective for reducing menstrual flow and duration. Side effects due to reduced oestrogen include hot flashes and loss of bone density (which is reversible). GnRH analogues may be an alternative option to surgery for young women with resistant menorrhagia or severe bleeding disorders. If used for more than six months, hormone replacement therapy should be added to counteract low oestrogen levels.

Haemostatic therapy

Haemostatic therapy may be effective in controlling menorrhagia in women with bleeding disorders. Haemostatic agents constitute the main treatment option for women who are trying to conceive. They are also used in women who do not wish to get pregnant, either alone or in combination with hormonal therapy.

Haemostatic therapies include DDAVP (1-desamino-8-D-arginine vasopressin), tranexamic acid and coagulation factor concentrates.

Oral tranexamic acid also is known as Cyclokapron (1g, 3-4 times a day during the menstrual period) is usually well tolerated but side effects include nausea, headache, and diarrhoea. Tranexamic acid stabilises a clot once it has formed by stopping the activity of an enzyme called plasmin, which dissolves blood clots.

Note: A person with urinary tract bleeding (blood in the urine) should not take this drug.

DDAVP can be given by intravenous injection or intranasally as a spray. For management of menorrhagia, it is usually administered as a nasal spray (150-300mcg daily for a maximum of 3-4 days, usually during days with the heaviest blood flow). Side effects include fast heart rate, flushing and headache. There is also a small risk of reduced sodium (salt) level and fluid retention. Therefore, fluid restriction during treatment is essential. If a person has a very bad headache or has not been able to urinate 24 hours after taking DDAVP, they should contact their Haemophilia Treatment Centre or Emergency Department for advice. In the elderly and in people with cardiovascular disease, desmopressin can cause more serious side effects and may not be recommended.

Both tranexamic acid and DDAVP alone or in combination may be effective in controlling menorrhagia in women with bleeding disorders.

Regular prophylaxis with clotting factor replacement may be required to control menorrhagia in some women with severe factor deficiencies not responding to other treatments. These include plasma-derived factor concentrate or recombinant (genetically engineered) concentrate. All plasma used is screened for blood-borne viruses such as HIV, Hepatitis B and Hepatitis C and treated to inactivate any known viruses.

Surgical Treatment

Surgery may be required in the presence of pelvic disease and for women who do not tolerate medical treatment or in whom this is unsuccessful. Women with inherited bleeding disorders are more likely to have peri-operative and/or delayed (7-10 days later) bleeding, even with relatively minor procedures such as hysteroscopy and biopsy. Therefore, any surgical intervention should be performed in a centre with available laboratory support and an experienced haematologist. Prophylactic treatment may be required pre-operatively to reduce the risk of excessive bleeding. Surgical options include hysterectomy and endometrial ablation. These procedures eliminate the possibility of future pregnancy and are only for women who do not want to have future pregnancy.

Hysterectomy

Hysterectomy is the surgical removal of the uterus, not including the removal of the ovaries and fallopian tubes. Haemorrhage is the most common complication. Others include genitourinary complications, infection, and poor wound healing. A lengthy post operative recovery period is required. Long term complications include early ovarian failure (premature menopause) and urinary and sexual problems. Peri-operative bleeding complications are of specific concern in women with bleeding disorders.

Therefore, hysterectomy should not be the first line treatment but used only when other treatments fail or when pelvic disease indicates its use in women who no longer wish to retain fertility.

Endometrial ablation

Endometrial ablation techniques are now widely used as an alternative to hysterectomy. They may reduce menstrual blood loss in women with bleeding disorders. Endometrial ablation removes a thin layer of the lining of the uterus and stops the menstrual flow in many women. In some women, menstrual bleeding does not stop but is reduced to normal or lighter levels. These procedures have a shorter operating time, recovery time, and complication rate when compared to hysterectomy.

Possible complications are:

• Cramping, like menstrual cramps for 1–2 days.
• Thin, watery discharge mixed with blood, which can last a few weeks
• Frequent urination for 24 hours
• Nausea