Continuing Education Activity

Abnormal uterine bleeding (AUB) is the name given to describe any deviation from the normal menstrual cycle. The average cycle lasts 29 days with a range of 23-39 days with bleeding episodes lasting 2-7 days. The International Federation of Gynecology and Obstetrics (FIGO) and the American Congress of Obstetricians-Gynecologist have endorsed the PALM-COEIN classification system that divides AUB into structural and non-structural causes. This activity will discuss the aspects of acute AUB in non-pregnant reproductive-age women when it is of sufficient quantity to require prompt intervention to prevent further blood loss. This activity highlights the role of the interprofessional team in caring for patients with this condition.

Objectives:

• Recall the causes of menorrhagia.
• Describe the workup of a patient with menorrhagia.
• Summarize the treatment of menorrhagia.
• Review the importance of improving care coordination among interprofessional team members to improve outcomes for patients affected by menorrhagia.

Introduction

Abnormal uterine bleeding (AUB) is the name given to describe any deviation from the normal menstrual cycle. The average cycle lasts 29 days with a range of 23-39 days with bleeding episodes lasting 2-7 days. The International Federation of Gynecology and Obstetrics (FIGO) and the American Congress of Obstetricians-Gynecologist have endorsed the PALM-COEIN classification system that divides AUB into structural and non-structural causes.[1] The PALM-COEIN table is available for review under the etiology section of this article and has led to the terms menorrhagia (prolonged or excessive bleeding), oligomenorrhea (bleeding greater than 35 days), intermenstrual bleeding (bleeding between cycles), and postmenopausal bleeding to fall out of favor. At least 30% of hysterectomies performed in the USA are for heavy menstrual bleeding.

This activity will discuss the aspects of acute AUB in non-pregnant reproductive-age women when it is of sufficient quantity to require prompt intervention to prevent further blood loss.

Etiology

Menorrhagia, or abnormal uterine bleeding (which is the preferred terminology), can be classified into nine categories making up the PALM-COEIN acronym. This table divides AUB into structural and non-structural causes:

• Polyp
• Adenomyosis
• Leiomyoma
• Malignancy and hyperplasia
• Coagulopathy
• Ovulatory dysfunction due to hypothyroidism, hyperthyroidism, prolactin-secreting tumors, PCOS
• Endometrial
• Iatrogenic (IUDs, chemotherapeutic agents, anticoagulants)
• Not yet classified           

It is essential for the provider to choose the most likely etiology for the effective and appropriate management of these women.[2]

Epidemiology

Abnormal uterine bleeding, or menorrhagia as previously classified, is a predominant complication among women in the United States that is related to the major impacts of women's quality of life, productivity, and healthcare cost. Reports are that the annual prevalence rate is 53 per 1000 women.[3] In the outpatient setting, AUB is one of the leading causes of outpatient gynecological visits with 20-30% of women presenting with this complaint annually.[4]

Pathophysiology

The pathophysiology of abnormal uterine bleeding (AUB) is as diverse as the classification of the disease. AUB can be caused by pelvic pathology like a distortion of the endometrial cavity due to fibroids, or endometrial protrusions into the cervix or vagina (polyps), or because of friable endometrial tissue. The friable endometrial tissue is likely caused by unopposed estrogen which causes the endometrium to become friable, vascular, and lacking sufficient stromal support which equates to heavy, continuous uterine bleeding.

Systemic conditions are also responsible for AUB. Obesity is an epidemic whose consequences affect every aspect of life and every organ system. In women, obesity can lead to unopposed estrogen and can lead to the polycystic ovarian syndrome. Coagulopathies can also lead to AUB; 13% of women with AUB have a variant of Von Willebrand disease, and 20% have an underlying coagulopathy.[4]

Another important consideration and a significant cause of AUB are the patient’s medications. An intact coagulation pathway is essential for menstrual regulation and medications that interact with platelets and coagulation factors can lead to Acute AUB. The following is a list of some medications that can lead to AUB:

• Warfarin, aspirin, clopidogrel, and other anticoagulants
• Conceptive medications and devices
• Tamoxifen
• Tricyclic antidepressants
• Antipsychotics
• Corticosteroids

History and Physical

Obtaining a complete history and physical, focused on questions directed towards PALM-COEIN etiologies will allow the provider to narrow the likely etiologies. It is important for the clinician to gain a complete understanding of the current bleeding episode, a history of her menstrual cycles, gynecological and obstetrical histories, medical and surgical history, current medications, sexual history, and family history. Women who report changing pads/tampons every 3 hours and report clots are likely to have a blood loss of at least 80mL.[5] As mentioned previously, a large percentage of women who present with acute AUB will have some form of coagulopathy, with von Willebrand disease being the most common.[4]

To evaluate the history of bleeding disorders, there is an already established clinical screening tool to assist the provider in determining if the patient will benefit from further coagulopathy testing. A positive screening,[6] includes the following:

• Heavy menstrual bleeding since menarche
• One of the following conditions:
  • Postpartum hemorrhage
  • Surgery-related bleeding
  • Bleeding associated with dental work
• Two or more of the following
  • Bruising 2x per month
  • Epistaxis, 1-2 times per month
  • Frequent gum bleeding
  • A family history of bleeding symptoms

The physical exam should initially be aimed at assessing life-threatening conditions caused by acute blood loss, anemia, and hypovolemia. It is also essential to confirm the cause of acute uterine bleeding. A speculum exam should be performed to thoroughly investigate the genital tract to rule out trauma or other etiologies of bleeding. A bimanual exam will also be essential to evaluate for uterine abnormalities and enlargement caused by leiomyomas, or cervical abnormalities caused by polyps or cervical cancer.

Evaluation

Laboratory evaluation of the patient is essential in guiding the treatment and management of the patient. The initial labs on every patient include complete blood count, blood type and crossmatch, and a pregnancy test. Additional important tests for guiding care for the patient include thyroid-stimulating hormone, iron studies, liver function test, and sexually transmitted disease testing. If the clinical suspicion of coagulopathy is present, it would also the recommendation is that testing for von Willebrand disease and initial coagulopathy labs be performed.[7]

A pelvic ultrasound may help identify the presence of any lesions, shape, and size of the uterus and assess the adnexa.

An endometrial biopsy is recommended in women at risk fo uterine cancer, hyperplasia or polyps.

Treatment / Management

With respect to treatment and management, the initial goal is to stabilize the patient’s hemodynamics. If the patient is unstable, the patient should have two large-bore IVs, airway assessment, and have a type and cross in preparation for blood transfusion. For the unstable patient before surgical interventions, intrauterine tamponade should be performed. A Bakri balloon can be inserted into the uterus to tamponade uterine bleeding. If an intrauterine balloon is not available, gauze packing is an acceptable option. The physician should use a continuous piece to eliminate the risk of retained products. If the bleeding is uncontrolled with tamponade, surgical intervention is necessary. The discussion here will cover the standard surgical intervention, while coverage of alternate options will be in the surgical treatment section of this paper.

The standard surgical intervention for the hemodynamically unstable patient is uterine dilatation and curettage (D&C). This procedure can be performed rapidly with decreased bleeding within 1 hour. D&C with hysteroscopy may be more beneficial in identifying a cause for uterine bleeding but is not mandatory. The disadvantage of D&C for acute uterine bleeding is that this procedure will only provide temporary relief. The procedure will not treat the underlying causes, so medical therapy must start upon cessation of uterine bleeding. One study showed that decreased menstrual blood loss was only evident in the first period after the procedure but subsequently returned to baseline.[8]

For the stable patient, the goal is to control the current bleeding and decrease any future bleeding episodes. The first-line treatment for acute abnormal uterine bleeding is hormonal therapy. There are multiple options available, including oral contraceptive pills (OCPs), IV estrogen, medroxyprogesterone acetate, and tranexamic acid.

IV conjugated estrogen is the only FDA specially approved treatment for acute AUB, due to the limited studies. One randomized control study showed that IV conjugated estrogen stopped bleeding for 72% of patients within 8 hours with the majority of those women showing results at 5 hours.[9]   The mechanism of action of estrogen therapy is the rapid regrowth of the endometrium over the exposed epithelial surface.

The recommended dose is 25mg IV every 4-6 hours for 24 hours. After 24 hours, the patient should transition to oral combined contraceptive pills or progestin to decrease unopposed estrogen exposure. The contraindications for IV estrogen are as follows:

• Current diagnosis of breast cancer
• Active or past venous thrombosis
• Arterial thromboembolic disease
• Liver dysfunction
• It should be used with caution in women with cardiovascular and thromboembolic risk factors         

Combined oral contraceptive pills and oral progestins are commonly used medications for acute AUB. One study showed that treatment with either medication taken for one week stopped the bleeding in 3 days for 76-88% of women. The recommended treatment regimen for monophasic combined oral contraceptive pills that contain a minimum of 35mcg of ethinylestradiol is three times a day for seven days.[10]Contraindications include:

• >35 years of age and cigarette smoking
• Hypertension
• History of deep vein thrombosis (DVT) or pulmonary embolism (PE)
• Known thromboembolic disease
• Cerebrovascular disease
• Ischemic heart disease
• Migraine with aura
• Current or past breast cancer
• Severe liver disease

The treatment regimen for progestins is medroxyprogesterone acetate 20mg orally three times a day for seven days. The contraindications include:

• Active or past DVT or PE
• Arterial thromboembolic disease
• Current or past breast cancer
• Impaired liver function

Tranexamic acid received approval for the treatment of AUB in 2009. This drug is an antifibrinolytic that reversibly binds to plasminogen preventing fibrin degradation. The recommended treatment regimen is tranexamic acid 1-1.5g orally every 8 hours for five days or 10mg/kg IV (max dose 600mg/dose) every 8 hours for five days.[7] Contraindications include:

• Current thrombotic disease
• Used with caution in patients with a history of DVT, PE

As mentioned previously D&C is the current surgical treatment of choice for acute AUB; however, the other surgical options available to providers are endometrial ablation, uterine artery embolization, and hysterectomy. Endometrial ablation is an effective treatment in women who have contraindications to the medical therapies mentioned above. This procedure should only be performed on women who no longer desire fertility and when the possibility of endometrial or uterine cancer has been ruled out as possible causes of acute AUB.[11] Uterine artery embolization is the first-line treatment for women with the rare etiology of uterine bleeding from a uterine arteriovenous malformation. The physician should not use this procedure on the unstable patient since other options are more readily available.[12] A hysterectomy is the last resort procedure and should only be used after the patient has failed medical therapy or other surgical interventions.

Differential Diagnosis

This paper has already listed the FIGO etiology classification for AUB. The PALM-COEIN classification system list nine different differentials for the provider to consider. This section will cover some additional diagnoses that are important differentials in the emergency department. The uterus is the only organ for which bleeding represents a normal physiologic process, and might mask other etiologies of anemia, especially in peri-menopausal women. The normal menstrual cycle, on average, lasts 4-9 days with a blood loss of less than 80 mL. Molimina symptoms like cramping, mood swings, breast tenderness, and fluid retention precede menstruation. Pregnancy or ectopic pregnancy can often present with vaginal bleeding. All women within the reproductive years should have a pregnancy test as part of their initial workup.

Prognosis

The prognosis of AUB is vastly dependent on the etiology, as classified through the PALM-COEIN system. In women with premenopausal acute uterine bleeding, the prognostic data basis is quality of life; 50% of women presenting with abnormal uterine bleeding present with less than 40mLs of blood loss, meaning that quality of life is driving the decision to seek medical attention.[13]  Quality of life testing suggests that women with AUB will score below the 25 percentile against women of similar age. When evaluating, treating, and managing these patients it is important to not only focus on mortality and morbidity, but also the quality of life. The form used in most research studies is the short form 36 health survey, used in 63% of studies in a meta-analysis review regarding AUB.[14]Recently a heavy menstrual bleeding questionnaire was developed to assist in validating patient-reported outcomes. This form covers a range of symptoms, amount of bleeding, social embarrassment, and fear of social interactions because of AUB. ("The menstrual bleeding questionnaire: development and validation of a comprehensive patient-reported outcome instrument for heavy menstrual bleeding.")[15]

Enhancing Healthcare Team Outcomes

Acute uterine bleeding is a complication that can be emotionally devastating to the patient as well as life-threatening. Because of the diverse number of causes, it is important that the disorder is managed by an interprofessional team. It is crucial for emergency physicians to involve gynecologists in the management of this disease quickly. Nurses in the emergency department should ensure that the patient has adequate access, is NPO and has the blood work submitted. Resuscitative equipment must be in the room. The patient should be educated about the procedures and protocols for dealing with AUB. The radiologist should be informed about the patient in case a pelvic ultrasound is needed. In addition, the operating room has to be notified in case an emergency hysterectomy is necessary. For stable patients, the pharmacist should discuss the hormonal and non-hormonal treatments available to treat menorrhagia.

The collaborative efforts will ensure a quick resolution to the unstable patient as well as appropriate treatment options for the stable ones. The team approach will not only ensure swift, appropriate care and cessation of the bleeding but will ensure long-term follow-up for prevention of future bleeding episodes. With the team approach to patient care, it allows for a direct transition to the outpatient clinic where discussion and implementation of long-term medical or surgical treatment options can take place.