Non-Pregnant Vaginal Bleeding: Differential Diagnosis, Presentation, Evaluation, and Management

Authors: Emily Guy, MD (EM Resident Physician, University of Vermont), Julie T. Vieth, MBChB (@JulieTVieth, EM Attending Physician, Canton-Potsdam Hospital, NY) // Reviewed by: Marina Boushra, MD; Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

Case

A 17-year-old G0 presents to the emergency department (ED) complaining of heavy vaginal bleeding and syncope. She is otherwise healthy and takes no medications. Her last menstrual period was 4 weeks ago, and she complains that her menstrual periods are always heavy. Triage vital signs include a blood pressure of 90/47 mmHg and the pulse of 98 bpm. On exam, she appears pale and has cool extremities. During examination, she begins to complain of lightheadedness, and a repeat set of vital signs is notable for a blood pressure of 77/30 mmHg and a heart rate of 112 bpm. A urine pregnancy test is negative.


Introduction

Abnormal vaginal bleeding is a common complaint in the ED and affects approximately 20-30% of women during their reproductive years.1 The presentation of abnormal vaginal bleeding can result from abnormal uterine bleeding (AUB), bleeding from the cervix, or bleeding from the infracervical vaginal structures. A normal menstrual cycle lasts 4.5 to 8 days and occurs at an interval of 24 to 38 days.2 AUB is defined as bleeding from the uterine corpus that is abnormal in regularity, volume, frequency or duration and which occurs in the absence of pregnancy.3,4  AUB can be classified as acute or chronic. Acute AUB is defined as vaginal bleeding sufficient to require immediate intervention to prevent further blood loss.3 AUB is considered chronic if it has been present for most of the previous six months.3


Initial Evaluation

Initial evaluation of a patient with vaginal bleeding should begin with the ABCs. Be sure to quickly assess for hypovolemia and hemodynamic instability.  If the patient appears unstable, insert two large-bore IVs and prepare for blood transfusion and clotting factor replacement as needed.

All patients of reproductive age (generally considered age 12-52) with vaginal bleeding should get a pregnancy test as soon as possible. This result will affect the diagnostic algorithms and treatment pathway. The rest of this review will focus on the evaluation and treatment of non-pregnant vaginal bleeding.


History and physical examination

Obtain a focused history regarding the patient’s current bleeding episode. Questions should aim to answer the following:

  • Bleeding pattern
    • Frequency of bleeding
    • Any intermenstrual bleeding
    • Regular or irregular in timing
  • Quantity of bleeding, which can be estimated by the number of tampons or sanitary pads used (a regular tampon/pad can hold 20-30ml of blood and should not have to be changed more frequently than every 2 hours)4
  • Presence of large clots
  • Presence of pain
  • Recent gynecologic interventions or trauma

A gynecologic history must be obtained, including previous menstrual history, sexual activity and contraceptive use, history of abnormal pap smears, gynecological interventions or surgeries, and if applicable, a postmenopausal history. An obstetrical history is also necessary and should include the number of pregnancies with outcomes, complications, and delivery type.

Review of the patient’s medical history should include an assessment for underlying coagulopathy, especially adolescents and young adults. Ask patients about consistently heavy periods since menarche, postpartum hemorrhage, any unexplained or unanticipated bleeding with surgery or dental work, excessive bruising, recurrent epistaxis, gum bleeding, and if there is a family history of bleeding disorders.5 Underlying thyroid, liver, and endocrine diseases including PCOS can all lead to heavy bleeding. Be sure to review the patient’s medication list. Contraceptives, anticoagulants, selective serotonin reuptake inhibitors (SSRIs), tamoxifen, and even herbal supplements such as ginseng, gingko, and soy supplements can cause increased vaginal bleeding.

The physical examination should assess for signs of hypovolemia or anemia. Look for any signs of trauma. Examine the skin for ecchymosis or petechiae suggestive of an underlying coagulopathy. A chaperoned pelvic examination is an important part of the exam in patients with vaginal bleeding. Begin by assessing the external genital region for non-vaginal causes of bleeding, such as bleeding from the rectum, urethra, or labia. Perform a speculum examination to identify signs of trauma to the vaginal vault, assess for vaginal or cervical lesions, look for any retained foreign bodies, and quantify the amount of bleeding. A bimanual exam can elucidate uterine or ovarian enlargement or irregularity.


Causes

Non-pregnant vaginal bleeding can be divided into uterine and extrauterine sources. Abnormal uterine bleeding can be further classified by structural and nonstructural causes, which is important for determining the most effective long-term management. The causes of non-pregnant uterine bleeding can be remembered using the mnemonic PALM-COEIN:3,4

Common causes of abnormal uterine bleeding can also be age dependent:

  • Adolescence: anovulatory cycles and bleeding disorders
  • Reproductive years: pregnancy-related complications
  • 30s: structural causes such as fibroids and polyps
  • Perimenopausal: anovulatory cycles
  • Postmenopausal: malignancy, atrophic vaginitis, exogenous hormone use

 

Structural Causes:

  • Polyps:
    • Endometrial or endocervical
    • Most often benign
    • Often cause intermenstrual bleeding (bleeding between normally-timed periods)
    • Diagnosed by ultrasound (US) or hysteroscopy
  • Adenomyosis:
    • Endometrial glands and stroma invade the myometrium
    • Patients often have painful, heavy periods starting in 30s to 40s
    • Bimanual examination may reveal a large, boggy uterus
    • Diagnosed by US
  • Leiomyoma (Fibroids):
    • Most common benign pelvic tumors
    • Most are asymptomatic, but can cause pelvic pain and abnormal bleeding
    • Large fibroids may be palpated on bimanual examination
    • Diagnosed by US
  • Malignancy:
    • Consider endometrial hyperplasia in any women >45-years, or <45-years with a history of obesity, PCOS, or unopposed estrogen
    • All patients with post-menopausal bleeding need a referral for US and biopsy

 

Nonstructural Causes:

  • Coagulopathy:
    • Causes up to 20% of abnormal uterine bleeding in adolescents6
    • Von Willebrand’s disease is the most common cause
    • Also consider myeloproliferative disorders, ITP, anticoagulation use, and liver disease
  • Ovulatory Dysfunction:
    • Most often seen in adolescents, perimenopausal patients
    • Can also occur in patients with PCOS, liver disease, renal disease, exogenous hormone use, and thyroid disease
    • Eating disorders, weight loss, increased stress, exercise can also suppress the hypothalamus-pituitary-adrenal axis and cause anovulatory cycles
    • Typically present with irregular and heavy bleeding; patients often have prolonged amenorrhea with periodic heavy bleeding
  • Endometrial Causes:
    • Patients have normal ovulatory cycles and structurally normal uterine cavity
    • May have associated breast tenderness, abdominal bloating, pelvic pain
    • Diagnosis is made in patients with heavy menstrual bleeding and no other identified abnormalities
  • Iatrogenic:
    • Oral contraceptive pills (OCP) are the most common cause of intermenstrual bleeding
    • 40% of patients on OCPs will have abnormal bleeding in the first 6 months
    • Bleeding after 6 months of OCP treatment or that recurs after amenorrhea is established should prompt further evaluation by gynecology

Extrauterine causes of vaginal bleeding include:

    • Infectious: PID, endometritis, cervicitis, vaginitis
      • Can be identified on pelvic examination
      • Treatment of the infection will treat the bleeding
    • Cervical erosions or polyps, vaginal or perineal trauma, retained foreign body
      • Can be identified on pelvic examination
      • Cervical erosions or polyps should have close follow-up with a gynecologist
      • Vaginal or perineal trauma may require suture repair. Be sure to question patients privately about sexual abuse or assault.
      • Retained foreign bodies are most commonly tampons. These can be gently removed with a forceps.
    • If recently pregnant, consider retained products of conception or uterine atony

Evaluation

Obtain a urine pregnancy test early in all patients who present with vaginal bleeding.  If a urine sample is not readily available, then obtain a serum qualitative pregnancy assay. If the patient appears unstable, a type and crossmatch is necessary to prepare for transfusion. In stable patients, a hemoglobin level can be helpful to identify anemia.  However, hemoglobin levels take time to drop following blood loss and may be falsely reassuring in a patient with acute, severe bleeding. Consider a TSH if not recently obtained. Coagulation studies can be useful if the history and physical is concerning for coagulopathy.

Transvaginal ultrasound is the imaging modality of choice in vaginal bleeding. This can be performed emergently or as an outpatient depending on the patient’s clinical status, pain, examination findings, and gynecologic follow-up. Do not delay resuscitation or treatment of massive uterine bleeding for imaging studies.


Treatments

Massive Uterine Bleeding

If the patient is hemodynamically unstable, begin resuscitation with fluids and blood products per for a goal mean arterial pressure (MAP) of 60-65mmHg. Reverse any medication-induced coagulopathy, and immediately consult gynecology. While performing ongoing resuscitation, initial treatment in the ED should focus on medical management. Hormonal agents are first-line treatment:

  • Conjugated estrogen 25mg IV q4-6hrs7
    • Contraindicated in patients with a history of blood clots or cardiovascular disease
  • Consider tranexamic acid (TXA) 1300g PO q6-8hrs or 10mg/kg (max 600mg) IV8
    • Higher risk for thromboembolic sequelae with IV administration; discuss with gynecology the risks and benefits if considering IV
  • Consider desmopressin acetate in patients with concern for von Willebrand’s disease9
    • Must be typed and screened for antibodies prior to administration to prevent life-threatening reactions

Be prepared to utilize intrauterine tamponade if bleeding is uncontrolled with medical management. Definitive treatment will likely be provided by gynecology or interventional radiology. Temporizing methods include:

For intrauterine causes: Intrauterine tamponade with a 26F foley catheter inflated with 30ml of saline10, 11

Vaginal packing may tamponade cervical or infracervical sources of bleeding. Notably, while vaginal packing with betadine-soaked gauze may be used as a temporizing measure in suspected uterine bleeds, the packing can mask the true extent of the bleeding and does not provide the same level of tamponade as intrauterine balloon.11

Definitive management may require surgical intervention. It is important to involve gynecology early in the case of massive uterine bleeding. If gynecology services are not available, then consider transferring the patient to a center with an on-call gynecologist while continuing to stabilize the patient.

  • Options include hysteroscopy, endometrial ablation, myomectomy, D&C, and emergent hysterectomy12, 13
  • In some cases, interventional radiology may perform a uterine artery embolization.

 

(Stable) Heavy Uterine Bleeding

Oral contraceptive pills (OCPs), NSAIDs, and oral TXA are the most common medications used in the treatment of stable vaginal bleeding.14

  • OCPs15:
    • Any combination OCP (0.25 milligram norgestimate and 0.035 milligram ethinyl estradiol) can be prescribed three times daily for seven days
    • On average, stops bleeding in three days
    • Regular OCP use results in a 50% decrease in future heavy menstrual bleeding
    • Bleeding can return when the medication is stopped
  • NSAIDs:
    • 400mg ibuprofen every six hours from the first day of the period until bleeding stops
    • Decreases both pain and blood loss by altering the arachidonic acid cascade to increase vasoconstriction and platelet aggregation
  • Progestin-only therapy:
    • Use instead of combined OCPs if there is concern for endometrial pathology or hyperplasia
    • Medroxyprogesterone acetate 20mg three times daily for seven days or 10mg once daily for ten days
  • Oral TXA:
    • 1300mg PO three times daily for five days
    • Antifibrinolytic effects decrease the volume of menstrual blood loss by 26-60%16

Disposition and Follow-Up

If the patient appears unstable, consult gynecology immediately while stabilization is ongoing. These patients will likely require admission for transfusions or definitive surgical treatment.

If the patient appears stable, they can be safely discharged home with close gynecology follow-up. All patients with AUB >45 years old, or <45 years old with obesity or PCOS require gynecology referral for an outpatient endometrial biopsy to assess for endometrial hyperplasia or malignancy.


Takeaways:

  • Initial evaluation should assess for hypovolemia and hemodynamic instability. If the patient is unstable, follow the tried-and-true tenants: large bore IVs, monitors, resuscitation with blood products.
  • Perform a focused gynecologic history and physical examination, including a chaperoned pelvic examination, to assess for the underlying cause of heavy vaginal bleeding.
  • Initial treatment should focus on medical management:
    • Massive bleeding: conjugated estrogen 25mg IV +/- TXA 1300mg PO or 10mg/kg IV
    • Stable bleeding: OCPs, progestin-only pills, NSAIDs, oral TXA
  • The need for surgical treatment depends on the patient’s stability, severity of bleeding, response to medical management, or contraindication to medical management.
    • Consult gynecology early in patients with severe bleeding.
    • Attempt tamponade with a 26F foley inflated with 30ml saline.
  • May pack the vagina with betadine-soaked gauze as a temporizing measure. Close follow-up with gynecology is recommended even for stable patients.

References/Further Reading

  1. Kjerulff KH, et al. Chronic gynecological conditions reported by US women: findings from the National Health Interview Survey, 1984 to 1992. Am J Public Health. 1996;86:195–199.
  2. Tintinalli, et al. Tintinalli’s Emergency Medicine Manual. Chapter 96: Abnormal Uterine Bleeding. New York : McGraw-Hill Medical, 2012. Print.
  3. Munro MG, et al. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. FIGO Working Group on Menstrual Disorders. Int J Gynaecol Obstet 2011;113:3–13.
  4. Diagnosis of abnormal uterine bleeding in reproductive-aged women. Practice Bulletin No. 128. American College of Obstetricians and Gynecologists. Obstet Gynecol 2012; 120:197–206.
  5. Kouides PA, et al. Hemostasis and menstruation: appropriate investigation for underlying disorders of hemostasis in women with excessive menstrual bleeding. Fertil Steril 2005;84:1345–51.
  6. Kadir RA, et al. Frequency of inherited bleeding disorders in women with menorrhagia. Lancet 1998;351:485–9.
  7. DeVore GR, et al. Use of intravenous Premarin in the treatment of dysfunctional uterine bleeding —a double-blind randomized control study. Obstet Gynecol 1982;59:285–91.
  8. Lukes AS, et al. Tranexamic acid treatment for heavy menstrual bleeding: a randomized controlled trial. Obstet Gynecol 2010;116:865–75.
  9. Kadir RA, et al. Management of excessive menstrual bleeding in women with hemostatic disorders. Fertil Steril 2005;84:1352–9.
  10. James AH, et al. Evaluation and management of acute menorrhagia in women with and without underlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol Reprod Biol 2011;158:124–34.
  11. Hamani Y, et al. Intrauterine balloon tamponade as a treatment for immune thrombocytopenic purpura-induced severe uterine bleeding. Fertil Steril 2010;94:2769.e13–2769.e15.
  12. Bowkley CW, et al. Uterine artery embolization for control of life-threatening hemorrhage at menarche: brief report. J Vasc Interv Radiol 2007;18:127–31
  13. Nichols CM, Gill EJ. Thermal balloon endometrial ablation for management of acute uterine hemorrhage. Obstet Gynecol 2002;100:1092–4.
  14. National Collaborating Centre for Women’s and Children’s Health, National Institute of Clinical Excellence. Heavy menstrual bleeding. Clinical guideline . London: RCOG Press; 2007.
  15. Munro MG, et al. Oral medroxyprogesterone acetate and combination oral contraceptives for acute uterine bleeding: a randomized controlled trial. Obstet Gynecol 2006;108:924–9.
  16. Lemineh, H and Hurskainen, R. Tranexamic acid for the treatment of heavy menstrual bleeding: efficacy and safety. Int J Womens

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