Vaginal Bleeding in the Non-Pregnant Patient

Context

Vaginal bleeding, either normal menstruation or abnormal bleeding, affects almost all females at some point in their lives and many of these patients are sufficiently concerned to attend the ED.^1–4

Here are some statistics to highlight the scale of the issue:

• Approximately 25% of the UK population are females of reproductive age;⁵
• 14% of women of reproductive age experience abnormal uterine bleeding (AUB):⁶
• Around 5% of GP consultations for women aged 30-49 years relate to heavy menstrual bleeding (HMB).⁷ This does not include the many other causes of vaginal bleeding.

HMB is one of the most common causes of abnormal bleeding. It is defined by the patient’s perception of heavy or excessive bleeding and the affect it has on her life, as opposed to the actual volume of blood lost.^8,9 HMB has a number of consequences for women, leading to the following:

• Iron deficiency anaemia – HMB is one of the leading causes of iron deficiency anaemia in females worldwide:¹⁰
• Blood transfusions and inpatient stays in hospital ;
• Missed days at school or work;
• Psychosocial and sexual difficulties.^9,10

Vaginal bleeding can also be a symptom of cancer, particularly gynaecological malignancy, but also haematological cancers. Cancer Research UK report that uterine cancer is the fourth most common cancer in women in the UK, with approximately 9,400 new diagnoses and 2,400 deaths each year.¹¹ Many of these patients present with AUB. Postmenopausal bleeding (PMB) is of particular concern and in one study, 5-10% of women with PMB were found to have endometrial cancer.¹²

Learning bite

Vaginal bleeding can be a huge problem for women and can be a symptom of serious underlying pathology.

Definitions

Learning bite

Normal menstruation occurs roughly every 4 weeks and less than one pad or tampon is needed every 3 hours.
The definition of heavy menstrual bleeding is based less on actual volume, which is difficult to quantify, and more on the affect it has on the woman’s life.

Follicular Phase

• This is the first half of the cycle and begins with menstruation¹⁶
• The hypothalamus stimulates the pituitary gland to release follicle stimulating hormone (FSH) and leutinizing hormone (LH) which act on the ovary causing maturation of a follicle.¹⁷
• Oestrogen levels rise stimulating the endometrium to proliferate and thicken and also causing an LH surge which triggers ovulation.^16,17

Luteal Phase

• This is the second half of the cycle and begins with ovulation.
• The ruptured follicle evolves into the corpus luteum and secretes progesterone.^16,17
• If the egg is not fertilised, the corpus luteum involutes after 14 days causing a drop in progesterone which triggers sloughing of the endometrium. This is evident as menstrual bleeding.¹⁷
• The first day of the menstrual period marks day one of the next menstrual cycle.¹⁶

Abnormal Vaginal Bleeding

The International Federation of Gynaecology and Obstetrics (FIGO) divides AUB in women of reproductive age into structural and non-structural causes using the PALM-COEIN classification system.¹⁵ Structural causes (PALM) include polyps, adenomyosis, leiomyomas (fibroids), and malignancy whereas non-structural causes (COEIN) include coagulopathy, ovulatory dysfunction, endometrial, iatrogenic and not otherwise classified.¹⁵ It is important to note that the cause of the bleeding may be multi factorial and several causes may coexist.¹⁴

• Structural causes for AUB
  • Polyps
    • Localized tumours of the endocervix or endometrium⁴
    • Usually benign but some have atypical or malignant features¹⁵
    • Often asymptomatic can contribute to AUB¹⁵
  • Adenomyosis
    • Invasion of the myometrium by endometrial tissue⁴
  • Leiomyoma (fibroid)
    • Benign fibromuscular tumours of the uterus
    • Oten asymptomatic but can contribute to AUB^4,15
  • Malignancy and hyperplasia
    • Serious but relatively uncommon cause of AUB¹⁵
• Non-structural causes for AUB
  • Coagulopathy
    • 13% of those with HMB may have von Willebrand’s Disease¹⁸
    • Other patients may have single factor deficiencies or platelet disorders¹⁷
  • Ovarian dysfunction
    • Often no known cause but polycystic ovarian syndrome, hypothyroidism, hyperprolactinaemia, stress, obesity, weight loss, anorexia or extreme exercise can all affect ovarian function¹⁵
  • Endometrial
    • Primary disorder of local endometrial haemostasis¹⁵
  • Iatrogenic
    • A number of drugs and devices can cause or alter uterine bleeding, including:
      • Intrauterine devices – particularly in the first 6 months¹⁵
      • Breakthrough bleeding on oral contraceptives¹⁵
      • Tricyclic antidepressants¹⁵
      • Antipsychotics⁴
      • Anticonvulsants⁴
      • Anticoagulants¹⁵
  • Not yet classified

While the PALM-COEIN system sets out the causes for AUB in women of reproductive age, remember that not all vaginal bleeding is uterine in origin and not all patients are in this age cohort.

Non-uterine causes of vaginal bleeding include:

• Ovarian bleeding
  • More commonly presents with intraperitoneal bleeding but may occasionally present with vaginal bleeding. Causes include cancer, torsion, ruptured cyst.¹⁹
• Foreign body^6,13,17,20
  • E.g. retained tampon, condom
• Trauma of the lower genital tract^21,22
  • Vulva, vagina or cervix
  • Blunt or penetrating trauma
  • May relate to a sexual assault or rape but may have another explanation such as an accidental injury
• Gynaecological infections
  • Pelvic inflammatory disease (PID) is an ascending pelvic infection. It may cause tubo-ovarian abscess, salpingitis or endometritis²² and can present with bleeding.
• Bleeding that is mistakenly reported to be vaginal bleeding e.g. rectal bleeding or haematuria²³

SPECIFIC CAUSES OF VAGINAL BLEEDING IN DIFFERENT AGE COHORTS (1,6,13,22,24)

Learning bite

• Vaginal bleeding can be uterine, or from elsewhere in the genital tract
• Uterine bleeding has structural and non-structural causes
• Differential diagnosis changes depending on the age cohort

When assessing a patient with vaginal bleeding, there are 2 essential questions to be asked immediately which will drastically alter your assessment and management:⁴

1. Is she haemodynamically stable?
2. Is she pregnant?

If she is stable and non-pregnant proceed with routine history and examination. Vaginal bleeding in non-pregnant women is rarely life-threatening,¹³ but if the patient is unstable, proceed with resuscitation in parallel to assessment. If she is pregnant, your assessment and management change depending on gestation and presentation but this is beyond the scope of this session.

History

Examination

NICE states that pharmacological treatment for HMB can be considered without physical examination if the patient has no associated symptoms such as pain, pressure or persistent intermenstrual bleeding,⁸ but many patients attending ED will require examination.

• Vital signs
  • Blood pressure may initially be normal despite large volume blood loss in the young, healthy population¹⁷
  • It is likely that the patient will be tachycardic before their blood pressure drops¹
• Abdominal examination
  • Look for a mass, localised tenderness or signs of peritonism¹⁷
  • Normal uterus and ovaries should not be palpable on abdominal exam⁹
• Pelvic examination

BRING A CHAPERONE AND MAINTAIN PATIENT DIGNITY EVERY TIME

• Role in the ED is controversial but it may yield valuable information^{13,14,17,20,22}
  • Assess for ongoing bleeding, foreign bodies, signs of trauma and vaginal or cervical discharge on inspection before examining uterine size and contour, adnexal masses or tenderness and cervical motion tenderness¹⁷
  • Avoid pelvic examination in the initial assessment of premenarchal patients¹⁷
• If the source of bleeding is not clearly identified, examination should seek other sources including rectal bleeding¹⁷

Key Features on Assessment for each of the Differential Diagnoses

Learning bite

The 2 key questions at the start of the assessment are: Is the patient haemodynamically stable? Is she pregnant?

Targeted history should focus on the history of the bleeding; gynaecological and obstetric history; bleeding history; medical history and associated symptoms.

Pregnancy status

Pregnancy status is one of the most important details to clarify when dealing with a patient presenting with vaginal bleeding and must be done as a matter of urgency.^13,17 Point of care qualitative urine beta hCG tests are quick and easy to use. Occasionally, however, there may be a delay in obtaining a urine sample. For example, a woman who is hypotensive and shocked may be making little urine, or she may have just emptied her bladder prior to your assessment. Although most point of care tests are licensed for use with urine and/or serum only, these tests have been shown to be just as sensitive when used with whole blood.^25–27 The result should be confirmed with a urine qualitative test +/- a serum quantitative test, but positives should be taken seriously.

Other Laboratory Investigations

Initial laboratory investigations for haemodynamically unstable patients are as follows:^13,17

• Venous blood gas
• Full blood count
• Group and crossmatch
• Coagulation profile
• Renal profile

ED investigations for stable patients include:^4,8,17,21

• Full blood count is indicated for patients with HMB or other significant bleeding.
• Coagulation profile should be sent if the patient is on anticoagulant or there is concern she may have a bleeding disorder.
• STI screen may be indicated if suspicion of infection.
• Testing for systemic causes of bleeding such as renal, liver or thyroid disease should only be undertaken in ED if there are symptoms to suggest an underlying disorder.

It should be noted that in most cases laboratory test results are non-specific and do not contribute to the ED management.²¹

Imaging

Pelvic ultrasound should be considered in cases of severe pain and bleeding to out rule serious structural causes such as haemorrhagic cysts, ovarian torsion, or a degenerating fibroid.²¹ In most cases, however, pelvic ultrasound can be arranged as an outpatient for stable patients as the results rarely change ED management.^4,13,17,21

Learning bite

Beta hCG is the single most important investigation in patients presenting with vaginal bleeding. Most stable patients should have a full blood count checked but do not require further investigation in ED.

Unstable Patients

Life threatening acute vaginal bleeding is rare in non-pregnant patients^2,13,21 but can occur, particularly in the context of trauma or a uterine arteriovenous malformation.¹⁷ Patients should have initial resuscitation as per any other unstable bleeding patient:

• ABCDE assessment and interventions including activation of major transfusion protocol if indicated¹⁷
• Urgent ED gynaecology referra^l4,17,21
• First line treatment for vaginal bleeding in unstable, non-pregnant patients is with high dose IV oestrogen to promote rapid endometrial regrowth.^17,21
  • Although first line treatment, this may not be immediately available in ED. In addition, ED practitioners are unlikely to be familiar with IV oestrogen and so this treatment should be led by the gynaecology team.
• Rarely, uterine tamponade may be required for uncontrolled uterine bleeding.
  • Specific devices are available for controlling uterine haemorrhage, e.g. Bakri Balloon, but they may not be available in the ED.
  • If these are not available, pass a foley catheter through the cervix and inflate the balloon^4,13,17 or alternatively pack the uterus with long continuous gauze.¹³ This must be done with a speculum, under sterile conditions⁴ and with sufficient analgesia.
  • If it is not possible to visualise the cervix due to ongoing bleeding, or the bleeding is from the vagina itself, the vaginal vault can be packed with either commercially available vaginal packing or lubricated continuous gauze.⁴ The gauze may be soaked in tranexamic acid as an adjunct.⁴
• If other interventions are unsuccessful, there may be a role for IV tranexamic acid.¹⁷

Stable Patients

If the patient is stable and not significantly anaemic, she may be treated as an outpatient with one or more of the medical treatments described below.⁴ The aim of treatment is to reduce both the duration and volume of blood loss, to treat anaemia if present, and to restore quality of life.^4,23 Medical treatment of stable, non-pregnant patients with vaginal bleeding can be divided into non-hormonal and hormonal treatments.¹³ When discussing and agreeing a treatment option with the patient, take into account her preferences, comorbidities, cause for the bleeding and other symptoms she is experiencing e.g. pain/pressure.⁸

NICE guidelines permit the initiation of pharmacological treatment for HMB without investigating the cause if the history and/or examination suggests a low risk for structural or histological abnormality e.g. persistent IMB, PCB, pressure symptoms, pain, uterus size or pelvic mass.^8,28

Pharmacological treatment options are as follows:

• Non-Hormonal Treatments
  • Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) e.g. ibuprofen, mefenamic acid, naproxen
    • Promote uterine vasoconstriction, thus reducing HMB.^13,21
    • Different NSAIDs appear to be equally effective at reducing HMB.^13,29
    • Contraindications include hypersensitivity to aspirin or an NSAID, peptic ulcer disease, use of anticoagulants, renal and cardiac impairment etc.
    • Also have analgesic properties which can be useful for dysmenorrhoea.
    • They are as effective as oral contraceptives at reducing HMB but less effective than tranexamic acid and the levonorgestrel-releasing intrauterine system (LIUS) e.g. Mirena coil.²⁹
  • Tranexamic acid
    • Antifibrinolytic which is more effective for the treatment of HMB than NSAIDs and oral contraceptives but less so than the LIUS^21,30
    • Does not appear to be associated with an increase in major adverse events but there is insufficient evidence to assess thromboembolism risk³⁰
    • May be given in conjunction with NSAIDs⁹
  • Iron supplementation
    • Should be started in patients with microcytic anaemia.⁴
    • Vitamin C given in conjunction with iron may improve absorption.⁴
• Hormonal Treatments
  • Combined Oral Contraceptive Pill (COCP)
    • Can be prescribed as a taper to temporize an episode of heavy bleeding.^4,13
    • Most effective for patients with bleeding secondary to anovulation.¹³
    • Contraindications to the COCP include:^4,13
      • Pregnancy
      • Liver disease
      • Severe uncontrolled hypertension
      • History of stroke or thromboembolic event
      • Age>35 in those who smoke
      • History of breast/liver cancer (particularly oestrogen dependent tumours)
      • Cerebrovascular or ischaemic heart disease
      • Hypertriglyceridemia
  • Progesterone Only Pill (POP)
    • May be a safe alternative if the COCP is contraindicated.^4,13
  • Levonorgestrel-releasing intrauterine system (LIUS) e.g. Mirena coil
    • Very effective at reducing HMB²¹ but not typically an option in ED.
    • Can cause an initial change in bleeding pattern, often causing erratic bleeding, particularly in the first few cycles.^8,9

Disposition

Most stable patients can be discharged home with timely gynaecology outpatient follow up.^13,22 Unstable patients and those with significant anaemia may require admission for transfusion and urgent gynaecological inpatient assessment.⁴

1. Not believing the patient – if she says the bleeding is heavy and it is impacting her life then she meets criteria for HMB.
2. Failing to recognise red flag symptoms of malignancy such as postmenopausal bleeding.
3. Failing to recognise that the bleeding is from another source e.g. rectum.
4. Not examining the patient fully and missing obvious clinical diagnoses e.g., PID, foreign body.
5. Not checking a hCG because the patient says there is no way she could be pregnant! Check a hCG… EVERY TIME!
6. Waiting for a urine sample to test for hCG in an unstable patient. Use whole blood on the point of care pregnancy test while awaiting a formal serum hCG.
7. Requesting a pelvic ultrasound on all patients. In most cases this will not change your ED management and is not necessary.
8. Not being familiar enough with the various treatments to discuss them with the patient.
9. Failing to recognise signs of trauma and therefore missing an opportunity to intervene for a vulnerable patient.
10. Failing to treat anaemia caused by the heavy menstrual bleeding.

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