Vaginal Bleeding

Etiology

Vaginal bleeding results from bleeding somewhere in the genital tract, which includes the vulva, vagina, cervix, uterine body, and adnexa. Etiologies include bleeding secondary to gynecologic, obstetric, and systemic processes. Malignancy of any genital organ may result in vaginal bleeding and should be considered.

Gynecologic Etiologies

Uterine causes: In adolescents and adults, vaginal bleeding is frequently caused by abnormal uterine bleeding (AUB). The International Federation of Gynecology and Obstetrics (FIGO) uses the acronym PALM-COEIN to classify AUB, which is a helpful way to conceptually categorize the wide variety of AUB etiologies; the use of this acronym has been adopted by various organizations throughout the world, including the American College of Obstetricians and Gynecologists (ACOG).[1][2][3] Although this classification scheme was developed for reproductive-aged individuals, the same etiologies can also cause bleeding episodes in postmenopausal women. 

The "PALM" etiologies include structural causes of AUB:

• Polyps
• Adenomyosis
• Leiomyomas
• Malignancy or hyperplasia

The "COEIN" etiologies include physiologic or systemic causes:

• Coagulopathy
• Ovulatory dysfunction (typically due to endocrine irregularities or being at the extremes of reproductive age): eg, polycystic ovary syndrome (PCOS), thyroid dysfunction, hyperprolactinemia, within 1 to 3 years of menarche or the menopausal transition
• Endometrial abnormalities: eg, inflammatory or infectious endometritis, disorders of endometrial hemostasis (such as those that occur with endometrial atrophy)
• Iatrogenic causes: eg, hormonal contraceptives, hormone therapy, adverse effects from medication (eg, anticoagulants)
• Not otherwise classified: eg, bleeding from an arteriovenous malformation, uterine sarcoidosis

Additionally, neonates may have withdrawal uterine bleeding during the first week after birth as maternal hormones (present in the neonate's blood) decrease. This bleeding resolves spontaneously and does not require treatment.[4]

Non-uterine Causes

Some of the most common vulvar and vaginal causes of bleeding include trauma, ulcers, neoplasia, atrophy, and erosion due to prolapse, from a foreign body (eg, mesh from prolapse surgery, retained tampon or condom, toilet paper in children) or from radiation therapy. Cervical causes may include infection leading to cervical friability (eg, Chlamydia trachomatis, vaginal candidiasis, bacterial vaginosis), neoplasia, polyps and fibroids, and cervical ectropion. Additionally, endometriosis may cause endometrial implants in the cervix or vagina, leading to irregular bleeding. Although less common, bleeding from the adnexa may also present as vaginal bleeding and may be due to salpingitis, malignancy, and ruptured hemorrhagic cysts.

Obstetric Etiologies

Obstetric causes of vaginal bleeding in the first half of pregnancy include subchorionic hematoma, pregnancy loss, ectopic pregnancy, and gestational trophoblastic disease (GTD).[5] Later in pregnancy, obstetric causes of bleeding include placental abruption, abnormal placentation (eg, placenta previa, vasa previa, placenta accreta spectrum), uterine rupture, and cervical dilation.[6] Of course, non-obstetric causes of bleeding may also cause bleeding in pregnancy and should be considered.

Postpartum hemorrhage is most often due to uterine atony but may also be caused by retained placental fragments or membranes, trauma (eg, cervical or perineal lacerations), uterine inversion, or disseminated intravascular coagulopathy (DIC).[7]

Epidemiology

Any individual with female anatomy (including those with a neovagina) may experience vaginal bleeding, which may occur at any point in their life. When considered a single symptom, "vaginal bleeding" is too broad to identify any epidemiologic patterns; however, patterns are more readily discernible when considering specific etiologies or populations (eg, premenarchal females, pregnant individuals, postmenopausal women).  

For example, the incidence of vaginal bleeding in the first trimester of pregnancy is approximately 25%.[5] The incidence of postmenopausal bleeding is around 5% to 10%, and rates tend to be highest within the first year since the last menstrual period (LMP).[8] 

Etiologies Based on Age

Causes of vaginal bleeding to consider in prepubertal children are vulvovaginitis (most commonly due to retained foreign bodies), trauma (accidental and abuse), urethral prolapse, functioning follicular cysts, estrogen-secreting tumors (eg, ovarian granulosa cell tumors), McCune-Albright syndrome, and inadvertent exogenous estrogen exposure.

For individuals in the reproductive-aged group, the most commonly identified causes of AUB include ovulatory dysfunction and leiomyomas. Those with AUB due to malignancy tend to be older relative to others in the reproductive-aged group.[9][10]

Rates of malignancy are overall highest in the postmenopausal-aged group; therefore, cancer must always be ruled out when patients present with vaginal bleeding in this age group.

History and Physical

History

The history should be used to assess the stability of the patient and whether the bleeding is acute or chronic. The menstrual status and anatomy of the patient should be determined. For example, the patient may be characterized as a premenarchal child, postmenarchal adolescent, reproductive-aged female with typical anatomy and regular menstrual cycles, peri- or postmenopausal adult, gender diverse individual, an individual with a prior hysterectomy, etc. If menstruating, the date of the LMP should be determined. This information will help focus the differential diagnosis. A review of contraceptive methods used by the patient and their partner(s) should be obtained, and the individual should be asked if they believe they are or could be pregnant (though in patients of reproductive age, pregnancy status should always be confirmed with a pregnancy test). 

Next, it is important to characterize the onset, frequency, duration, and severity of the bleeding. The volume of bleeding can be assessed by asking about the saturation level of menstrual products and how often they are changed. Precipitating factors should be identified; it is prudent to ask about any known traumatic events, any recent changes in exogenous hormone use (such as a new hormonal contraceptive or change in dosing), and if bleeding primarily occurs after contact (eg, after intercourse or a pelvic exam) which would suggest cervical friability or an unstable endometrium (polyps can also present this way). Additionally, the clinician should inquire about associated symptoms that may point to specific etiologies. Frequently, this would include asking the patient about the following:

• Pelvic pressure, dyspareunia, constipation, or urinary frequency (may suggest a mass)
• Dysmenorrhea (suggests leiomyoma or adenomyosis)
• Unintentional weight loss (may suggest malignancy or hyperthyroidism)
• Galactorrhea (which may indicate hyperprolactinemia) or hirsutism (which may indicate hyperandrogenism, PCOS, or congenital adrenal hyperplasia)
• Heavy bleeding since menarche, a history of surgical, dental, or obstetric bleeding, frequent bruising, epistaxis, or a family history of bleeding symptoms (may suggest a coagulopathy)[3]
• Pelvic pain, abnormal or foul-smelling vaginal discharge, or vaginal pruritus (suggests infection)

Beyond the first trimester of pregnancy, ask whether the bleeding is associated with pain or contractions (painful bleeding points to abruption, uterine rupture, or labor while painless bleeding suggests placenta or vasa previa), a loss of fluid, or a decrease in fetal movement. If the patient is recently postpartum or had a miscarriage (within the past few weeks or months), it is also essential to learn about the birth or loss; for example, manual extraction of the placenta may suggest retained placental fragments, while prolonged bleeding after a miscarriage may suggest retained products of conception or GTD.

In all patients, inquire about potential symptoms of anemia due to heavy and/or recurrent bleeding (eg, pallor, dizziness, fatigue). Additionally, risk factors for gynecologic malignancy (eg, chronic unopposed estrogen exposure, family history, cervical cancer screening history, etc) should be reviewed. Medications should be carefully reviewed to determine if any may affect bleeding. Finally, a full obstetric, gynecologic, medical, surgical, and family history should be obtained, which may reveal factors that impact evaluation and management.

Examination

The examination should be used to:

• Assess the stability of the patient
• Attempt to visibly identify (and address) the source of bleeding
• Look for and address any signs of trauma or foreign bodies
• Look for signs of infection (eg, abnormal discharge, ulcers, increased pelvic tenderness) and obtain samples as indicated
• Look for signs of neoplasms (eg, visible lesions, palpable mass) and take biopsies, as indicated
• Look for signs of endocrinopathies (eg, enlarged thyroid, hirsutism)

In pregnant patients, the exam should also assess cervical dilation, membrane status, and fetal heart rate. Note: A cervical exam should never be performed in a pregnant patient until the provider has confirmed on ultrasound that neither the placenta nor placental vessels overlie the internal cervical os; digital exams may cause serious injury. In patients who are immediately postpartum, manual exploration of the uterine cavity may identify (and allow the provider to remove) retained placental fragments.

Premenarchal Children

Depending on the age of the child, the history and exam should also include the maternal age of first menses, any history of potential trauma (including abuse) in the child, endocrine symptoms (eg, weight loss, polyuria), and other signs of early puberty (eg, breast bud development, presence of pubic hair) which typically occur prior to the onset of menses.

An external exam of the introitus is important to look for signs of trauma, masses, and foreign bodies (eg, toilet paper). This can usually be accomplished with the child in a "knee-chest" position rather than traditional lithotomy. In children, a speculum exam is usually not indicated, but if absolutely required, typically should be done under anesthesia. 

Postmenopausal Adults

After the menopause transition, malignancy is much higher on the differential and must always be ruled out. Therefore, the history and physical should focus on other signs and symptoms that may suggest a neoplasm, such as weight loss, easy bruising, a palpable mass, or a visible lesion. Vaginal atrophy is also usually present to some extent unless the patient is using hormone therapy, so care should be taken during a speculum exam, which is more likely to be uncomfortable/painful in this population. 

Transgender and Gender Diverse Individuals

At the beginning of the encounter, patients should be asked about their preferred name, pronouns, and language used to describe their body parts.[11] When a gender diverse patient presents with vaginal bleeding, it is important to clarify what organs the patient has and review any hormonal medications they may be taking. Like with any adult presenting with vaginal bleeding, a speculum exam is typically indicated; however, sensitivity and clinical judgment should be used, as gender diverse individuals may have more anxiety and fear surrounding this procedure, especially if they do not identify as a woman. Additionally, testosterone can cause vaginal atrophy, making a speculum exam more physically painful.

Evaluation

The evaluation of vaginal bleeding varies based on the patient's age and reproductive status. In all patients with bleeding, the volume of blood loss should be estimated from the history (eg, pad counts). A complete blood count (CBC), coagulation panel, and type and cross match are typically indicated if bleeding is heavy. 

Evaluation of Reproductive-Aged Patients

The first step in evaluating any person with vaginal bleeding and reproductive potential is to obtain a pregnancy test (unless the person is already known to be pregnant).

Workup if the Pregnancy Test is Newly Positive: In the first half of pregnancy, obstetric bleeding may be due to ectopic pregnancy, pregnancy loss, a subchorionic hematoma, or GTD (in addition to non-obstetric causes of bleeding). Therefore, if a pregnancy test is positive (in addition to ruling out non-obstetric causes of bleeding with a history and exam), the first steps are to determine:

1. Location of the pregnancy
2. Viability of the pregnancy
3. Approximate gestational age

In early pregnancy, all 3 of these goals can typically be achieved with a pelvic ultrasound, and if an intrauterine pregnancy is not clearly identified on ultrasound, a quantitative serum beta-human chorionic gonadotropin (hCG) level should be obtained; sometimes, the hCG level needs to be trended over time to make the correct diagnosis. The hCG level is typically unnecessary if a bedside ultrasound clearly demonstrates an intrauterine embryo/fetus with visible fetal cardiac activity (FCA). If, however, FCA has not yet been detected, a serum hCG level is indicated. Since an hCG level can help radiologists interpret ultrasound findings before the development of FCA, it is usually prudent to obtain the hCG level before ordering a formal pelvic ultrasound. (Note: hCG levels rise at known rates early in pregnancy, but this rising slows as the embryo/fetus grows and ultimately plateaus around 10 weeks of gestation, which is why hCG levels are less relevant later in the first trimester.)[12]

Determining pregnancy location: Ectopic pregnancy must always be ruled out in early pregnancy. Unless a patient has risk factors for a heterotopic pregnancy (eg, use of assisted reproductive technologies), visualization of a yolk sac and/or embryo/fetus establishes the pregnancy location; if these structures are seen within the uterus, ectopic pregnancy is effectively ruled out. If ultrasound cannot definitively identify the location of the pregnancy, serial hCG levels and ultrasounds should be obtained every 48 to 72 hours until the location is confirmed or hCG levels fall to non-pregnant levels.[12] (A full discussion regarding the evaluation of a potential ectopic pregnancy is discussed elsewhere.)[13]

Assessing fetal viability: The presence of FCA confirms viability. If the cervical os remains closed, the pregnancy may (or may not) progress to a live birth, even in the setting of vaginal bleeding, though heavier bleeding increases the risk of pregnancy loss. Pregnancy loss is inevitable if the internal cervical os is open on exam and/or ultrasound. Once a fetal pole with FCA is visible on ultrasound, an hCG level typically is not needed, and viability can be followed with serial ultrasounds.[5] Prior to the visualization of FCA, specific ultrasound criteria can be used to diagnose early pregnancy failure.[14] (These criteria are discussed in detail elsewhere.)[15]

Establishing the gestational age: The gestational age can be determined by calculating the estimated due date (EDD) from the LMP and sonographic measurements of specific biometric parameters. If the EDD from the LMP matches the EDD determined by ultrasound measurements, the LMP-derived EDD is typically used. If there is a significant discrepancy, the ultrasound-derived EDD is used. ACOG provides specific criteria and cutoff values to standardize EDD determinations.[16]

GTD tumors arise from abnormal fertilization events and include molar pregnancies and potentially malignant conditions, including invasive mole, choriocarcinoma, and several trophoblastic tumors.[17] Molar pregnancies are diagnosed primarily by ultrasound, which shows characteristic findings, such as a heterogenous mass with a vesicular pattern indicating hydropic villi replacing the placenta. In patients with a complete mole, theca lutein cysts may also be visualized on ultrasound, and hCG levels are often abnormally high, usually >100 000 mIU/mL (though these elevated levels are only rarely seen in partial moles). Gestational trophoblastic neoplasias (GTN) are malignant processes originating from abnormal trophoblastic tissue that can be identified with persistently elevated hCG following a pregnancy event (eg, miscarriage, delivery of a viable pregnancy, molar pregnancy, etc) after ruling out a new pregnancy.[17]

Workup in the Second Half of Pregnancy: In the second half of pregnancy, the evaluation is guided by the potential causes of bleeding, which include placental abruption, placenta or vasa previa, uterine rupture, labor, and non-obstetric causes of bleeding. For these pregnant patients past the point of viability, fetal well-being must be assessed. This is typically accomplished with a non-stress test (NST) and obstetric ultrasound. The ultrasound should also assess the placenta and any known uterine scars. After ultrasound confirms that neither the placenta nor any vessels are within close proximity to the internal cervical os, a physical exam should be performed to assess the cervix, membrane status, and volume of bleeding. If bleeding is significant and/or a patient has sustained major trauma, a Kleihauer-Betke test can be performed, which can identify feto-maternal hemorrhage; if positive, Rh D immune globulin is typically indicated in Rh-negative patients to prevent alloimmunization.[18]

Placental abruption is a clinical diagnosis typically characterized by the sudden onset of painful bleeding, high-frequency, low-amplitude uterine contractions, and fetal distress.[19] The abruption may or may not be visible on ultrasound, but a fluid collection noted behind the placenta is a highly specific finding.[20] Bleeding from a placenta previa (placenta covering the internal cervical os) is typically painless, and this abnormal placenta location can be identified on ultrasound. Uterine rupture often presents with a sudden onset of painful bleeding in a patient with a prior uterine incision, fetal distress (often bradycardia), a tetanic uterine contraction or increased contractions, and loss of fetal station.[21] 

Workup in the Puerperium: Postpartum hemorrhage is also diagnosed clinically based on estimates of blood loss and physical exam findings (eg, uterine atony, obstetric lacerations). A CBC, coagulation panel, and type and cross-match are all indicated if bleeding does not rapidly resolve with uterotonic agents. If lochia is heavier than expected or prolonged, an ultrasound may be indicated to look for evidence of retained products of conception. A persistently elevated hCG level suggests GTD.

Workup in Nonpregnant Patients: The evaluation of vaginal bleeding in nonpregnant patients in the reproductive-aged group should be guided by history and examination findings. Keeping the PALM-COIEN acronym in mind for potential etiologies of AUB, the patient should be evaluated for common structural and non-structural causes of uterine bleeding. This workup usually includes a pelvic ultrasound, bloodwork, and potentially endometrial tissue sampling to rule out hyperplasia. Endometrial sampling may also suggest other chronic endometrial etiologies.

A pelvic ultrasound should be the first diagnostic test of choice when evaluating a patient for possible structural uterine anomalies, such as leiomyomas or adenomyosis. Other potential studies that can evaluate structural causes of AUB include hysteroscopy or a saline-infusion sonogram, which are better modalities for identifying uterine polyps and other intracavitary pathology. Operative hysteroscopy allows the practitioner to obtain targeted biopsies and provide concurrent treatment of polyps and intracavitary fibroids. Additionally, a pelvic magnetic resonance imaging (MRI) study can help further characterize the pelvic organs (most commonly in patients with a fibroid uterus or complex adnexal mass) if additional imaging is needed (eg, for surgical planning of myomectomy, concern for malignancy, etc).

Evaluation of the endometrium is required in all patients with risk factors for malignancy, for example, those older than 45 years of age or younger patients with obesity or a significant history of unopposed estrogen exposure (eg, frequent anovulatory cycles in PCOS).[3] Endometrial evaluation is typically accomplished in the office with an endometrial biopsy or surgically, with a dilation and curettage.

Testing for coagulopathies should be considered in all patients with acute uterine bleeding or in those with a history of heavy menstrual bleeding (HMB) since menses began, especially in adolescents.[22] For adolescents requiring hospitalization due to AUB, nearly 1 in 5 may have an underlying coagulopathy.[3] Initial testing should include a CBC and coagulation panel. Those with abnormalities on these initial screening tests and those with risk factors for coagulopathy identified on history should have additional testing.[3]  This includes testing for specific coagulopathies (eg, von Willebrand disease, hemophilia), an iron panel, and liver function tests. 

The workup for AUB in reproductive-aged patients also typically includes an evaluation for thyroid disorders, which can cause irregular bleeding. In addition to a thyroid stimulating hormone (TSH) level, additional testing may be indicated based on history and exam findings. For example, a prolactin level and/or hemoglobin A1c may be ordered to rule out hyperprolactinemia in the setting of abnormal nipple discharge or diabetes mellitus in the setting of polyuria, respectively. 

Non-uterine causes of bleeding should also be considered. In addition to a careful pelvic exam, cervical cancer screening should be performed if the patient is not current with screening or if concerning symptoms are present (eg, contact bleeding and the presence of external genital warts). Suspicious lesions of the vulva, vagina, or cervix can be assessed with colposcopy and biopsied if clinically appropriate. Testing for sexually transmitted infections (STI), especially Chlamydia trachomatis, that may cause cervicitis should also be offered to patients. 

Evaluation in Premenarchal Children

In premenarchal children, any additional testing is based on the suspected etiology after the history and physical exam. This may include, for example, testing for STIs (if abuse is suspected), endocrinopathies (eg, diabetes, thyroid disorders), coagulopathies, and/or an exam under anesthesia.

Evaluation in Postmenopausal Patients

Although the cause of postmenopausal bleeding is most often benign (eg, endometrial atrophy, benign polyps), malignancy must always be ruled out in postmenopausal people with vaginal bleeding because up to 14% of cases may be due to endometrial cancer (depending on age and risk factors).[23]

The endometrium is best evaluated with a transvaginal ultrasound and/or tissue sampling. Transvaginal sonography is a reasonable first-line test because evidence suggests that cancer is extremely unlikely when a transvaginal ultrasound shows a very thin endometrial stripe: an endometrial stripe of ≤4 mm has a negative predictive value of >99% for endometrial cancer.[23] Although a thickened endometrial stripe has a poor positive predictive value, if the endometrial stripe is at least 5 mm, endometrial tissue sampling is warranted. Alternatively, many practitioners perform endometrial sampling in all postmenopausal patients with vaginal bleeding as a first-line test, and this is also a reasonable approach.

Cervical cancer testing should also be performed, and abnormal visible lesions should be biopsied (even with normal cytology). Additionally, bleeding due to infections (including STIs) should also be considered in this population.

Treatment / Management

The management of acute vaginal bleeding will be dictated by the underlying etiology.

In cases of significant bleeding, the provider should initially focus on stabilizing the patient, focusing on the airway, breathing, and circulation (the "ABCs"). If the patient is having uncontrolled bleeding, the provider may need to pack the vagina to slow blood loss. Blood transfusions may also be indicated.[24][25](A1)

Iron deficiency anemia from blood loss should be treated with iron supplementation until resolved. Beyond this, treatments will vary based on the result of the evaluation. 

Acute, Heavy AUB in Nonpregnant Adolescents and Adults

Heavy, acute uterine bleeding in nonpregnant patients may be significant but is usually treated medically, with hormone therapy as the first-line approach, reserving surgical management for more specific indications (see below). Some medical options include IV conjugated equine estrogen, oral progestins, combination oral contraceptive pills (OCPs), and tranexamic acid.[22] The 2013 ACOG Committee Opinion on the management of acute AUB in nonpregnant reproductive-aged people includes the following potential regimens to staunch the flow of heavy acute uterine bleeding:(B3)

• Conjugated equine estrogen 25 mg IV every 4 to 6 hours for 24 hours[26]
• Combination OCPs: a monophasic preparation containing at least 35 mcg of ethinyl estradiol, 1 tab PO three times daily for 7 days[27] (Note: Many clinicians will instead give some variation of an OCP taper, though none have any substantial evidence behind them. One example regimen is 1 pill 3 times daily for 3 days, then twice daily for 2 days, then once daily to finish the pack; another example is 5 pills on day 1, 4 pills on day 2, 3 pills on day 3, 2 pills on day 4 and 1 pill on day 5.)
• Medroxyprogesterone acetate 20 mg PO three times daily for 7 days[27]
• Tranexamic acid (TXA) 1.3 g PO  three times daily for 5 days (or 10 mg/kg IV up to a maximum of 600 mg/dose)[28]
(A1)

If a bleeding disorder is known or suspected, consultation with a hematologist is recommended. If bleeding is not controlled with the above regimens in patients with a coagulopathy, potential options may include desmopressin, recombinant factor VIII, von Willebrand factor, or factor-specific replacement.[22]  Nonsteroidal anti-inflammatory drugs (NSAIDs) are typically avoided in these patients.(B3)

Surgical management may be indicated in some patients, typically including those with hemodynamic instability, severe and/or uncontrolled bleeding, contraindications to medical management (eg, breast cancer, history of thromboembolic events, severe liver disease, etc), or those who fail medical management. Options include dilation and curettage (D&C), potentially with concurrent hysteroscopy, and, for patients who no longer desire future fertility, endometrial ablation, uterine artery embolization (UAE), or hysterectomy.[22] Uterine tamponade (typically with a balloon catheter filled to at least 30 mL or a long, continuous piece of gauze) may also be used for up to 24 hours, either while waiting for surgery or in addition to a D&C in patients who continue bleeding but desire future fertility.(B3)

Once the acute episode of bleeding is controlled, the underlying etiology should be addressed to prevent future episodes. The same medical and surgical treatments used for chronic AUB may be offered. For example, a patient may be continued on OCPs, a levonorgestrel-releasing intrauterine device (LNG-IUD) may be placed, or elective surgery may be scheduled to remove a fibroid or polyp (if not already done). Malignancies are treated with a variety of surgical, chemo- and radiation therapies.

Mild Acute AUB or Chronic AUB in Nonpregnant Adolescents and Adults

Management options in reproductive-aged people vary somewhat depending on the etiology. Adenomyosis and many of the "COEIN" etiologies are typically managed with hormone therapy, including some type of hormonal contraceptive (OCPs, patch, vaginal ring), TXA during menses, or a LNG-IUD. Endometrial ablation, UAE, and hysterectomy are also surgical options for those who have completed childbearing and desire definitive management. Chronic endometritis can be treated with a course of doxycycline. Polyps are typically removed hysteroscopically. Small leiomyomas may be managed medically with hormone therapy, TXA, or an LNG-IUD; larger fibroids, however, which cause both bleeding and bulk-related symptoms, often require surgical management with either a UAE, myomectomy, or hysterectomy. GnRH antagonists (such as elagolix and relugolix, often formulated with low-dose "add-back" therapy) and agonists (such as leuprolide) can also be options to help shrink a fibroid before definitive surgical management or function as a bridge to natural menopause when fibroids naturally shrink. Malignancies are managed according to histologic type, stage, and grade and may involve surgery, chemotherapy, radiation, and/or hormonal therapy.

Acute Non-Uterine Vaginal Bleeding in Nonpregnant Children, Adolescents, and Adults

In these patients, the underlying etiology will guide treatment. For example, traumatic lacerations may require suturing. Bleeding from infectious cervicitis should resolve with appropriate antimicrobial therapy. Cervical dysplasia or malignancy typically requires excision and/or radiation. Erosions from mesh used during an incontinence procedure are often treated topically with vaginal estrogen.

Obstetric Bleeding

Ectopic pregnancy is treated with either methotrexate or surgical excision, though rarely, if clinical factors suggest that the pregnancy is spontaneously resolving (eg, low and decreasing hCG levels) in a patient with easy access to medical care, expectant management may be appropriate. Patients treated medically with methotrexate or expectantly require hCG levels followed to nonpregnant levels because trophoblastic tissue may persist, and rupture of ectopic pregnancies at extremely low or decreasing hCG levels has been reported.[12]

Miscarriage may be treated with expectant, medical, or surgical approaches. Medical management typically involves misoprostol, while surgical management consists of uterine evacuation via uterine aspiration or a suction D&C. Expectant management is often successful but may take up to 8 weeks to complete.[29]

Acute bleeding later in pregnancy with a viable fetus may require an emergent cesarean delivery to stop maternal and fetal hemorrhage, including in patients with a significant placental abruption or uterine rupture (considered true obstetric emergencies). Bleeding due to smaller abruptions, placenta previa, or cervical dilation is managed individually based on a variety of factors, including the gestational age, amount of bleeding, membrane status, the presence or absence of uterine contractions, the presence or absence of infection, fetal well-being, etc. Generally, corticosteroids are indicated to promote fetal lung maturity in patients prior to 37 weeks of gestation.[30] The need for prophylaxis against group B Streptococcus (GBS) should also be determined.[31] (B3)

Postpartum hemorrhage should be treated with uterotonic agents, including oxytocin, methylergonovine, 15-methyl prostaglandin F_2α, and/or misoprostol.[7] Lacerations (including cervical lacerations) should be sutured. Bimanual uterine massage can help stimulate an atonic uterus to contract while uterotonic agents are administered. This is done by placing one hand inside the vagina, beneath the cervix, and the other hand on the abdomen; the uterus is then compressed and massaged between the two hands. If this is unsuccessful, a uterine tamponade balloon or thrombin-soaked gauze can be placed in the uterus, applying compressive pressure within the uterus. If bleeding persists, surgery is indicated; procedures include vascular ligation, uterine compression sutures, and hysterectomy.[7]

Rh D immune globulin can prevent the development of Rh D antibodies from forming in Rh-negative patients exposed to Rh-positive fetal blood. While international guidelines vary; generally, Rh D immune globulin should be given to Rh-negative people after a potentially sensitizing event.[32][33] This issue is discussed further elsewhere.[34]

GTD is treated with uterine evacuation and chemotherapy if gestational trophoblastic neoplasm (GTN) is present. Fortunately, even patients with metastatic disease have a good prognosis, as GTN is highly sensitive to chemotherapy. Serum hCG levels must be followed closely in these patients. Hysterectomy should also be considered in some patients with GTN who no longer desire future fertility.[17]

Differential Diagnosis

Causes of Vaginal Bleeding in Adolescents and Adults

Structural uterine causes of bleeding ("PALM"): polyps, adenomyosis, leiomyomas, malignancy, or hyperplasia

Non-structural uterine causes of bleeding ("COEIN"): coagulopathy, ovulatory dysfunction (due to endocrinopathies such as thyroid disorders or the extremes of reproductive age), iatrogenic, endometrial dysfunction (including endometritis and hemostatic dysfunction due to estrogen-deficient atrophy), and not yet classified

Vulvovaginal causes of bleeding in nonpregnant patients: trauma, infection (eg, bleeding condyloma acuminata), ulcers (eg, herpes simplex virus, Behçet disease), neoplasia, atrophy, erosion due to a foreign body or prolapse, vaginal endometriosis

Cervical causes of bleeding in nonpregnant patients: infectious cervicitis, neoplasia, polyps, fibroids, ectropion

Adnexal causes of bleeding in nonpregnant patients: neoplasia, ruptured hemorrhagic cysts, salpingitis[1][2][3][2][1]

Obstetric causes of bleeding: ectopic pregnancy, early pregnancy loss, subchorionic hematoma/hemorrhage, GTD/GTN, placental abruption, placenta previa, uterine rupture, cervical dilation/labor, postpartum uterine atony, retained placenta, and obstetric lacerations[2][3][2]

Causes of Vaginal Bleeding in Children 

The differential diagnosis of vaginal bleeding in children includes vulvovaginitis (most often due to retained foreign bodies such as toilet paper), trauma (accidental and abuse), urethral prolapse, estrogen-secreting tumors (eg, ovarian granulosa cell tumors), and inadvertent exogenous estrogen exposure. In neonates, within the first week of life, bleeding is frequently a "withdrawal bleed" as maternal hormone levels drop in the infant's serum.

Prognosis

The prognosis of vaginal bleeding is very good for many etiologies, though this can vary significantly. Heavier bleeding, especially bleeding resulting in hemodynamic instability and malignancies, will have less favorable prognoses compared to lighter bleeding from a benign cause. 

Gestational age and severity of bleeding are also critical factors for determining the neonatal prognosis in pregnant patients. For example, the neonatal prognosis will be significantly better for a patient at 38 weeks of gestation with light bleeding due to a small partial abruption at the edge of the placenta compared with the prognosis for a patient requiring an emergent cesarean delivery at 28 weeks due to a severe placental abruption with heavy bleeding after vehicular trauma. 

Complications

Complications of acute vaginal bleeding in nonpregnant patients occur due to acute blood loss, for example, anemia, acute kidney injury, hemodynamic instability, transfusion reactions, and complications of emergency surgery (eg, organ injury, infection, loss of fertility).

Higher doses of hormone therapy, commonly used in the medical treatment of acute uterine bleeding, increase the risk of thromboembolic events.

Obstetric complications for bleeding in the second half of pregnancy include preterm delivery, cesarean delivery, postpartum hemorrhage, and adverse fetal/neonatal outcomes related to prematurity, blood loss, and poor oxygenation in utero.

Ruptured ectopic pregnancy can lead to significant internal hemorrhage and maternal death if not promptly treated.