Vaginal bleeding is a common complaint with a broad differential diagnosis. This article deals primarily with the general approach to vaginal bleeding, the appropriate workup, and treatment strategies.
The etiology of vaginal bleeding can vary widely, from infectious to endocrine to malignant to anatomical to physiological causes. Vaginal bleeding can be grouped broadly into bleeding secondary to gynecologic processes and bleeding secondary to systemic processes. Gynecologic procedures can be divided further into bleeding secondary to anatomic disruption and bleeding secondary to physiological disruption. Systemic processes can be divided into bleeding secondary to an endocrine etiology and bleeding secondary to a hematologic/oncologic etiology. The likelihood a given process is responsible for vaginal bleeding in an individual depends on their age and pregnancy status.
Any woman can have vaginal bleeding. It is helpful to think of vaginal bleeding in terms of whether the patient's vaginal bleeding is normal (in other words, a woman of childbearing age) versus abnormal (pre-menarchal children and post-menopausal women). For patients of childbearing age with vaginal bleeding, it is critically important to determine the patient's pregnancy status, as the differential diagnosis and workup of the pregnant patient with bleeding are different from that of the non-pregnant one.
In the non-pregnant woman of childbearing age, vaginal bleeding occurs cyclically every 28 days or so. This process is tightly regulated by interactions between the hypothalamus, the pituitary, and the ovary. Day 1 of the menstrual cycle is defined as the first day of menstrual bleeding. This marks the beginning of the follicular phase of the menstrual cycle, during which estrogen and progesterone levels are low. Through the follicular phase, follicle-stimulating hormone (FSH) levels increase gradually, as do estrogen levels. Rising estrogen stimulates the endometrium to becomes thicker, with increasing numbers of endometrial glands. Estrogen peaks in the late follicular phase, followed by an LH surge, which marks the beginning of the luteal phase. Estrogen peaks in the late follicular phase, followed by an LH surge, which marks the beginning of the luteal phase. This results in ovulation. The remaining corpus luteum secretes progesterone, while estrogen levels fall. This results in loss of endometrial blood supply, causing sloughing of the endometrial lining and the beginning of a new cycle. This bleeding typically lasts 3 to 7 days, and about 75 cc of blood are lost.
Abnormal Bleeding in non-pregnant women of childbearing age
In non-pregnant women of childbearing age, abnormal vaginal bleeding may be cyclical or non-cyclical. Heavy cyclical bleeding, or menorrhagia, implies an intact hypothalamus-pituitary-ovarian axis. Menorrhagia is most commonly secondary to systemic endocrine processes (hypothyroidism), systemic hematological/oncological processes (e.g., Von Willibrand's disease, or other bleeding diathesis), or anatomical disruptions, such as polyps, fibroids, or trauma. The bleeding in menorrhagia can be severe and result in symptomatic anemia. Non-cyclical bleeding, or menometrorrhagia, is irregular bleeding at often prolonged intervals. Menometrorrhagia implies derangement of the hypothalamic-pituitary-ovarian axis and typically involves a failure of ovulation to take place, so it is often called anovulatory bleeding. Patients with menometrorrhagia may have the same underlying pathologies as those with menorrhagia, but also may have other systemic endocrine processes such as diabetes, polycystic ovarian syndrome, or hyperprolactinemia, may have anovulation secondary to obesity or an eating disorder, might have ovulatory failure from certain medications such as psychiatric medications, may have underlying malignancies, or may simply be at the extremes of their menstrual ages (adolescence or menopause). Bleeding with menometrorrhagia is typically not very heavy, but the lack of cyclical withdrawal bleeding places these patients at increased lifetime risk for endometrial cancer.
Bleeding in pregnancy
Although bleeding in pregnancy is not considered "normal," it is common, affecting about one in three pregnancies. In the first trimester, common causes of bleeding are normal implantation of a fertilized ovum into the endometrial lining, spontaneous miscarriage, ectopic pregnancy, and subchorionic hemorrhage. In the second trimester, bleeding may be related to placenta previa, placenta accreta, placental abruption, or intrauterine fetal demise/spontaneous miscarriage. In the third trimester, bleeding is concerning for placental abruption, placenta previa, or labor. Each of these pathologies has its entry discussing its presentation and pathophysiology.
Bleeding in premenarchal children
Bleeding in children is most commonly related to anatomical disruptions. In female neonates, vaginal bleeding sometimes occurs as the pediatric endometrium withdraws from the stimulus of mom's hyperestrogenic state, and in older children, sometimes endocrine processes may lead to precocious puberty and vaginal bleeding. Most commonly, though, vaginal bleeding is related to trauma (for instance, straddle injuries), polyps or tumors (sarcoma botryoides), infection/inflammation/vaginitis, or foreign body (usually toilet paper).
Bleeding in post-menopausal women
Although women may have menometrorrhagia as they near menopause, abnormal bleeding may also be secondary to simple atrophy (atrophic vaginitis). Other causes are similar to other groups of women, including anatomical processes (polyps, infections, foreign body), endocrine processes (e.g., thyroid disease), bleeding dyscrasias (including those related to malignancies and medications) and gynecologic malignancies. The most common presentation of endometrial cancer is abnormal vaginal bleeding, and therefore consideration must be given to this entity when evaluating the patient with abnormal vaginal bleeding.
The first step in assessing someone with vaginal bleeding or indeed any bleeding is to determine if the patient is stable. Vaginal bleeding can be copious, and the medical provider should elicit history for a worrisome amount of bleeding (bleeding for greater than 7 days, bleeding through pads/tampons, the passage of clots larger than 3 cm in diameter, and symptoms of anemia). The provider should be cognizant that significant amount of blood may be lost with no change in vital signs, and so exam should carefully assess for pallor, orthostasis, or mild dyspnea. In patients with abnormal vital signs, significant hemorrhage should be presumed to be present.
In premenarchal children, history should include the maternal history of first menses, child's history of potential trauma (including abuse), endocrine symptoms (weight loss, polyuria), and history of other signs of early puberty. In children, speculum exam is not appropriate, but exam of the introitus is important to look for signs of trauma, masses, and foreign bodies. In some cases, the child may require exam under anesthesia.
In post-menopausal women, history should focus on other symptoms concerning for malignancy (weight loss, easy bruising) or endocrine disease. A physical exam will often show signs of atrophy, but may also give evidence of trauma or infection. Physical examination is not adequate to exclude endometrial malignancy in post-menopausal women.
In women of reproductive age, the provider should obtain a sexual and menstrual history, and attempt to determine if the bleeding is cyclical (menorrhagia) or non-cyclical (menometrorrhagia). Full pelvic exam, including speculum exam and bimanual exam, is appropriate.
In premenarchal children, there is often no specific evaluation that needs to take place beyond thorough history and physical exam. Depending on suspicion for other etiologies, diabetes screening, thyroid studies, bleeding studies, hemoglobin/platelets, and exam under anesthesia may be warranted.
In postmenopausal women who are hemodynamically stable, blood work should only be ordered as indicated or suggested by history and exam. However, postmenopausal women with vaginal bleeding should undergo a transvaginal ultrasound and be referred for an endometrial biopsy to assess for endometrial cancer.
A pregnancy test should always be performed in women of childbearing age, regardless of their history of sexual activity. In stable non-pregnant women with menorrhagia, there is no indication for other tests in the emergency department setting; however, outpatient workup can be extensive. Outpatient studies often consist of tests to assess for anemia and blood dyscrasias (ferritin, coagulation studies, complete blood count, and bleeding studies), tests to assess for thyroid disease (TSH and free T4), tests to assess for liver disease, and even advanced procedures (hysteroscopy) to look for anatomical causes of bleeding.
In stable non-pregnant women with menometrorrhagia, although there is no absolute indication for emergency blood tests, outpatient workup often includes a complete blood count, fasting glucose, HgAIC, ultrasound (to assess for polycystic ovaries), FSH/LH, thyroid studies, prolactin level, and even endometrial biopsy.
In women with vaginal bleeding in the first trimester of pregnancy, a transvaginal ultrasound should be performed to determine the location of the pregnancy to rule out ectopic pregnancy. A blood type should also be performed to determine the need for RhoGAM administration. In later trimesters of pregnancy, transabdominal ultrasound to determine the location of the placenta is important. These patients should be admitted to obstetrics for cardiotocographic monitoring.
In cases of significant bleeding, the provider should focus on stabilizing the patient, with attention to the ABCs. If the patient is having uncontrolled bleeding, the provider may need to pack the vagina to slow blood loss. Transfusion of red blood cells should be performed in patients with significant symptoms.
Beyond this, treatment depends on the etiology of the patient's vaginal bleeding. In cases of mild vaginal bleeding, often no specific therapy is required urgently, and work-up for underlying etiology and treatment of that etiology becomes paramount.
In cases of menorrhagia where bleeding can be heavy over time, and if no underlying cause can be identified and treated, the focus of treatment is to reduce the amount of blood loss. This reduction may be accomplished in a variety of ways. Use of non-steroidal anti-inflammatory medications on the first 5 days of the menstrual cycle reduces bleeding by 30%. Oral tranexamic acid taken on the first five days of the cycle or use of a combined or progesterone oral contraceptive pill reduces bleeding by about half, Use of a progesterone eluting intrauterine device reduces bleeding by 97%. Patients should also be provided with an iron replacement.
In patients with menometrorrhagia in whom an underlying source cannot be identified and treated, the provider's main concern is with reducing the patient's cancer risk. Patients with menometrorrhagia usually have infrequent bleeding and are less likely to have symptomatic anemia. Oral medroxyprogesterone for 10 to 14 days (to stimulate a withdrawal bleed and complete sloughing of the endometrium), low dose estrogen combined oral contraceptive pills, or placement of an intrauterine progesterone device all reduce the patient's risk of endometrial cancer.
Patients may have significant vaginal bleeding in the post-partum setting as well. Risk factors for postpartum hemorrhage include multiparity, multiple gestations, prolonged labor, prior history of bleeding, and use of medications known to cause bleeding.
In assessing these patients, the provider should determine if the bleeding is secondary to problems with uterine tone (the uterus being inverted or not contracting) and should treat these patients with bimanual uterine massage, oxytocin, misoprostol, and or ergotamines. If the bleeding does not appear to be related to tone, the provider should look signs of trauma and repair any lacerations or tears. The provider should consider tissue as a source, and manually remove any retained placenta. Finally, the provider should consider the possibility of thrombin dysfunction, disseminated intravascular coagulopathy, or underlying bleeding diathesis, which may require treatment with fresh frozen plasma or platelet infusion.