Ronan A. Bakker
History of present illness
A 28-year-old obese gravida 0 woman presents to the emer- gency department complaining of general malaise, weakness, lightheadedness, and heavy vaginal bleeding. She had a single episode of “blacking out”earlier in the day, which led her to seek medical care. The bleeding has been“as much as a regular period” if not heavier for the last eight days. She has been passing golf-ball-size clots and has been changing pads every one to two hours. She reports the pads are completely“soaked through.”For the last seven days, the patient has felt worsening weakness, lightheadedness and shortness of breath culminating in a syncopal episode earlier today. She has cramping abdom- inal pain which is tolerable and not severe in nature (3 out of 10 on the pain scale).
Her “periods” have been irregular since graduating from college, occurring every two to three months. In the last two years she has begun to have worsening intermenstr- ual bleeding and the bleeding episodes have become heavier and longer in duration. They usually last for five to eight days.
She has had scant medical care. She denies a history of sexually transmitted infections. She has never been trans- fused, but has been on iron supplementation in the past for anemia. She takes no prescription medications and does not take the iron on a consistent basis. She denies a history of nose bleeds, easy bruising, or bleeding gums. She has not had any prior surgery and has no other known medical problems.
Physical examination
General appearance: Woman appearing tired and pale Vital signs:
Temperature 37.3°C Heart rate: 125 beats/min Blood pressure: 95/45 mmHg Respiratory rate: 24 breaths/min Oxygen saturation: 97% on room air BMI: 38 m/kg2
HEENT: Hirsutism and acne noted on face
Cardiovascular: Tachycardia; no murmurs, rubs, or gallops
Respiratory: Clear to auscultation bilaterally
Abdominal: Mild bilateral lower abdominal discomfort, normal bowel sounds, no distention
Pelvic:
Speculum exam: Three scopettes of blood removed from vaginal vault and several quarter-size clots noted.
Moderate amount of blood noted to be coming from cervical os. Cervix appears normal
Bimanual exam: No cervical motion tenderness; normal uterus; mild generalized pelvic tenderness. Examination of adnexa limited by habitus
Laboratory studies:
Urine pregnancy test: Negative Hb: 5.4 g/dL
How would you manage this patient?
The patient had a presumed heavy anovulatory bleed leading to significant anemia. The patient was admitted to the hospital and transfused 2 units of packed red blood cells and adminis- tered a 1-Lfluid bolus of normal saline. An endometrial biopsy was performed. After the transfusion, she felt much improved and her tachycardia resolved. Repeat hemoglobin drawn 4 hours after the transfusion was 7.8 g/dL. Because of the heaviness of the bleeding and significant anemia, the patient was started on high-dose intravenous estrogen for 24 hours.
The bleeding decreased substantially and the patient was then switched to 3 times a day dosing of a combined monophasic oral contraceptive containing 35μg of ethinyl estradiol for a 7-day period, followed by once daily dosing. Her bleeding resolved. Her endometrial biopsy showed proliferative endo- metrium with stromal breakdown. She was seen in follow-up, and continued on cyclic oral contraceptive pills for long-term management of her bleeding. Her acne and hirsutism in com- bination with her abnormal bleeding were strongly indicative of polycystic ovarian syndrome (PCOS), which was addressed separately at her follow-up visit.
Treatment of heavy bleeding
Effective treatment of heavy bleeding requires determining the cause. A urine pregnancy test should be performed in all reproductive-aged patients with unexplained bleeding as pregnancy-related bleeding is managed completely differently from other causes, and undiagnosed ectopic pregnancy is life threatening. The timing of the bleeding episodes must be determined, as it can help differentiate bleeding from the different causes. The PALM-COEIN system classifies uterine bleeding abnormalities by their pattern and etiology [1]. In this
Acute Care and Emergency Gynecology, ed. David Chelmow, Christine R. Isaacs and Ashley Carroll. Published by Cambridge University Press.
© Cambridge University Press 2015.
instance, a clinical picture of irregular, unpredictable bleeding episodes is present. Based on the history and clinicalfindings obtained during examination of the patient, a picture of abnor- mal uterine bleeding with ovulatory dysfunction (AUB-O) is most likely. The patient is obese and has clinical signs of androgen excess with hirsutism and acne, making PCOS the probable cause of her chronic anovulation. Her history sug- gests that the problem is longstanding, which is typical for PCOS. Given her uterus was felt to be normal on palpation, a structural problem such as a large myoma is less likely.
However, her anovulatory bleeding could be compounded by a small submucosal myoma or endometrial polyp.
Patients with anovulation can have significant bleeding leading to life-threatening volume loss and hemodynamic instability. Patients with heavy bleeding and hypovolemia should have intravenous access for fluid administration and if need be, transfusion. Assessment of blood loss and hemo- dynamic status of the patient will dictate the need for surgical or medical management. Hemoglobin and hematocrit status should be obtained. Blood products should be cross-matched for patients who have symptomatic hypovolemia or life- threatening acute bleeding. Patients with lesser bleeding but where transfusion may be necessary should have a type and screen sent. The patient should be hemodynamically stabilized while completing the evaluation and initiating therapy.
Thyroid-stimulating hormone (TSH) and prolactin levels can be drawn to rule out other possible etiologies of heavy AUB, such as significant thyroid abnormalities and hyperpro- lactinemia, which are common causes of lighter bleeding or amenorrhea, but less frequent causes of heavy bleeding. Ultra- sound is warranted to rule out an anatomic abnormality leading to excessive bleeding, particularly if the pelvic examin- ation suggests a uterine abnormality. Screening for possible underlying clotting disorder should be done by way of thor- ough patient history, especially in younger patients. Coagula- tion studies should be drawn if the patient has a history of heavy bleeding associated with procedures, recurrent epistaxis, easy bruising, frequent gum bleeding, or family history of bleeding symptoms. Coagulation disorders are more common than previously thought, with up to 20% of women with heavy menstrual bleeding potentially having an underlying coagula- tion disorder [2]. To assess for coagulation disorder, complete blood count with platelets, prothrombin time, and partial thromboplastin time should be drawn, with further testing depending on the results.
Patients with AUB-O continuously produce normal levels of estrogen. They have absent or infrequent ovulation, and consequently absent or infrequent endogenous progesterone to counteract estrogen-stimulated endometrial proliferation.
Without progesterone withdrawal to help stabilize and control this growth, a fragile, unstable, thickened vascular endometrial layer forms that is prone to intermittent sloughing. As in this patient, the bleeding can be very heavy and prolonged [3].
Progestin is the treatment of choice in women with light and
moderate bleeding. Progestin requires an adequately thick proliferative endometrium on which to work. With heavy bleeding, the endometrial lining becomes denuded. Estrogen becomes the treatment of choice to help stimulate the growth of the endometrium. Once bleeding has decreased, the estrogen-stimulated endometrial growth is sufficient to respond to progestin [4]. The need to restore an adequate endometrial lining in women with heavy anovulatory bleeding explains their potential poor response to progestin alone, and the preference for high-dose estrogen. High-dose estrogen also serves to stimulate clotting of vessels within the endometrial lining, which in turn decreases the vaginal bleeding [5]. The recurrent heavy bleeding episodes are caused by the instability of the endometrial layer and its irregularity [4].
Prolonged unopposed estrogen is the predominant risk factor for endometrial hyperplasia and cancer. The risk of endometrial cancer in women aged 20–34 with anovulatory bleeding is 1.6% and for women aged 35–44 it is 6.2% [3].
Given the chronicity of her anovulation and unopposed estro- gen exposure, her risk of developing endometrial hyperplasia or cancer is increased and her endometrium should be evalu- ated. Per the American College of Obstetricians and Gynecolo- gists, any patient younger than 45 years of age with AUB and unopposed estrogen exposure, failed medical management, or persistent vaginal bleeding, requires endometrial sampling [1].
This patient had evidence of prolonged unopposed estrogen and appropriately underwent endometrial sampling. Her biopsy showed proliferative endometrium with stromal break- down, a typicalfinding in anovulatory bleeding, and effectively confirmed the absence of hyperplasia or cancer.
Given her acute blood loss and hypovolemia, conjugated estrogen was administered. She was administered 25 mg IV conjugated estrogen every 4 hours for a total of 24 hours. As an alternative, high-dose oral contraceptives (Table 69.1[2]) can be administered. High doses of estrogen can cause nausea and vomiting, so anti-emetics can be administered prophylacti- cally. Most patients will have resolution or marked decrease in vaginal bleeding, allowing for transition to combined oral contraceptive pills. This regimen should be for seven days, three times daily, and then decreased to daily dosing [2]. Some providers use more complicated tapers, but these are often difficult for patients to follow. When initiating estrogen-based contraception, patients are carefully screened for potential contraindications. These contraindications do not necessarily apply in situations of acute, potentially life-threatening vaginal bleeding. In this situation the risks of the bleeding are much higher, and the estrogen can be used very short term, limiting the risks of the medication. Minor contraindications to estrogen-based contraception like smoking and older age or hypertension should not preclude short-course high-dose estrogen. Surgery should be reserved for treatment failure or situations where bleeding is profuse and there is insufficient time for medical management. Dilation and curettage is usu- ally attemptedfirst, although curettage of an already denuded
endometrium may not be effective. Endometrial ablation, uter- ine artery embolization, or hysterectomy may be required if curettage fails. Curettage will treat only the acute bleeding and not prevent future episodes [2].
The patient requires long-term progestin administration to prevent recurrent episodes. Oral contraceptives are an easy formulation, and give other benefits in terms of contracep- tion and improvement in PCOS-related hair growth and acne. This patient had no contraindications, and should plan on staying on her oral contraceptives long term. Unless she corrects her underlying PCOS through weight loss or other means, she should expect her abnormal bleeding will recur if she stops.
Other therapies can be used for patients who present with minimal-to-moderate acute vaginal bleeding (Table 69.1).
Use of progestin alone or combined oral contraceptives are effective. One study found that bleeding stopped in 88% of participants who took combined oral contraceptives and in 76% of women who took medroxyprogesterone acetate [6].
Alternate progestin or combined oral contraceptive formula- tions are also likely effective. Another option is the use of tranexamic acid; however, its use has only been studied in patients with chronic AUB [2].
Key teaching points
Establishing the etiology of abnormal uterine bleeding (AUB) will help in determining appropriate management.
The PALM-COEIN system was intended to help clarify the diagnosis of AUB.
Patients with heavy bleeding need assessment of hemodynamic parameters, and may need blood replacement.
Pharmacological management isfirst-line therapy for treatment of acute abnormal uterine bleeding with ovulatory dysfunction (AUB-O). Alternatives include intravenous conjugated estrogen, combined oral contraceptive pills, oral progestin, or tranexamic acid.
Progestin alone is typically adequate for moderate-to-light bleeding. For patients with heavy bleeding, estrogen is typically required.
Surgical treatment should be reserved for patients failing medical management.
Patients with life-threatening AUB-O are at risk for recurrence, as well as hyperplasia or cancer, unless the underlying problem is corrected or progestin is administered long term.
References
1. American College of Obstetricians and Gynecologists. Diagnosis of abnormal uterine bleeding in reproductive-aged women. Practice Bulletin No. 128.
Obstet Gynecol2012;120:197–206.
2. American College of Obstetricians and Gynecologists. Management of acute abnormal bleeding in nonpregnant reproductive-aged women. Committee Opinion No. 557.Obstet Gynecol 2013;121:891–6.
3. American College of Obstetricians and Gynecologists. Management of abnormal uterine bleeding associated with ovulatory dysfunction. Practice Bulletin No. 136.Obstet Gynecol 2013;122:179–85.
4. Bayer SR, DeCherney AH, Clinical manifestations and treatment of dysfunctional uterine bleeding,JAMA 1993;269:1823–8.
5. Heistinger M, Stockenhuber F, Schneider B, et al. Effect of conjugated
estrogens on platelet function and prostacyclin generation in CRF.Kidney Int1990;38:1181–6.
6. Munro MG, Mainor N, Basu R, Brisinger M, Barreda L. Oral medroxyprogesterone acetate and combination oral contraceptives for acute uterine bleeding: a randomized controlled trial.Obstet Gynecol 2006;108:924–9.
Table 69.1 Treatment options for acute abnormal uterine bleeding from AUB-O
Drug Dose Frequency
Conjugated equine estrogen 25 mg IV Every 4–6 hours for total of 24 h
Combined oral contraceptives Monophasic pill with minimum of 35μg ethinyl estradiol PO 3 times a day for 7 days
Medroxyprogesterone acetate 20 mg PO 3 times a day for 7 days
Tranexamic acid 1.3 g PO or 10 mg/kg IV 3 times a day for 5 days
Adapted from American College of Obstetricians and Gynecologists [2].
AUB-O, abnormal uterine bleeding with ovulatory dysfunction; IV, intravenous; PO,per os(orally).
Case 69: A 28-year-old woman with irregular bleeding requiring transfusion