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The American College of

Obstetricians and Gynecologists


WOMENS HEALTH CARE PHYSICIANS

COMMITTEE OPINION
.UMBERs!PRIL

Committee on Gynecologic Practice


This document reflects emerging clinical and scientific advances as of the date issued and is subject to change. The information should
not be construed as dictating an exclusive course of treatment or procedure to be followed.

Management of Acute Abnormal Uterine Bleeding in


Nonpregnant Reproductive-Aged Women
ABSTRACT: Initial evaluation of the patient with acute abnormal uterine bleeding should include a prompt
assessment for signs of hypovolemia and potential hemodynamic instability. After initial assessment and stabi-
lization, the etiologies of acute abnormal uterine bleeding should be classified using the PALMCOEIN system.
Medical management should be the initial treatment for most patients, if clinically appropriate. Options include
intravenous conjugated equine estrogen, multi-dose regimens of combined oral contraceptives or oral progestins,
and tranexamic acid. Decisions should be based on the patients medical history and contraindications to therapies.
Surgical management should be considered for patients who are not clinically stable, are not suitable for medical
management, or have failed to respond appropriately to medical management. The choice of surgical manage-
ment should be based on the patients underlying medical conditions, underlying pathology, and desire for future
fertility. Once the acute bleeding episode has been controlled, transitioning the patient to long-term maintenance
therapy is recommended.

Abnormal uterine bleeding (AUB) may be acute or venous lines should be initiated rapidly as should the
chronic and is defined as bleeding from the uterine cor- preparation for blood transfusion and clotting factor
pus that is abnormal in regularity, volume, frequency, or replacements. After the initial assessment and stabili-
duration and occurs in the absence of pregnancy (1, 2). zation, the next step is to evaluate for the most likely
Acute AUB refers to an episode of heavy bleeding that, etiology of acute AUB so that the most appropriate and
in the opinion of the clinician, is of sufficient quantity to effective treatment strategy to control the bleeding can
require immediate intervention to prevent further blood be chosen.
loss (1). Acute AUB may occur spontaneously or within
the context of chronic AUB (abnormal uterine bleeding Etiologies of Acute Abnormal Uterine
present for most of the previous 6 months). The general Bleeding
process for evaluating patients who present with acute The etiologies of acute AUB, which can be multifacto-
AUB can be approached in three stages: 1) assessing rap- rial, are the same as the etiologies of chronic AUB. The
idly the clinical picture to determine patient acuity, 2) Menstrual Disorders Working Group of the International
determining most likely etiology of the bleeding, and 3) Federation of Gynecology and Obstetrics proposed a
choosing the most appropriate treatment for the patient. classification system and standardized terminology for
the etiologies of the symptoms of AUB, which has been
Assessment of the Patient With Acute approved by the International Federation of Gynecology
Abnormal Uterine Bleeding and Obstetrics executive board and supported by the
Initial evaluation of the patient with acute AUB should American College of Obstetricians and Gynecologists (1,
include a prompt assessment for signs of hypovolemia 2). With this system, the etiologies of AUB are class-
and potential hemodynamic instability. If the patient is ified as related to uterine structural abnormalities and
hemodynamically unstable or has signs of hypovolemia, unrelated to uterine structural abnormalities and cat-
intravenous access with a single or two large bore intra- egorized following the acronym PALMCOEIN: Polyp,

VOL. 121, NO. 4, APRIL 2013 OBSTETRICS & GYNECOLOGY 891


Adenomyosis, Leiomyoma, Malignancy and hyperplasia,
Coagulopathy, Ovulatory dysfunction, Endometrial, Iatro- Box 1. Clinical Screening for an
genic, and Not otherwise classified (Fig. 1). Determining Underlying Disorder of Hemostasis
the most likely etiology of acute AUB is essential for in the Patient With Excessive
choosing the most appropriate and effective management Menstrual Bleeding A
for the individual patient and is accomplished by obtain-
ing a history, performing a physical examination, and Initial screening for an underlying disorder of hemostasis
requesting laboratory and imaging tests, when indicated. in patients with excessive menstrual bleeding should be
structured by the medical history. A positive screening
History result* comprises the following circumstances:
Obtaining a thorough medical history should be guided s (EAVYMENSTRUALBLEEDINGSINCEMENARCHE
by the PALMCOEIN system and focused on details of s /NEOFTHEFOLLOWINGCONDITIONS
the current bleeding episode; related symptoms; and past
menstrual, gynecologic, and medical history; which can, Postpartum hemorrhage
in turn, guide appropriate laboratory and radiologic test- Surgery-related bleeding
ing. Up to 13% of women with heavy menstrual bleeding Bleeding associated with dental work
have some variant of von Willebrand disease and up s 4WOORMOREOFTHEFOLLOWINGCONDITIONS
to 20% of women may have an underlying coagulation Bruising, one to two times per month
disorder (24). Other coagulation factor deficiencies,
Epistaxis, one to two times per month
hemophilia, and platelet function disorders may be
associated with AUB in any age group. Using a screen- Frequent gum bleeding
ing tool in Box 1 can assist the clinician in determining Family history of bleeding symptoms
which patients may benefit from laboratory testing for
*Patients with a positive screening result should be considered
disorders of hemostasis. Additionally, systemic diseases, for further evaluation, including consultation with a hematolo-
such as leukemia and liver failure, and medications, such gist and testing for von Willebrand factor and ristocetin cofac-
as anticoagulants or chemotherapeutic agents, can impair tor.
coagulation and be associated with AUB. Modified from Kouides PA, Conard J, Peyvandi F, Lukes A, Kadir R.
(EMOSTASISANDMENSTRUATIONAPPROPRIATEINVESTIGATIONFORUNDER-
Physical Examination lying disorders of hemostasis in women with excessive menstrual
A physical examination of a patient who presents with bleeding. Fertil Steril 2005;84:134551.;0UB-ED=;&ULL4EXT=
acute AUB should focus on signs of acute blood loss

Abnormal uterine bleeding:


Ui>i>Lii`}1 
Uii>Lii`}1 

PALMstructural causes: COEINnonstructural causes:


Polyp (AUB-P) Coagulopathy (AUB-C)
Adenomyosis (AUB-A) Ovulatory dysfunction (AUB-O)
Leiomyoma (AUB-L) Endometrial (AUB-E)
Submucosal leiomyoma (AUB-LSM) Iatrogenic (AUB-I)
Other leiomyoma (AUB-LO) Not yet classified (AUB-N)
Malignancy and hyperplasia (AUB-M)

Fig. 1. Basic PALMCOEIN classification system for the causes of abnormal uterine bleeding in nonpregnant reproduc-
tive-aged women. This system, approved by the International Federation of Gynecology and Obstetrics, uses the term
abnormal uterine bleeding paired with terms that describe associated bleeding patterns (heavy menstrual bleeding
or intermenstrual bleeding), a qualifying letter (or letters) to indicate its etiology (or etiologies), or both. Abbreviation:
AUB indicates abnormal uterine bleeding. (Data from Munro MG, Critchley HO, Broder MS, Fraser IS. FIGO classifica-
tion 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;113:313. [PubMed] [Full Text]) A

892 Committee Opinion Management of Acute Abnormal Uterine Bleeding OBSTETRICS & GYNECOLOGY
(hypovolemia and anemia) and findings that suggest the and women with either abnormalities in initial labora-
etiology of the bleeding. The patient should be evalu- tory testing or positive screening results for disorders
ated to determine that she has acute AUB and not bleed- of hemostasis should be considered for specific tests
ing from other areas of the genital tract. Thus, a pelvic for von Willebrand disease and other coagulopathies,
examination (including a speculum examination and a including von Willebrandristocetin cofactor activity,
bimanual examination) should be performed to identify von Willebrand factor antigen, and factor VIII (2, 5).
any trauma to the genital tract and vaginal or cervical Based on the clinical presentation, a workup for thyroid
findings that could cause vaginal bleeding. The pelvic disorders, liver disorder, sepsis, or leukemia may be indi-
examination also will determine the amount and inten- cated. Endometrial tissue sampling should be performed
sity of bleeding and will identify any uterine enlargement in patients with AUB who are older than 45 years as a
or irregularity, which can be associated with a structural first-line test. Endometrial sampling also should be per-
cause of the acute AUB (leiomyoma). formed in patients younger than 45 years with a history
of unopposed estrogen exposure (such as seen in patients
Laboratory Testing and Imaging with obesity or polycystic ovary syndrome), failed medical
Laboratory evaluation of patients who present with management, and persistent AUB (2). In a stable patient,
acute AUB is recommended (Table 1). All adolescents a decision whether to perform a pelvic ultrasound exami-
nation should be based on the clinical judgment of the
examining clinician.
Table 1.,ABORATORY4ESTINGFORTHE%VALUATIONOF0ATIENTS Treatment
With Acute Abnormal Uterine Bleeding A
Limited evidence and expert opinion support recommen-
Laboratory Evaluation Specific Laboratory Tests dations for treatment. Choice of treatment for acute AUB
depends on clinical stability, overall acuity, suspected
)NITIALLABORATORYTESTING s#OMPLETEBLOODCOUNT etiology of the bleeding, desire for future fertility, and
s"LOODTYPEANDCROSSMATCH underlying medical problems. The two main objectives
s0REGNANCYTEST of managing acute AUB are: 1) to control the current epi-
sode of heavy bleeding and 2) to reduce menstrual blood
)NITIALLABORATORYEVALUATIONFOR s0ARTIALTHROMBOPLASTINTIME loss in subsequent cycles. Medical therapy is considered
DISORDERSOFHEMOSTASIS s0ROTHROMBINTIME the preferred initial treatment (Table 2). However, certain
s!CTIVATEDPARTIALTHROMBO situations may call for prompt surgical management (6).
PLASTINTIME Studies of treatments of acute AUB are limited, and only
s&IBRINOGEN one treatment (intravenous [IV] conjugated equine estro-
gen) is specifically approved by the U.S. Food and Drug
)NITIALTESTINGFOR sVON7ILLEBRANDFACTORANTIGEN
Administration for the treatment of acute AUB.
VON7ILLEBRANDDISEASE
s2ISTOCETINCOFACTORASSAY
s&ACTOR6))) Medical Management
/THERLABORATORYTESTSTO s4HYROID STIMULATINGHORMONE Hormonal management is considered the first line of
CONSIDER medical therapy for patients with acute AUB without
s3ERUMIRON TOTALIRONBINDING
known or suspected bleeding disorders. Treatment options
CAPACITY ANDFERRITIN
include IV conjugated equine estrogen, combined oral
s,IVERFUNCTIONTESTS contraceptives (OCs), and oral progestins. In one ran-
sChlamydia trachomatis domized controlled trial of 34 women, IV conjugated
equine estrogen was shown to stop bleeding in 72% of

!DULTWOMENWHORECEIVEPOSITIVERESULTSFORRISKOFBLEEDINGDISORDERSORWHO
HAVEABNORMALINITIALLABORATORYTESTRESULTSFORDISORDERSOFHEMOSTASISSHOULD participants within 8 hours of administration compared
UNDERGOTESTINGFORVON7ILLEBRANDDISEASE!DOLESCENTSWITHHEAVYMENSESSINCE with 38% of participants treated with a placebo (7).
MENARCHEWHOPRESENTWITHACUTEABNORMALUTERINEBLEEDINGALSOSHOULDUNDERGO Little data exist regarding the use of IV estrogen in
TESTINGFORVON7ILLEBRANDDISEASE patients with cardiovascular or thromboembolic risk

#ONSULTATIONWITHAHEMATOLOGISTCANAIDININTERPRETINGTHESETESTRESULTS)FANY factors.
OFTHESEMARKERSAREABNORMALLYLOW AHEMATOLOGISTSHOULDBECONSULTED Combined OCs and oral progestins, taken in multi-
$ATAFROM*AMES!( +OUIDES0! !BDUL +ADIR2 $IETRICH*% %DLUND- &EDERICI dose regimens, also are commonly used for acute AUB.
!" ETAL%VALUATIONANDMANAGEMENTOFACUTEMENORRHAGIAINWOMENWITHAND
WITHOUTUNDERLYINGBLEEDINGDISORDERSCONSENSUSFROMANINTERNATIONALEXPERT
One study compared participants who underwent therapy
PANEL%UR*/BSTET'YNECOL2EPROD"IOLn.ATIONAL(EART ,UNG with OCs administered three times daily for 1 week with
AND"LOOD)NSTITUTE4HEDIAGNOSIS EVALUATION ANDMANAGEMENTOFVON7ILLEBRAND those who underwent therapy with medroxyprogester-
DISEASE.)(0UBLICATION.O "ETHESDA-$ .(,")!VAILABLEAT one acetate administered three times daily for 1 week for
HTTPWWWNHLBINIHGOVGUIDELINESVWDVWDPDF2ETRIEVED$ECEMBER 
and$IAGNOSISOFABNORMALUTERINEBLEEDINGINREPRODUCTIVE AGEDWOMEN0RACTICE
the treatment of acute AUB (8). The study found that
"ULLETIN.O!MERICAN#OLLEGEOF/BSTETRICIANSAND'YNECOLOGISTS/BSTET bleeding stopped in 88% of women who took OCs and
'YNECOLn 76% of women who took medroxyprogesterone acetate

VOL. 121, NO. 4, APRIL 2013 Committee Opinion Management of Acute Abnormal Uterine Bleeding 893
Table 2.-EDICAL4REATMENT2EGIMENSA
Potential Contraindications
and Precautions According to
Drug Source Suggested Dose Dose Schedule FDA Labeling*

#ONJUGATEDEQUINE $E6ORE'2 /WENS/ +ASE. MG)6 %VERYnHOURS #ONTRAINDICATIONSINCLUDE BUTARE


ESTROGREN 5SEOFINTRAVENOUS0REMARIN FORHOURS NOTLIMITED TOBREASTCANCER ACTIVE
INTHETREATMENTOF ORPASTVENOUSTHROMBOSISOR
DYSFUNCTIONALUTERINE ARTERIALTHROMBOEMBOLICDISEASE
BLEEDINGADOUBLE BLIND ANDLIVERDYSFUNCTIONORDISEASE
RANDOMIZEDCONTROLSTUDY 4HEAGENTSHOULDBEUSEDWITH
/BSTET'YNECOL CAUTIONINPATIENTSWITHCARDIO
n VASCULARORTHROMBOEMBOLICRISK
FACTORS
#OMBINEDORAL -UNRO-' -AINOR. "ASU2 -ONOPHASICCOMBINED 4HREETIMESPERDAYFOR #ONTRAINDICATIONSINCLUDE BUTARE
CONTRACEPTIVES "RISINGER- "ARREDA,/RAL ORALCONTRACEPTIVETHAT DAYS NOTLIMITEDTO CIGARETTESMOKING
MEDROXYPROGESTERONEACETATE CONTAINSMICROGRAMS INWOMENAGEDYEARSOROLDER
ANDCOMBINATIONORAL OFETHINYLESTRADIOL HYPERTENSION HISTORYOFDEEPVEIN
CONTRACEPTIVESFORACUTEUTERINE THROMBOSISORPULMONARYEMBOLISM
BLEEDINGARANDOMIZED KNOWNTHROMBOEMBOLICDISORDERS
CONTROLLEDTRIAL/BSTET'YNECOL CEREBROVASCULARDISEASE ISCHEMIC
n HEARTDISEASE MIGRAINEWITHAURA
CURRENTORPASTBREASTCANCER
SEVERELIVERDISEASE DIABETESWITH
VASCULARINVOLVEMENT VALVULAR
HEARTDISEASEWITHCOMPLICATIONS
ANDMAJORSURGERYWITHPROLONGED
IMMOBILIZATION
-EDROXYPRO -UNRO-' -AINOR. "ASU2 MGORALLY 4HREETIMESPERDAYFOR #ONTRAINDICATIONSINCLUDE BUTARE
GESTERONEACETATE "RISINGER- "ARREDA,/RAL DAYS NOTLIMITEDTO ACTIVEORPASTDEEP
MEDROXYPROGESTERONEACETATE VEINTHROMBOSISORPULMONARY
ANDCOMBINATIONORALCONTRACEP EMBOLISM ACTIVEORRECENTARTERIAL
TIVESFORACUTEUTERINEBLEEDING THROMBOEMBOLICDISEASE CURRENTOR
ARANDOMIZEDCONTROLLEDTRIAL PASTBREASTCANCER ANDIMPAIRED
/BSTET'YNECOLn LIVERFUNCTIONORLIVERDISEASE
4RANEXAMICACID *AMES!( +OUIDES0! GORALLY 4HREETIMESPERDAY #ONTRAINDICATIONSINCLUDE BUTARE
!BDUL +ADIR2 $IETRICH*% OR FORDAYS NOTLIMITEDTO ACQUIREDIMPAIRED
%DLUND- &EDERICI!" ETAL MGKG)6MAXIMUM EVERYHOURS COLORVISIONANDCURRENTTHROMBOTIC
%VALUATIONANDMANAGEMENTOF MGDOSE ORTHROMBOEMBOLICDISEASE4HE
ACUTEMENORRHAGIAINWOMEN AGENTSHOULDBEUSEDWITHCAUTION
WITHANDWITHOUTUNDERLYING INPATIENTSWITHAHISTORYOF
BLEEDINGDISORDERSCONSENSUS THROMBOSISBECAUSEOFUNCERTAIN
FROMANINTERNATIONALEXPERT THROMBOTICRISKS ANDCONCOMITANT
PANEL%UR*/BSTET'YNECOL ADMINISTRATIONOFCOMBINEDORAL
2EPROD"IOLn CONTRACEPTIVESNEEDSTOBECARE
FULLYCONSIDERED

!BBREVIATIONS&$!INDICATES53&OODAND$RUG!DMINISTRATION)6 INTRAVENOUSLY

4HE53&OODAND$RUG!DMINISTRATIONSLABELINGCONTAINSEXHAUSTIVELISTSOFCONTRAINDICATIONSFOREACHOFTHESETHERAPIES)NTREATINGWOMENWITHACUTEABNORMALUTERINE
BLEEDING PHYSICIANSOFTENMUSTWEIGHTHERELATIVERISKSOFTREATMENTAGAINSTTHERISKOFCONTINUEDBLEEDINGINTHECONTEXTOFTHEPATIENTSMEDICALHISTORYANDRISKFACTORS
4HESEDECISIONSMUSTBEMADEONACASE BY CASEBASISBYTHETREATINGCLINICIAN

/THERCOMBINEDORALCONTRACEPTIVEFORMULATIONS DOSAGES ANDSCHEDULESALSOMAYBEEFFECTIVE

/THERPROGESTINSSUCHASNORETHINDRONEACETATE DOSAGES ANDSCHEDULESALSOMAYBEEFFECTIVE

/THERDOSAGESANDSCHEDULESALSOMAYBEEFFECTIVE

894 Committee Opinion Management of Acute Abnormal Uterine Bleeding OBSTETRICS & GYNECOLOGY
within a median time of 3 days. For all patients, the Surgical Management
contraindications to these therapies need to be consid- The need for surgical treatment is based on the clinical
ered before administration. Consultation with the Cen- stability of the patient, the severity of bleeding, contra-
ters for Disease Control and Preventions Medical indications to medical management, the patients lack
Eligibility Criteria for Contraceptive Use (9, 10) and U.S. of response to medical management, and the underlying
Food and Drug Administration labeling information (11) medical condition of the patient. Surgical options include
can be helpful in determining which patients may or may dilation and curettage (D&C), endometrial ablation, uter-
not be treated with OCs or progestin alone. Other OC ine artery embolization, and hysterectomy. The choice of
and progestin formulations and dose schedules may be surgical modality (eg, D&C versus hysterectomy) is based
equally effective. on the aforementioned factors plus the patients desire
Antifibrinolytic drugs, such as tranexamic acid, work for future fertility. Specific treatments, such as hysteros-
by preventing fibrin degradation and are effective treat- copy with D&C, polypectomy, or myomectomy, may be
ments for patients with chronic AUB. They have been required if structural abnormalities are suspected as the
shown to reduce bleeding in these patients by 3055% cause of acute AUB. Dilation and curettage alone (with-
(12, 13). Tranexamic acid effectively reduces intraoper- out hysteroscopy) is an inadequate tool for evaluation
ative bleeding and the need for transfusion in surgical of uterine disorders and may provide only a temporary
patients and is likely effective for patients with acute reduction in bleeding (cycles after the D&C will not be
AUB, although it has not been studied for this indica- improved) (18). Dilation and curettage with concomitant
tion (14, 15). Experts recommend using either oral or hysteroscopy may be of value for those patients in whom
IV tranexamic acid for the treatment of acute AUB (15). intrauterine pathology is suspected or a tissue sample is
Intrauterine tamponade with a 26F Foley catheter infused desired (18). Case reports of uterine artery embolization
with 30 mL of saline solution has been reported to control and endometrial ablation show that these procedures suc-
bleeding successfully and also may be considered (15, 16). cessfully control acute AUB (19, 20). Endometrial abla-
Once the acute episode of bleeding has been con- tion, although readily available in most centers, should be
trolled, multiple treatment options are available for considered only if other treatments have been ineffective
long-term treatment of chronic AUB. Effective medical
or are contraindicated, and it should be performed only
therapies include the levonorgestrel intrauterine system,
when a woman does not have plans for future childbear-
OCs (monthly or extended cycles), progestin therapy (oral
ing and when the possibility of endometrial or uterine
or intramuscular), tranexamic acid, and nonsteroidal anti-
cancer has been reliably ruled out as the cause of the acute
inflammatory drugs (6). If a patient is receiving IV con-
AUB. Hysterectomy, the definitive treatment for control-
jugated equine estrogen, the health care provider should
ling heavy bleeding, may be necessary for patients who do
add progestin or transition to OCs. Unopposed estrogen
not respond to medical therapy.
should not be used as long-term treatment for chronic
AUB. Conclusions and Recommendations
Patients with known or suspected bleeding disorders
may respond to the hormonal and nonhormonal manage- Based on the available evidence and expert opinion, the
ment options listed earlier in this section. Consultation American College of Obstetricians and Gynecologists
with a hematologist is recommended for these patients, Committee on Gynecologic Practice makes the following
especially if bleeding is difficult to control or the gyne- conclusions and recommendations:
cologist is unfamiliar with the other options for medical s 4HEETIOLOGIESOFACUTE!5"SHOULDBECLASSIFIEDBASED
management. Desmopressin may help treat acute AUB on the PALMCOEIN system: Polyp, Adenomyosis,
in patients with von Willebrand disease if the patient is Leiomyoma, Malignancy and hyperplasia, Coagulo-
known to respond to that agent. It may be administered pathy, Ovulatory dysfunction, Endometrial, Iatro-
by intranasal inhalation, intravenously, or subcutaneous- genic, and Not otherwise classified.
ly (17). This agent must be used with caution because of
the risks of fluid retention and hyponatremia and should s -EDICALMANAGEMENTSHOULDBETHEINITIALTREATMENT
not be administered to patients with massive hemor- for most patients, if clinically appropriate. Options
rhage who are receiving IV fluid resuscitation because of include IV conjugated equine estrogen, multi-dose
issues with fluid overload (15). Recombinant factor VIII regimens of OCs or oral progestins, and tranexamic
and von Willebrand factor also are available and may be acid. Decisions should be based on the patients
required to control severe hemorrhage (5). Other factor medical history and contraindications to therapies.
deficiencies may need factor-specific replacement. s 4HE NEED FOR SURGICAL TREATMENT IS BASED ON THE
Patients with bleeding disorders or platelet function clinical stability of the patient, the severity of bleed-
abnormalities should avoid nonsteroidal antiinflamma- ing, contraindications to medical management, the
tory drugs because of their effect on platelet aggregation patients lack of response to medical management,
and their interaction with drugs that might affect liver and the underlying medical condition of the patient.
function and the production of clotting factors (17). The choice of surgical modality should be based on

VOL. 121, NO. 4, APRIL 2013 Committee Opinion Management of Acute Abnormal Uterine Bleeding 895
the aforementioned factors plus the patients desire 11. Food and Drug Administration. FDA online label reposi-
for future fertility. tory. Available at: http://labels.fda.gov. Retrieved December
5, 2012. A
s /NCETHEACUTEBLEEDINGEPISODEHASBEENCONTROLLED
transitioning the patient to long-term maintenance 12. Lethaby A, Farquhar C, Cooke I. Antifibrinolytics for heavy
therapy is recommended. menstrual bleeding. Cochrane Database of Systematic
Reviews 2000, Issue 4. Art. No.: CD000249. DOI: 10.1002/
14651858.CD000249. [PubMed] [Full Text] A
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896 Committee Opinion Management of Acute Abnormal Uterine Bleeding OBSTETRICS & GYNECOLOGY