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Contents lists available at ScienceDirect

European Journal of Obstetrics & Gynecology and

Reproductive Biology
journal homepage: www.elsevier.com/locate/ejogrb

Review

Evaluation and management of acute menorrhagia in women with and without

underlying bleeding disorders: consensus from an international expert panel
Andra H. James a,*, Peter A. Kouides b, Rezan Abdul-Kadir c, Jennifer E. Dietrich d, Mans Edlund e,
Augusto B. Federici f, Susan Halimeh g, Pieter Willem Kamphuisen h, Christine A. Lee i,
Oscar Martnez-Perez j, Claire McLintock k, Flora Peyvandi l, Claire Philipp m,
Jeffrey Wilkinson n, Rochelle Winikoff o
a

Womens Hemostasis and Thrombosis Clinic, Duke University Medical Center, Durham, NC, USA
Mary M. Gooley Hemophilia Treatment Center, Rochester General Hospital, Rochester, NY, USA
c
Department of Obstetrics and Gynaecology, Royal Free Hospital, London, UK
d
Division of Pediatric & Adolescent Gynecology, Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX, USA
e
Department of Obstetrics and & Gynecology, Danderyds University Hospital, Stockholm, Sweden
f
Division of Hematology and Transfusion Medicine, Luigi Sacco University Hospital, Department of Internal Medicine, University of Milan, Milan, Italy
g
Centre for Coagulation Disorders Rhine-Ruhr Area, Germany
h
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
i
Emeritus Professor, University of London, London, UK
j
Department Obstetrics and Gynecology, Fundacion Jimenez Diaz Hospital, Madrid, Spain
k
Department of OB/GYN, National Womens Health, Auckland City Hospital, Auckland, New Zealand
l
Department for Diagnosis and Treatment of Coagulopathies, Angelo Bianchi Bonomi Haemophilia Thrombosis Centre, IRCCS Maggiore Policlinico Hospital,
Mangiagalli and Regina Elena Foundation and Universita` di Milano, Milan, Italy
m
Division of Hematology, Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
n
Obstetrics and Gynecology, Minimally Invasive Gynecologic Surgery, Duke University Medical Center, Durham, NC, USA
o
Hemophilia Treatment Center, CHU Sainte-Justine, Montreal, Quebec, Canada
b

A R T I C L E I N F O

A B S T R A C T

Article history:
Received 5 October 2010
Received in revised form 25 February 2011
Accepted 30 April 2011

Acute menorrhagia is a common gynecological disorder. Prevalence is high among women with
inherited bleeding disorders and recent guidance for optimal management is lacking. Following a
comprehensive review of the literature, an international expert panel in obstetrics, gynecology and
hematology reached consensus on recommendations regarding the management of acute menorrhagia
in women without a diagnosed bleeding disorder, as well as in patients with von Willebrand disease,
platelet function disorders and other rare hemostatic disorders. The causes and predictors of acute
menorrhagia are discussed and special consideration is given for the treatment of women on
anticoagulation therapy. This review and accompanying recommendations will provide guidance for
healthcare practitioners in the emergency management of acute menorrhagia.
2011 Elsevier Ireland Ltd. All rights reserved.

Keywords:
Acute menorrhagia
Bleeding disorder
Hemostasis management
Consensus
Coagulation factor

Contents
1.
2.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.1.
Results of PubMed search. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Causes and predictors of acute menorrhagia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.2.
Prevalence of hemostasis disorders in acute menorrhagia . . . . . . . . . . . . . . . . . . . . . . . . .
2.3.
Evaluation of acute menorrhagia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.4.
Optimal management strategies for acute menorrhagia in patients without a diagnosed
2.5.
Hormonal treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.5.1.
Antibrinolytic treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.5.2.

...............
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bleeding disorder
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* Corresponding author. Tel.: +1 919 668 0011; fax: +1 919 681 7861.
E-mail address: james031@mc.duke.edu (A.H. James).
0301-2115/$ see front matter 2011 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.ejogrb.2011.04.025

Please cite this article in press as: James AH, et al. Evaluation and management of acute menorrhagia in women with and without
underlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/
j.ejogrb.2011.04.025

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3.
4.

2.5.3.
Surgical treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Multidisciplinary management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.5.4.
Management of acute menorrhagia in the patient with a hemostasis disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.6.
Management of acute menorrhagia in the patient with VWD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.6.1.
Management of acute menorrhagia in the patient with thrombocytopenia or a platelet function disorder.
2.6.2.
Specic treatment for various thrombocytopenic conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.6.3.
Management of acute menorrhagia in the patient with other rare bleeding disorders . . . . . . . . . . . . . . . . .
2.6.4.
Management of acute menorrhagia in the patient on anticoagulation therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.7.
Future perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction
Menorrhagia is a gynecological condition which adversely
affects quality of life for many women. Acute menorrhagia can be
dened as excessive menstrual or inter-menstrual bleeding
occurring in a woman of childbearing age requiring emergency
treatment excluding pregnancy, postpartum hemorrhage, trauma
and malignancy [1,2]. Menorrhagia is usually dened by blood
loss of over 80 mL per menstrual cycle, with anemia, low (below
normal) ferritin levels, passing clots greater than a 50 pence-coin
in size (1.1 in. or 2.8 cm in diameter) [3], and soaking of bed
clothes or through a pad or tampon within 1 h [3,4] also being
indicative of the condition. There are a variety of different causes
of menorrhagia, and gynecological evaluation is essential to tailor
management to the individual patient to prevent unnecessary
invasive procedures which may have limited effect. Inherited
bleeding disorders have been linked to a signicant prevalence of
menorrhagia [5], with von Willebrand disease (VWD), platelet
function disorder and factor XI deciency exhibiting a particularly
high frequency [5,6]. The incidence and clinical signicance of
acute menorrhagia in women with underlying disorders of
hemostasis, however, are often underestimated. Furthermore,
the lack of recent evidence for diagnostic and treatment strategies
in acute menorrhagia [7] necessitates the extrapolation from
evidence in chronic menorrhagia. Guidelines for the evaluation
and management of chronic menorrhagia in patients with an
underlying disorder of hemostasis such as VWD were recently
published following a consensus meeting of experts in hematology and obstetrics and gynecology [4]. To address the lack of
guidance for the management of acute menorrhagia, a further
meeting was held in November 2009 in London, UK, to reach
consensus on the evaluation and management of acute menorrhagia particularly in the setting of an underlying disorder of
hemostasis.
2. Methods
An extensive PubMed search was conducted to identify
pertinent literature and evidence to guide the consensus. The
terms acute menorrhagia, menorrhagia and transfusion and
severe menorrhagia were entered with no restrictions placed on
the dates of the search or the type of article, to ensure that all
potential articles were identied. These terms were crossreferenced with von Willebrand disease, coagulation factor
deciency and platelet function defect.
Acute menorrhagia has not previously been rigorously
dened. For the purpose of this consensus, the hematology
and obstetric and gynecology experts dened acute menorrhagia
as (1) life-threatening bleeding of uterine origin, (2) in the
absence of pregnancy or malignancy, (3) occurring in women
ranging from teen to perimenopausal age, (4) with or without
previously diagnosed bleeding disorders, (5) presenting to the

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emergency department (ED), (6) with a need for immediate

evaluation and treatment and (7) with potential need for both
hemostatic and gynecological management.
2.1. Results of PubMed search
The PubMed search yielded case reports, small case series,
review articles and guidelines, but no large observational
studies. Randomized trials were found that addressed menorrhagia, but only one small randomized trial was found that
addressed acute menorrhagia [8]. As a result, the recommendations provided in this consensus are based on the opinions of
experts.
2.2. Causes and predictors of acute menorrhagia
There are a number of causes of acute menorrhagia, ranging
from pathologies including systemic disease and coagulation
disorders to anatomic conditions and treatment with some
medications [9]. The causes of relevance to these guidelines, and
the age groups which they affect, are shown in Fig. 1. Other causes
that fall outside the present denition of acute menorrhagia
include pregnancy-related complications and gynecologic malignancy.
The most likely causes of acute menorrhagia are in part
determined by the age of the patient. Since the rst clinical
manifestation of menorrhagia is often related to the onset of
menarche, underlying causes are seldom identied before
adolescence [10]. Together with anovulatory bleeding, unidentied bleeding disorders are commonly associated with acute
menorrhagia in this age range [9]. As the age of women increases,
those suffering from acute menorrhagia with a history of
underlying bleeding disorders may experience acute bleeding
episodes due to continued sub-optimal management. Conversely,
acute menorrhagia occurring as a result of local pathology such as
broids or endometrial polyps is often not observed until women
reach their mid-thirties [9]; perimenopausal anovulatory bleeding is usually not observed until women reach their mid to late
forties [11].
2.3. Prevalence of hemostasis disorders in acute menorrhagia
VWD is one of the most common bleeding disorders associated
with menorrhagia, with an overall prevalence of 13% in women
presenting with chronic menorrhagia [6]. In turn, 7492% of
women with VWD experience menorrhagia, with the actual
prevalence dependent on the VWD type [1214]. Rare bleeding
disorders are also associated with menorrhagia. A review of the
literature on menorrhagia conducted in 2005 revealed a prevalence of 3570% for women with deciencies of factor I, XI or XIII
[15]. Factors II, V and X have also been associated with a high
prevalence of bleeding [16].

Please cite this article in press as: James AH, et al. Evaluation and management of acute menorrhagia in women with and without
underlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/
j.ejogrb.2011.04.025

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Fig. 1. Probable causes of acute menorrhagia by age group. The ends of the arrows in the gure show the age range that is relevant for each cause. Based on relevant available
literature [25,6971] and authors professional opinion/experience.

There are few prevalence studies of platelet disorders, including

thrombocytopenic as well as thrombocytopathic disorders, in the
setting of acute menorrhagia [17], and their prevalence may be
underestimated. Studies of menorrhagia have identied a number

of both inherited and acquired platelet disorders associated with

the condition [1822]. Based on the limited reports available,
immune thrombocytopenic purpura (ITP) may be one of the most
common causes of acute menorrhagia in adolescents [23]. As for

Table 1
Evaluation of acute menorrhagia.
Patient history

Vital signs

Speculum and pelvic examinations

Laboratory tests

Ultrasound

Menstrual
Medical
Bleeding
Medication, including use of hormonal contraceptives
Recent trauma
Blood pressure
Heart rate
Respiration rate
Oxygen saturation
Depending on the age of the patient and the clinicians judgment
Depending on the availability of the testing, the feasibility of obtaining
a meaningful specimen in the setting of ooding and the ability
to track the results
* Pap smear
* Endometrial biopsy
Immediate:
* Complete blood count
* Blood type and cross-match
* Pregnancy test
* Partial thromboplastin time (PTT)
* Activated partial thromboplastin time (aPTT)
* Fibrinogen level
* VWF levels (depending on availability for real-time analysis and appropriate
processing) [64,65] a
* Plasma sample for storage (refer to suitable guidelines on the handling and
storage of plasma sample) [66]
Additional:
* Serum iron, total iron binding capacity and ferritin
* Liver function
* Full hemostatic evaluation including the following tests if indicated
(i.e., past personal or family history to suggest an underlying disorder of hemostasis)
* Platelet aggregation and release studies (cannot be done at time of acute event)
* Factor IX, XI and XIII
* Fibrinolysis
* Thyroid stimulating hormone (TSH)
* Depending on clinical judgment (based on diagnostic suspicion
and the age of the patient, and availability of equipment)
* Intravaginal ultrasound (depending on whether the patient has been sexually active)

*
*
*
*
*
*
*
*
*
*
*

Please note that VWF levels may not be altered by modern oral contraceptives [67].

Please cite this article in press as: James AH, et al. Evaluation and management of acute menorrhagia in women with and without
underlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/
j.ejogrb.2011.04.025

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the prevalence of thrombocytopathic disorders in chronic menorrhagia, Philipp et al. reported that approximately half of patients
presenting with unexplained menorrhagia had a defect in platelet
aggregation and/or release [24,25].
2.4. Evaluation of acute menorrhagia
There was consensus that it is important to establish a diagnosis
for and underlying cause of the abnormal bleeding, as this will help
to ensure appropriate management of the bleeding and potentially
prevent further bleeding. The experts also reached a consensus on
how patients presenting with acute menorrhagia should be
managed. The recommended evaluation is summarized in Table
1. The evaluation comprises a combination of patient history,
including any family history (although lack of this should not
exclude a diagnosis of an inherited disorder), ultrasound imaging,
laboratory tests and speculum and pelvic examination. Depending
on the accessibility of testing, the feasibility of achieving a
meaningful specimen in the setting of acute menorrhagia and the
ability to track the results from the ED, the provider may want to
consider obtaining a Pap smear and endometrial biopsy at the time
of examination. Otherwise, these tests can be postponed until the
patient is stable and suitable follow-up provision is available.
Testing of hormone levels, while potentially useful in the
evaluation of continuing menorrhagia, is not essential in the
evaluation of acute menorrhagia and can also be postponed. Due to
the difculties in obtaining some of the coagulation tests, there
may be a tendency to withhold further evaluation; this can greatly
impact on patient care. A number of studies and other consensus
groups have highlighted the ongoing need to consider underlying
bleeding disorders, especially in adolescents presenting with acute
menorrhagia [4,5,9].

2.5. Optimal management strategies for acute menorrhagia in

patients without a diagnosed bleeding disorder
Algorithms for the management of acute menorrhagia have
been devised previously and these were considered during the
development of this consensus [26]. A range of rst-line treatment
options was devised (Table 2); the order of use and whether they
should be used alone or in combination is dependent on clinical
judgment and social and cultural aspects. The options for rst-line
therapy include hormonal, surgical, and hemostatic treatments.
2.5.1. Hormonal treatment
The suggested regimens for the administration of hormonal
preparations in acutely bleeding patients are detailed in Table 3.
Once the patient has been stabilized, these regimens should be
tapered to a maintenance dose. A variety of tapering regimens exist
[27]; suggested regimens are summarized in Table 4.
2.5.2. Antibrinolytic treatment
Tranexamic acid and aminocaproic acid are two commonly
used antibrinolytic agents. Although aminocaproic acid is still
used in certain countries to treat acute bleeding, it has been largely
replaced by tranexamic acid in countries where this is available.
Therefore, the following discussion will focus principally on
tranexamic acid. Tranexamic acid is used widely in the treatment
and prophylaxis of mucous membrane and post-surgical bleeding;
it is an effective rst-line treatment for menorrhagia [28]. As a
synthetic derivative of the amino acid lysine, tranexamic acid
exerts its antibrinolytic effect through the reversible blockade of
lysine-binding sites on plasminogen molecules. Both intravenous
(IV) and oral formulations are available, although the oral form is
not currently available in some countries. The IV formulation has a

Table 2
Treatment options for acute menorrhagia in patients without a diagnosed bleeding disorder [8,7077].
First line
 antibrinolytic agents
 hormonal agents (intravenous Premarin1 [Pzer Inc, New York, New York, USA] if available)
 balloon tamponade

this technique may provide a temporary measure to limit bleeding while further investigations are carried out or the patient is undergoing transfer to the
operating room or theatre

the use of this as a rst-line treatment would depend on the patient (e.g. age, ability to tolerate a pelvic examination), suspected pathology and the clinical
setting (such as availability of antibrinolytics and hormonal agents and whether the patient is hemodynamically unstable)
Second line (depending on the desire for future fertility)
 dilation and curettage (D & C), which would be rarely indicated in adolescents, but this technique has value if a tissue sample is needed for diagnosis.
This would be accompanied by a hysteroscopy if there is a high degree of suspicion of pathology (e.g. polyp)
 endometrial ablation, if no desire for future fertility
 uterine artery embolization, if no desire for future fertility or as a life-saving measure
 recombinant factor VIIa (rFVIIa), which would be considered if the patient is near death in an attempt to preserve the uterus and life
 hysterectomy
Maintenance therapy (once stabilized)
 hormonal agents

combined hormonal contraceptives

progestin only contraceptives including the levonorgestrel intrauterine device (Mirena1 [Bayer Corporation, Leverkusen, Germany], injections
(Depo-Provera1 [Pzer Inc, New York, New York, USA]) and the Implanon1 implant (Schering-Plough, Kenilworth, NJ, USA)

Table 3
Dose ranges of hormonal treatments in acute bleeding [27].
Hormone

Route

Protocol for acute menstrual cessation

Conjugated oestrogens
30 mg ethinyl estradiol/0.3 mg norgestrel
(or other 30 mg combination pill)
50 mg ethinyl estradiol/0.5 mg norgestrel
(or other 50 mg combination pill)
Norethindrone acetate
Medroxyprogesterone

IV
Oral

25 mg every 46 h until bleeding stops, consider re-evaluating need for continuation at 48 h

One tablet every 6 h until bleeding stops, consider re-evaluating at 48 h

Oral

One tablet every 6 h until bleeding stops, consider re-evaluating at 48 h

Oral
Oral

510 mg every 4 h
10 mg every 4 h (and up to 80 mg/day)

IV, intravenous.

Please cite this article in press as: James AH, et al. Evaluation and management of acute menorrhagia in women with and without
underlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/
j.ejogrb.2011.04.025

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Table 4
Protocols for tapering hormonal treatment to maintenance therapy [27].
Hormone

Tapering regimens

50 mg combination hormonal
contraceptive pill

May begin with this every 6 h orally until bleeding stops, then decrease to every 8 h
for 2 days and up to 7 days, then every 12 h for 2 days and up to 7 days, then daily
thereafter. If transitioning from IV Premarin, may step down to 50 mg pill every 6 h
or even every 8 h, then follow as above.
May begin with this every 6 h orally until bleeding stops, then decrease to every 8 h for 2 days and up to 7 days,
then every 12 h for 2 days and up to 7 days, then daily thereafter.
510 mg every 4 h orally until bleeding stops, then every 6 h for 4 days, then every 8 h for
3 days, then every 12 h for 2 days to 2 weeks, then daily thereafter. May switch over to this
after initial bleeding stops if megestrol acetate utilised for acute menstrual control.
10 mg every 4 h orally (max 80 mg) until bleeding stops, then every 6 h for 4 days, then
every 8 h for 3 days, then every 12 h for 2 days to 2 weeks, then daily thereafter.
May switch over to this after initial bleeding stops if megestrol acetate utilised for acute menstrual control.

3035 mg combination
hormonal contraceptive pill
Norethindrone acetate

Medroxyprogesterone

IV, intravenous.

faster onset of action and so may be more appropriate in some

cases of acute menorrhagia. Tranexamic acid is contraindicated in
patients with disseminated intravascular coagulation, venous or
arterial thromboembolism, macroscopic hematuria or color
blindness. Side-effects are uncommon but typically manifest as
nausea and dizziness which respond to reductions in dose. While
prolonged treatment may increase thrombotic tendency, largescale studies have revealed that the incidence of thrombosis in
women treated with tranexamic acid is similar to the spontaneous
incidence of thrombosis in untreated women [2931].
The usual IV dose of tranexamic acid is 10 mg/kg every 8 h and
the usual oral dose is 2025 mg/kg every 8 h. Various other dosing
regimens are available for the oral formulation and these are listed
in Table 5. No single dosing regimen has been demonstrated to be
superior, although higher doses (3 g daily) may be more effective in
acute menorrhagia than lower doses (2 g daily) [32]. In the United
States, a new oral sustained formulation has recently been
approved (dosed at two tablets of 650 mg each 1.3 g) orally three
times per day [33]. (Neither this formulation nor this dose was
studied in the treatment of acute menorrhagia.) Treatment
duration is usually tailored according to clinical bleeding and
may be stopped without tapering when heavy menstrual bleeding
subsides.
2.5.3. Surgical treatment
When medical therapy fails in the treatment of acute
menorrhagia, or if the patient has contraindications to medical
management (i.e., thromboembolic disease), surgical management
options must be considered. The choice of the surgical procedure is
dictated by the suspected etiology and the desire for maintaining
fertility after the procedure. Those procedures that can spare
fertility include: dilatation and curettage (D & C), hysteroscopy
with D & C, hysteroscopy with polypectomy or myomectomy and
endometrial balloon tamponade.
Endometrial balloon tamponade can be an effective means of
controlling acute menorrhagia and allowing stabilization of the
patient in anticipation of further medical (hemostatic, hormonal)
therapy or other surgical procedures. In a uterus less than 12

Table 5
Doses of tranexamic acid recommended for the treatment of acute menorrhagia.
Tranexamic acid (500 mg tablets)
500 mg four times daily
1.01.5 g three times daily
1 g every 6 h
3 g over the day or one pill six times daily
4 g daily for 35 days
Tranexamic acid (650 mg tablets) (e.g., LystedaTM) [68]
1.3 g three times daily for 5 days

weeks size, a Foley catheter with a 30 cc balloon can be inserted

through the cervix and inated with saline until resistance of the
myometrium is felt. Ultrasound can be helpful to diagnose
intrauterine pathology, to conrm adequate placement and
distension and to exclude ongoing bleeding above the balloon [34].
Uterine artery embolization (UAE) has been successful in the
control of acute menorrhagia [35]. The aorta is accessed via the
femoral artery, a pelvic angiogram is obtained, bleeding vessels are
identied and then occluded [36]. The procedure entails inherent
delay in transferring the patient to the angiography suite,
preparing the patient and performing the procedure, and it must
be regarded as second line therapy [36]. While successful
pregnancies have been reported after this procedure [37], rates
of pregnancy complications are increased after UAE and future
fertility is still generally considered a contraindication to this
procedure. Loss of ovarian function (transient or permanent) due
to embolization of utero-ovarian collaterals can occur after UAE,
leading to premature menopause. The risk of this complication is
age-related and reported to be 12% in women younger than 45
years [28]; thus, this option should only be used as a life-saving
measure in young women. Endometrial ablation has been
demonstrated to be an effective means of controlling acute men
orrhagia and has been proposed as an alternative to hysterectomy
in women who are poor surgical candidates [38]. However, it still
requires a minimum of local anesthesia or intravenous sedation,
must be performed in the operating room or theater, should not be
performed when malignancy has not been excluded and may not
be successful in the presence of severe bleeding [39,40]. Pregnancy
is contraindicated in women who have had endometrial ablation.
Hysterectomy is the most denitive surgical treatment of
menorrhagia, but can often be avoided by employing one or more
of the above measures. In a patient with acute, life-threatening
hemorrhage, hysterectomy should not be delayed in favor of
potentially less effective measures, especially if fertility is no
longer desired or possible.
2.5.4. Multidisciplinary management
Multidisciplinary management of acute menorrhagia between
gynecology, hematology, pharmacy and nursing staff can greatly
benet patient care. A sample care plan that ensures appropriate
orchestration of these elements is presented in Fig. 2. This plan is in
use at Sainte-Justine Hospital, Montreal, Canada, and has had a
positive impact both on the success of controlling heavy bleeding
and on improving the quality of care provided to women with
acute menorrhagia [41]. It has also been associated with other
benets such as increased investigation for bleeding disorders,
more consistent use of antibrinolytic agents, fewer surgical
interventions and fewer blood transfusions in adolescents
presenting with acute menorrhagia. Such a care plan can be

Please cite this article in press as: James AH, et al. Evaluation and management of acute menorrhagia in women with and without
underlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/
j.ejogrb.2011.04.025

G Model

EURO-7311; No. of Pages 11

6

A.H. James et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology xxx (2011) xxxxxx

Fig. 2. Sample care plan from the CHU Sainte-Justine, Montreal, Canada [42].

modied to suit institutional requirements and should conform to

usual care in that particular institution [42].
2.6. Management of acute menorrhagia in the patient with a
hemostasis disorder
The general approach to the management of acute menorrhagia in the patient with a disorder of hemostasis is generally as
described above with specics as described below. Measures to
control uterine bleeding should be implemented while correcting
deciencies of clotting factors or abnormalities of platelet
number or function. The relative importance of hemostatic,

hormonal and surgical treatment options will vary in each

clinical situation. When bleeding is uncontrolled and other
treatment options (hormonal therapy or antibrinolytics) either
have not yet been initiated or have not successfully elicited a
reduction in bleeding, we recommend endometrial balloon
tamponade with concomitant or subsequent hormonal and/or
hemostatic therapy.
2.6.1. Management of acute menorrhagia in the patient with VWD
There are specic considerations for the rst-line treatment of
acute menorrhagia in patients with VWD which combine
treatment options. Desmopressin must be used with caution, if

Please cite this article in press as: James AH, et al. Evaluation and management of acute menorrhagia in women with and without
underlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/
j.ejogrb.2011.04.025

G Model

EURO-7311; No. of Pages 11

A.H. James et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology xxx (2011) xxxxxx

at all, in cases of massive hemorrhage. Desmopressin causes uid

retention and patients receiving desmopressin should be uid
restricted, yet patients with acute menorrhagia commonly receive
at least 12 L of uid at the time of initial resuscitation. In the
absence of massive hemorrhage, the recommendation for rst-line
treatment of acute menorrhagia in patients with VWD is
desmopressin, which is frequently used in combination with an
antibrinolytic agent such as tranexamic acid (both for 23 days,
then tranexamic acid alone for 34 days). This is based on a report
that desmopressin and tranexamic acid together are more effective
than either agent alone [43] with the presumption that acute
menorrhagia is a clinical situation requiring as effective and rapid a
response to hemostatic therapy as possible. Ideally, this approach
should only be used in patients who have demonstrated a prior
response to desmopressin (dened as a doubling of the VWF levels
[14] and minimum VWF response of 50%) and in whom uid
overload would not be an issue. Factor concentrates (e.g.,
Haemate1 P/Humate1-P, CSL Behring, Marburg, Germany; Optivate1, Bio Products Laboratory, Elstree, UK; Alphanate1, Grifols UK
Ltd., Cambridge, UK; and Wilate1, Octapharma, Lachen,
Switzerland) are available [44] for VWF and FVIII replacement
and these should be used if desmopressin is contraindicated; for
example, in patients with no prior response (although if on-site
real-time VWF analysis is available, one could conceivably
measure post-desmopressin VWF levels 15 min post-infusion),
in patients with potential for uid overload, in patients with
ongoing bleeding, in patients who are undergoing surgery [45] or
in patients who are hemodynamically unstable. Maintenance
therapy in patients with VWD should be the same as recommended above for patients without a diagnosed bleeding disorder.
Intranasal or oral desmopressin, where available, could be added to
augment this therapy [46].
2.6.2. Management of acute menorrhagia in the patient with
thrombocytopenia or a platelet function disorder
Treatment for acute menorrhagia in patients with underlying
thrombocytopenia or a platelet function disorder should include
management of the underlying disorder. Platelet transfusion
should be considered rst-line therapy in patients with acute
menorrhagia and a platelet count <20,000/mL or <50,000/mL
with brisk bleeding, regardless of the etiology of thrombocytopenia. In patients with acute menorrhagia and thrombocytopenia
undergoing procedures, platelet transfusion should be considered
if the platelet count is 50,000 and for major surgery if the platelet
count is 100,000.
2.6.3. Specic treatment for various thrombocytopenic conditions
In women with acute menorrhagia and ITP, specic treatment
is indicated in addition to platelet transfusion. This should include
intravenous immunoglobulin (IVIg) and initiation of corticosteroids [47]. For chemotherapy-induced complications, preventative
therapy for subsequent cycles of chemotherapy may include
gonadotropin-releasing hormone agonist maintenance to inhibit
the menstrual cycle and reduce bleeding [48]. For patients with
Glanzmanns thrombasthenia, platelet transfusions are considered rst-line treatment; however, if platelet transfusion
refractoriness develops, then evidence suggests that recombinant
factor VIIa (rFVIIa) is an alternative approach for cessation of
bleeding [49]. Similarly, rFVIIa may be an effective second-line
option in BernardSoulier disease [50]. Desmopressin may also be
effective in BernardSoulier disease, Glanzmanns thrombasthenia, and other platelet function disorders [51]. In cases of nonspecic platelet function disorder (i.e., non-specic platelet
aggregation and/or release abnormalities), desmopressin has
been shown to shorten the bleeding time in approximately 50% of
cases [51].

2.6.4. Management of acute menorrhagia in the patient with other

rare bleeding disorders
Rare bleeding disorders should also be considered in patients
presenting with acute menorrhagia, but any other contributing
factors will need to be investigated. It is important to consider
that cessation of menorrhagia in these patients may require
more treatment in terms of specic replacement therapy of the
decient coagulation protein than for cessation of other types of
bleeding.
Treatment should be as recommended for patients without a
diagnosed bleeding disorder but will include specic factor
replacement as necessary. Medical therapy should be regarded
as the rst choice of treatment as this may be the only option to
preserve reproductive function. At present, there are limited data
on prophylaxis of bleeding in these patients and on-demand
treatment to stop bleeding is of utmost importance. Where
possible, replacement should be achieved through the use of
concentrated coagulation factors vis-a`-vis the specic coagulation
factor deciency present. A number of single plasma-derived or
recombinant coagulation factors are available as well as prothrombin complex concentrates (PCCs) which are concentrates of a
number of coagulation factors, often containing three or four
clotting factors and antithrombotic agents such as protein C and S
(Tables 6 and 7) [5254]. Due to the large volume of fresh frozen
plasma (FFP) that is often required in massive hemorrhage (which
may lead to uid overload [52,55]) and due to the potential risk of
transmitted infection, FFP should only be used to treat factor
deciency if no specic factor concentrate is available, for example,
in factor V deciency [56].
It should be noted that patients with brinogen deciency,
including abrinogenemia and dysbrinogenemia, are at an
increased risk of thrombosis [57], and therefore hormonal therapy
and antibrinolytics should be used with caution until normal
brinogen levels are restored. In fact, antibrinolytics are contraindicated in the case of dysbrinogenemia. In these patients,
mechanical approaches such as balloon tamponade and contraceptive doses of a progestogen should be used before an estrogen or
combined hormonal therapy is prescribed.
2.7. Management of acute menorrhagia in the patient on
anticoagulation therapy
Despite the potential underlying risk of thrombosis in patients
receiving anticoagulation therapy, it is universally accepted that
reversal of anticoagulation should not be delayed in lifethreatening bleeding [52,58,59]. There are several guidelines
available which detail acceptable methods of anticoagulation
reversal. In cases of life-threatening bleeding, these recommend
that PCCs rather than FFP should be used in conjunction with
Table 6
Single-factor coagulation concentrates for replacement therapy in patients with
acute menorrhagia with clotting factor deciencies.
Factor

Brand

Company

Fibrinogen

Clottagen1
Fibrinogen HT1
FIBRORAAS1
Haemocomplettan P1/RiaSTAP1
Facteur VII-LFB1
Factor VII
NovoSeven1 (rFVIIa)
Factor X P Behring1
Factor XI
Hemoleven1
Fibrogammin1 P
rFXIII-A2a

LFB
Benesis
Shangai RAAS
CSL Behring
LFB
Baxter BioScience
Novo Nordisk
CSL Behring
BPL
LFB
CSL Behring
Novo Nordisk

FVII

FX
FXI
FXIII
a

Currently on Phase 3 clinical trial as hemostatic agent.

Please cite this article in press as: James AH, et al. Evaluation and management of acute menorrhagia in women with and without
underlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/
j.ejogrb.2011.04.025

Antithrombotic content
VII

IX

Protein C

ATIII label
(U/ml)

Heparin label
(U/ml)

Label
(U/ml)

Ratio
(%)

Label
(U/ml)

Ratio
(%)

Label
(U/ml)

Ratio
(%)

Label
(U/ml)

Ratio
(%)

C label
(U/ml)

S label
(U/ml)

Z label
(U/ml)

2048

133

1025

69

2031

100

2260

161

1545

1326

Not in label

0.21.5

0.42.0

1136

98

924

66

25

100

1830

96

731

732

Not in label

Not in label

Not in label

30

100

25

83

30

100

30

100

>20

Not in label

Not in label

0.751.5

<15

25
15

100
75

Not in label
5

25

25
20

100
100

25
15

100
75

Not in label
Not in label

Not in label
Not in label

Not in label
Not in label

3.75
Not in label

40

160

25

100

25

100

40

160

Not in label

Not in label

Not in label

Not in label
Present, not
quantied
Not in label

Uman Complex D.I. (Kedrion); Italy

25

100

Not in label

25

100

20

80

Not in label

Not in label

Not in label

PPSB-human SD/Nano (Octapharrna);

Germany
Prolnine (Grifola); USA
Bebulin (Baxter); USA

2555

130

7.520

45

2437.5

100

2555

130

2050

525

Not in label

Present, not
quantied
0.53

Present
Present

150

Present
Present (low)

35

Present
Present

100
100

Present
Present

100

Not in label
Not in label

Not in label
Not in label

Not in label
Not in label

Not in label
Not in label

Not in label

Not in label

Not in label

Not in label

Berjplex P/N (CSL Behring); major western

European countries
Octaplex (Octapharma); major western
European countries
Prothromplex Total/S-TIM 4 Immuno
(Baxter); Sweden, Germany, Austria
Prothromplex TIM 3 (Baxter); Italy, Austria
Cofac/PPSB SD (Sanquin/CAF); Netherlands,
Belgium, Austria, Germany
Kaakadil (LFB); France

FEIBA (Baxter): USA

Present,
not quantied
(nonactivated)

Present,
not quantied
(activated)

500, 1000,
or 2500 U per
vial
(nonactivated)

Present,
not quantied
(nonactivated)

Factor content ratios are based on the content of factor IX.

*In Europe, ranges are usually given on the product label, in accordance with the European Pharmacopoeia; single values are generally from older, national registrations.
PCC prothrombin complex concentrate.

Present,
not quantied
Present, not
quantied
0.56
Not present
0.15 U per U
of factor IX
Not present

G Model

Factor content
II

A.H. James et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology xxx (2011) xxxxxx

Product (manufacturer): international

availability

EURO-7311; No. of Pages 11

Please cite this article in press as: James AH, et al. Evaluation and management of acute menorrhagia in women with and without
underlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/
j.ejogrb.2011.04.025

Table 7
Constituents of commercially available prothrombin complex concentrates. Table reproduced from Levy et al. [54] with permission from the American Society of Anesthesiologists.

G Model

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A.H. James et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology xxx (2011) xxxxxx

vitamin K administered either intravenously or orally [52,58,59].

In these patients, however, it is often sufcient to stabilize bleeding
rather than achieve complete cessation, using the international
normalized ratio (INR), prothrombin time (PT) and activated
partial thromboplastin time (aPTT) as a guide. Mechanical
approaches (e.g., balloon tamponade) are preferred over antibrinolytics or hormones to stabilize the patient at risk of
thrombosis, due to the increased risk of thrombosis with these
agents.
In cases of severe menorrhagia, desmopressin [60] and/or
platelet transfusion could be considered for patients on antiplatelet therapy [61]. In hemodynamically unstable patients
receiving anti-platelet therapy, platelet transfusion should be
considered primarily [62]. The threshold at which platelet
transfusion would be considered for a patient on antiplatelet
therapy is dependent upon the clinical scenario, but transfusion
would certainly be considered during acute menorrhagia with a
platelet count <50,000/mL. Although these treatments can help to
improve bleeding, it is necessary to ensure that hemoglobin levels
are restored in order to reconstitute platelet function.
Mechanical thromboprophylaxis is recommended in patients
with a history of venous thromboembolism while the patient is not
receiving anticoagulation [63]. An inferior vena cava lter should
be considered in patients with a recent deep vein thrombosis or
pulmonary embolism whose anticoagulation must be held or
reversed [63]. Once the patient is stable, maintenance treatment
will be as for patients not receiving anticoagulation; however, due
to the increased risk of thrombosis in these patients, estrogens and
antibrinolytics are contraindicated. Furthermore, once the
patient is stable, full anticoagulation should be resumed, bridging
with intravenous unfractionated heparin or subcutaneous low
molecular weight heparin [58].
3. Future perspectives
Owing to the lack of available data on acute menorrhagia,
further studies are required to fully assess the epidemiology, risk
factors and treatments for acute menorrhagia. Many of the
recommendations for treatment are based on studies in chronic
menorrhagia, which may not be entirely indicative of the acute
condition. Epidemiological studies could generate prevalence data
on patients who present to the ED, require admission to hospital, or
otherwise require emergency treatment for acute menorrhagia (all
cause). Furthermore, prospective studies could, and should, be
designed to provide data on the risk factors for bleeding, e.g., to
examine whether low hemoglobin levels trigger bleeding (by
decreasing platelet aggregation, as red cells function as a scaffold
for platelet aggregation) and whether uremia is a risk factor for
bleeding. These could also help to elucidate the contribution of
multiple factors as causes of bleeding. While it would be ideal to
validate the suggested treatment protocols, treatment research is
difcult to undertake due to the ethical considerations for
randomized controlled trials in the acute setting; in this case,
extrapolation from studies in chronic menorrhagia may be more
appropriate. Comparison of management protocols used in a large
numbers of institutions could, however, provide valuable insights
into treatment outcomes.
4. Conclusions
Optimizing the management of acute menorrhagia remains of
clinical importance due to the life-threatening nature of the
condition. The wide variety of causes of the condition emphasize
the need to correctly evaluate the underlying causes and tailor
management accordingly. Future studies will help to further
elucidate treatment options.

Disclosure of interest
Dr. Andra James has received research support, honoraria and
served on Advisory Committees for CSL Behring and has received
honoraria from Grifols.
Dr. Peter Kouides has received research support and honoraria
from CSL Behring; he has served on Advisory Committees for CSL
Behring, Novo Nordisk, Baxter and Bayer and has acted as a
Consultant for Xanodyne Pharmaceuticals.
Dr. Rezan Abdul-Kadir has received honoraria from CSL Behring.
Dr. Jennifer E. Dietrich has received honoraria from CSL Behring
and Merck. She has served as a Consultant for CSL Behring and has
received research funding from Duramed Pharmaceuticals.
Dr. Mans Edlund has received honoraria from CSL Behring,
research support from Ferring and has acted as a Consultant for
Xanodyne Pharmaceuticals.
Dr. Augusto B. Federici has served on the Advisory Committees
of Baxter, CSL Behring, Grifols and Octapharma and received
honoraria from Baxter, CSL Behring, Grifols, Kedrion and Octapharma.
Dr. Susan Halimeh has received honoraria from CSL Behring.
Dr. Pieter Willem Kamphuisen is a consultant for CSL Behring
and has received research grants from Wyeth, Bayer and Novo
Nordisk.
Dr. Martinez-Perez has received honoraria for CSL Behring.
Dr. Lee has been the chairperson for two DSMBs for Novo
Nordisk and is a founding editor of the journal Haemophilia
published by Wiley Blackwell. She received travelling and hotel
expenses from CSL Behring.
Dr. Claire McLintock has received honoraria and served on
Advisory Committees for CSL Behring and Novo Nordisk and has
acted as a Consultant for Novo Nordisk.
Dr. Flora Peyvandi has received honoraria from Novo Nordisk
and CSL Behring.
Dr. Claire Philipp has received research support and honoraria
and served on advisory committee for CSL Behring.
Dr. Jeffrey Wilkinson has received honoraria from CSL Behring.
Dr. Rochelle Winikoff has received honoraria and served on
Advisory Committees for CSL Behring.
Contribution to authorship
All authors attended and presented at a consensus meeting held
on 1617 November 2009. All authors provided presentations that
were used as the basis of this consensus and fully contributed to
the discussions during the meeting and in the development of the
manuscript.
Funding
Financial support for the consensus meeting and paper was
provided by CSL Behring (Marburg, Germany).
Acknowledgements
Editorial support for this paper was provided by Fishawack
Communications.
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j.ejogrb.2011.04.025

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underlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/
j.ejogrb.2011.04.025

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Please cite this article in press as: James AH, et al. Evaluation and management of acute menorrhagia in women with and without
underlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/
j.ejogrb.2011.04.025