2011_06Artacute menorragiahalimeh

European Journal of Obstetrics & Gynecology and Reproductive Biology xxx (2011) xxxxxx

G Model

EURO-7311; No. of Pages 11

Contents lists available at ScienceDirect

European Journal of Obstetrics & Gynecology andReproductive BiologyReview

Evaluation and management of acute menorrhagia in women with and withoutunderlying 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 Philippm,Jeffrey Wilkinson n, Rochelle Winikoff o

aWomens Hemostasis and Thrombosis Clinic, Duke University Medical Center, Durham, NC, USAbMary M. Gooley Hemophilia Treatment Center, Rochester General Hospital, Rochester, NY, USAcDepartment of Obstetrics and Gynaecology, Royal Free Hospital, London, UKdDivision of Pediatric & Adolescent Gynecology, Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, TX, USAeDepartment of Obstetrics and & Gynecology, Danderyds University Hospital, Stockholm, SwedenfDivision of Hematology and Transfusion Medicine, Luigi Sacco University Hospital, Department of Internal Medicine, University of Milan, Milan, ItalygCentre for Coagulation Disorders Rhine-Ruhr Area, GermanyhDepartment of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlandsi Emeritus Professor, University of London, London, UKjDepartment Obstetrics and Gynecology, Fundacion Jimenez Diaz Hospital, Madrid, SpainkDepartment of OB/GYN, National Womens Health, Auckland City Hospital, Auckland, New ZealandlDepartment 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, ItalymDivision of Hematology, Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USAnObstetrics and Gynecology, Minimally Invasive Gynecologic Surgery, Duke University Medical Center, Durham, NC, USAoHemophilia Treatment Center, CHU Sainte-Justine, Montreal, Quebec, Canada

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

2.1. Results of PubMed search. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

2.2. Causes and predictors of acute menorrhagia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

2.3. Prevalence of hemostasis disorders in acute menorrhagia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

2.4. Evaluation of acute menorrhagia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

2.5. Optimal management strategies for acute menorrhagia in patients without a diagnosed bleeding disorder . . . . . . . . . . . . . . . . . . . 000

2.5.1. Hormonal treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

2.5.2. Antibrinolytic treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

A R T I C L E I N F O

Article history:

Received 5 October 2010

Received in revised form 25 February 2011

Accepted 30 April 2011

Keywords:

Acute menorrhagia

Bleeding disorder

Hemostasis management

Consensus

Coagulation factor

A B S T R A C T

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.

* Corresponding author. Tel.: +1 919 668 0011; fax: +1 919 681 7861.

E-mail address: [email protected] (A.H. James).

jou r nal h o mep ag e: w ww .e lsev ier . co m / loc ate /e jo g rb

0301-2115/$ see front matter 2011 Elsevier Ireland Ltd. All rights reserved.doi:10.1016/j.ejogrb.2011.04.025Please cite this article in press as: James AH, et al. Evaluation and management of acute menorrhagia in women with and withoutunderlying bleeding disorders: consensus from an international expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/j.ejogrb.2011.04.025

. .

. .

o

ith

ith

nd

ith

u

. .

. .

. .

. .

A.H. James et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology xxx (2011) xxxxxx2

G Model

EURO-7311; No. of Pages 11pertinent literature and evidence to guide the consensus. Theterms acute menorrhagia, menorrhagia and transfusion andsevere menorrhagia were entered with no restrictions placed onthe dates of the search or the type of article, to ensure that allpotential articles were identied. These terms were cross-referenced with von Willebrand disease, coagulation factordeciency and platelet function defect.

Acute menorrhagia has not previously been rigorouslydened. For the purpose of this consensus, the hematologyand obstetric and gynecology experts dened acute menorrhagiaas (1) life-threatening bleeding of uterine origin, (2) in theabsence of pregnancy or malignancy, (3) occurring in womenranging from teen to perimenopausal age, (4) with or withoutpreviously diagnosed bleeding disorders, (5) presenting to the

forties [11].

2.3. Prevalence of hemostasis disorders in acute menorrhagia

VWD is one of the most common bleeding disorders associatedwith menorrhagia, with an overall prevalence of 13% in womenpresenting with chronic menorrhagia [6]. In turn, 7492% ofwomen with VWD experience menorrhagia, with the actualprevalence dependent on the VWD type [1214]. Rare bleedingdisorders are also associated with menorrhagia. A review of theliterature on menorrhagia conducted in 2005 revealed a preva-lence of 3570% for women with deciencies of factor I, XI or XIII[15]. Factors II, V and X have also been associated with a highprevalence of bleeding [16].2.5.3. Surgical treatment . . . . . . . . . . . . . . . . . . . . . . . . . . .

2.5.4. Multidisciplinary management . . . . . . . . . . . . . . . . .

2.6. Management of acute menorrhagia in the patient with a hem

2.6.1. Management of acute menorrhagia in the patient w


2.6.3. Specic treatment for various thrombocytopenic co


2.7. Management of acute menorrhagia in the patient on anticoag

3. Future perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction

Menorrhagia is a gynecological condition which adverselyaffects quality of life for many women. Acute menorrhagia can bedened as excessive menstrual or inter-menstrual bleedingoccurring in a woman of childbearing age requiring emergencytreatment excluding pregnancy, postpartum hemorrhage, traumaand malignancy [1,2]. Menorrhagia is usually dened by bloodloss of over 80 mL per menstrual cycle, with anemia, low (belownormal) ferritin levels, passing clots greater than a 50 pence-coinin size (1.1 in. or 2.8 cm in diameter) [3], and soaking of bedclothes or through a pad or tampon within 1 h [3,4] also beingindicative of the condition. There are a variety of different causesof menorrhagia, and gynecological evaluation is essential to tailormanagement to the individual patient to prevent unnecessaryinvasive procedures which may have limited effect. Inheritedbleeding disorders have been linked to a signicant prevalence ofmenorrhagia [5], with von Willebrand disease (VWD), plateletfunction disorder and factor XI deciency exhibiting a particularlyhigh frequency [5,6]. The incidence and clinical signicance ofacute menorrhagia in women with underlying disorders ofhemostasis, however, are often underestimated. Furthermore,the lack of recent evidence for diagnostic and treatment strategiesin acute menorrhagia [7] necessitates the extrapolation fromevidence in chronic menorrhagia. Guidelines for the evaluationand management of chronic menorrhagia in patients with anunderlying disorder of hemostasis such as VWD were recentlypublished following a consensus meeting of experts in hematolo-gy and obstetrics and gynecology [4]. To address the lack ofguidance for the management of acute menorrhagia, a furthermeeting was held in November 2009 in London, UK, to reachconsensus on the evaluation and management of acute menor-rhagia particularly in the setting of an underlying disorder ofhemostasis.

2. Methods

An extensive PubMed search was conducted to identifyPlease cite this article in press as: James AH, et al. Evaluation and munderlying bleeding disorders: consensus from an internationaj.ejogrb.2011.04.025 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

stasis disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

VWD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

thrombocytopenia or a platelet function disorder. . . . . . . . . . . . . 000

itions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

other rare bleeding disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

lation therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

emergency department (ED), (6) with a need for immediateevaluation and treatment and (7) with potential need for bothhemostatic 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 observationalstudies. Randomized trials were found that addressed menor-rhagia, but only one small randomized trial was found thataddressed acute menorrhagia [8]. As a result, the recommenda-tions provided in this consensus are based on the opinions ofexperts.

2.2. Causes and predictors of acute menorrhagia

There are a number of causes of acute menorrhagia, rangingfrom pathologies including systemic disease and coagulationdisorders to anatomic conditions and treatment with somemedications [9]. The causes of relevance to these guidelines, andthe age groups which they affect, are shown in Fig. 1. Other causesthat fall outside the present denition of acute menorrhagiainclude pregnancy-related complications and gynecologic malig-nancy.

The most likely causes of acute menorrhagia are in partdetermined by the age of the patient. Since the rst clinicalmanifestation of menorrhagia is often related to the onset ofmenarche, underlying causes are seldom identied beforeadolescence [10]. Together with anovulatory bleeding, unidenti-ed bleeding disorders are commonly associated with acutemenorrhagia in this age range [9]. As the age of women increases,those suffering from acute menorrhagia with a history ofunderlying bleeding disorders may experience acute bleedingepisodes due to continued sub-optimal management. Conversely,acute menorrhagia occurring as a result of local pathology such asbroids or endometrial polyps is often not observed until womenreach their mid-thirties [9]; perimenopausal anovulatory bleed-ing is usually not observed until women reach their mid to lateanagement of acute menorrhagia in women with and withoutl expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/

There are few prevalence studies of platelet disorders, includingthrombocytopenic as well as thrombocytopathic disorders, in thesetting of acute menorrhagia [17], and their prevalence may beunderestimated. Studies of menorrhagia have identied a number

of both inherited and acquired platelet disorders associated withthe condition [1822]. Based on the limited reports available,immune thrombocytopenic purpura (ITP) may be one of the mostcommon causes of acute menorrhagia in adolescents [23]. As for

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 availableliterature [25,6971] and authors professional opinion/experience.

Table 1Evaluation of acute menorrhagia.

Patient history * Menstrual* Medical

leed

edi

ecen

lood

eart

espi

A.H. James et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology xxx (2011) xxxxxx 3

G Model

EURO-7311; No. of Pages 11* B* M* R

Vital signs * B* H* R

* Oxyg

Speculum and pelvic examinations * Depe* Depe

a mea

to tra

* Pap s* Endom

Laboratory tests Immedia

* Comp* Blood* Pregn* Partia* Activ* Fibrin* VWF

proce

* Plasmstorag

Addition

* Serum* Liver * Full h

(i.e., p

* Platel* Facto* Fibrin* Thyro

Ultrasound * Depeand t

* Intrav

a 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 munderlying bleeding disorders: consensus from an internationaj.ejogrb.2011.04.025ing

cation, including use of hormonal contraceptives

t trauma

pressure

rate

ration rateen saturation

nding on the age of the patient and the clinicians judgment

nding on the availability of the testing, the feasibility of obtaining

ningful specimen in the setting of ooding and the ability

ck the results

mear

etrial biopsy

te:

lete blood count

type and cross-match

ancy test

l thromboplastin time (PTT)

ated partial thromboplastin time (aPTT)

ogen level

levels (depending on availability for real-time analysis and appropriate

ssing) [64,65] a

a sample for storage (refer to suitable guidelines on the handling and

e of plasma sample) [66]

al:

iron, total iron binding capacity and ferritin

function

emostatic evaluation including the following tests if indicated

ast personal or family history to suggest an underlying disorder of hemostasis)

et aggregation and release studies (cannot be done at time of acute event)

r IX, XI and XIII

olysis

id stimulating hormone (TSH)

nding on clinical judgment (based on diagnostic suspicion

he age of the patient, and availability of equipment)

aginal ultrasound (depending on whether the patient has been sexually active)

].

anagement of acute menorrhagia in women with and withoutl expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/

the prevalence of thrombocytopathic disorders in chronic menor-rhagia, Philipp et al. reported that approximately half of patientspresenting with unexplained menorrhagia had a defect in plateletaggregation and/or release [24,25].

2.4. Evaluation of acute menorrhagia

There was consensus that it is important to establish a diagnosisfor and underlying cause of the abnormal bleeding, as this will helpto ensure appropriate management of the bleeding and potentiallyprevent further bleeding. The experts also reached a consensus onhow patients presenting with acute menorrhagia should bemanaged. The recommended evaluation is summarized in Table1. The evaluation comprises a combination of patient history,including any family history (although lack of this should notexclude a diagnosis of an inherited disorder), ultrasound imaging,laboratory tests and speculum and pelvic examination. Dependingon the accessibility of testing, the feasibility of achieving ameaningful specimen in the setting of acute menorrhagia and theability to track the results from the ED, the provider may want toconsider obtaining a Pap smear and endometrial biopsy at the timeof examination. Otherwise, these tests can be postponed until thepatient is stable and suitable follow-up provision is available.Testing of hormone levels, while potentially useful in theevaluation of continuing menorrhagia, is not essential in theevaluation of acute menorrhagia and can also be postponed. Due tothe difculties in obtaining some of the coagulation tests, theremay be a tendency to withhold further evaluation; this can greatlyimpact on patient care. A number of studies and other consensusgroups have highlighted the ongoing need to consider underlyingbleeding disorders, especially in adolescents presenting with acutemenorrhagia [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 havebeen devised previously and these were considered during thedevelopment of this consensus [26]. A range of rst-line treatmentoptions was devised (Table 2); the order of use and whether theyshould be used alone or in combination is dependent on clinicaljudgment and social and cultural aspects. The options for rst-linetherapy include hormonal, surgical, and hemostatic treatments.

2.5.1. Hormonal treatment

The suggested regimens for the administration of hormonalpreparations in acutely bleeding patients are detailed in Table 3.Once the patient has been stabilized, these regimens should betapered 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 commonlyused antibrinolytic agents. Although aminocaproic acid is stillused in certain countries to treat acute bleeding, it has been largelyreplaced by tranexamic acid in countries where this is available.Therefore, the following discussion will focus principally ontranexamic acid. Tranexamic acid is used widely in the treatmentand prophylaxis of mucous membrane and post-surgical bleeding;it is an effective rst-line treatment for menorrhagia [28]. As asynthetic derivative of the amino acid lysine, tranexamic acidexerts its antibrinolytic effect through the reversible blockade oflysine-binding sites on plasminogen molecules. Both intravenous(IV) and oral formulations are available, although the oral form isnot currently available in some countries. The IV formulation has a

dis

] i

he

, a

th

bu

ici

ea

ar

(M

pla

r

ry

e

e

ve

ry


G Model

EURO-7311; No. of Pages 11Table 2Treatment options for acute menorrhagia in patients without a diagnosed bleeding

First line antibrinolytic agents hormonal agents (intravenous Premarin1 [Pzer Inc, New York, New York, USA balloon tamponade this technique may provide a temporary measure to limit bleeding while furt

operating room or theatre

the use of this as a rst-line treatment would depend on the patient (e.g. agesetting (such as availability of antibrinolytics and hormonal agents and whe

Second line (depending on the desire for future fertility) dilation and curettage (D & C), which would be rarely indicated in adolescents,

This would be accompanied by a hysteroscopy if there is a high degree of susp

endometrial ablation, if no desire for future fertility uterine artery embolization, if no desire for future fertility or as a life-saving m recombinant factor VIIa (rFVIIa), which would be considered if the patient is ne hysterectomy

Maintenance therapy (once stabilized) hormonal agents combined hormonal contraceptives progestin only contraceptives including the levonorgestrel intrauterine device

(Depo-Provera1 [Pzer Inc, New York, New York, USA]) and the Implanon1 im

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

Hormone Route Protocol fo

Conjugated oestrogens IV 25 mg eve

30 mg ethinyl estradiol/0.3 mg norgestrel(or other 30 mg combination pill)

Oral One tablet

50 mg ethinyl estradiol/0.5 mg norgestrel(or other 50 mg combination pill)

Oral One tablet

Norethindrone acetate Oral 510 mg e

Medroxyprogesterone Oral 10 mg eve

IV, intravenous.Please cite this article in press as: James AH, et al. Evaluation and munderlying bleeding disorders: consensus from an internationaj.ejogrb.2011.04.025order [8,7077].

f available)

r investigations are carried out or the patient is undergoing transfer to the

bility to tolerate a pelvic examination), suspected pathology and the clinical

er the patient is hemodynamically unstable)

t this technique has value if a tissue sample is needed for diagnosis.

on of pathology (e.g. polyp)

sure

death in an attempt to preserve the uterus and life

irena1 [Bayer Corporation, Leverkusen, Germany], injections

nt (Schering-Plough, Kenilworth, NJ, USA)

acute menstrual cessation

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

very 6 h until bleeding stops, consider re-evaluating at 48 h

very 6 h until bleeding stops, consider re-evaluating at 48 h

ry 4 h

4 h (and up to 80 mg/day)anagement of acute menorrhagia in women with and withoutl expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/

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

Hormone Tapering regimens

50 mg combination hormonalcontraceptive pill

May begin with this every 6 h ora

for 2 days and up to 7 days, then

thereafter. If transitioning from IV

or even every 8 h, then follow as

3035 mg combinationhormonal contraceptive pill

May begin with this every 6 h ora

then every 12 h for 2 days and up

Norethindrone acetate 510 mg every 4 h orally until ble

3 days, then every 12 h for 2 days

meg

0 m

ry 1

init


G Model

EURO-7311; No. of Pages 11faster onset of action and so may be more appropriate in somecases of acute menorrhagia. Tranexamic acid is contraindicated inpatients with disseminated intravascular coagulation, venous orarterial thromboembolism, macroscopic hematuria or colorblindness. Side-effects are uncommon but typically manifest asnausea and dizziness which respond to reductions in dose. Whileprolonged treatment may increase thrombotic tendency, large-scale studies have revealed that the incidence of thrombosis inwomen treated with tranexamic acid is similar to the spontaneousincidence of thrombosis in untreated women [2931].

The usual IV dose of tranexamic acid is 10 mg/kg every 8 h andthe usual oral dose is 2025 mg/kg every 8 h. Various other dosingregimens are available for the oral formulation and these are listedin Table 5. No single dosing regimen has been demonstrated to besuperior, although higher doses (3 g daily) may be more effective inacute menorrhagia than lower doses (2 g daily) [32]. In the UnitedStates, a new oral sustained formulation has recently beenapproved (dosed at two tablets of 650 mg each 1.3 g) orally threetimes per day [33]. (Neither this formulation nor this dose wasstudied in the treatment of acute menorrhagia.) Treatmentduration is usually tailored according to clinical bleeding andmay be stopped without tapering when heavy menstrual bleedingsubsides.

2.5.3. Surgical treatment

When medical therapy fails in the treatment of acutemenorrhagia, or if the patient has contraindications to medicalmanagement (i.e., thromboembolic disease), surgical managementoptions must be considered. The choice of the surgical procedure isdictated by the suspected etiology and the desire for maintainingfertility after the procedure. Those procedures that can sparefertility include: dilatation and curettage (D & C), hysteroscopy

after initial bleeding stops if

Medroxyprogesterone 10 mg every 4 h orally (max 8

every 8 h for 3 days, then eve

May switch over to this after

IV, intravenous.with D & C, hysteroscopy with polypectomy or myomectomy andendometrial balloon tamponade.

Endometrial balloon tamponade can be an effective means ofcontrolling acute menorrhagia and allowing stabilization of thepatient in anticipation of further medical (hemostatic, hormonal)therapy or other surgical procedures. In a uterus less than 12

Table 5Doses 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

Please cite this article in press as: James AH, et al. Evaluation and munderlying bleeding disorders: consensus from an internationaj.ejogrb.2011.04.025weeks size, a Foley catheter with a 30 cc balloon can be insertedthrough the cervix and inated with saline until resistance of themyometrium is felt. Ultrasound can be helpful to diagnoseintrauterine pathology, to conrm adequate placement anddistension and to exclude ongoing bleeding above the balloon [34].

Uterine artery embolization (UAE) has been successful in thecontrol of acute menorrhagia [35]. The aorta is accessed via thefemoral artery, a pelvic angiogram is obtained, bleeding vessels areidentied and then occluded [36]. The procedure entails inherentdelay in transferring the patient to the angiography suite,preparing the patient and performing the procedure, and it mustbe regarded as second line therapy [36]. While successfulpregnancies have been reported after this procedure [37], ratesof pregnancy complications are increased after UAE and futurefertility is still generally considered a contraindication to thisprocedure. Loss of ovarian function (transient or permanent) dueto embolization of utero-ovarian collaterals can occur after UAE,leading to premature menopause. The risk of this complication isage-related and reported to be 12% in women younger than 45years [28]; thus, this option should only be used as a life-savingmeasure in young women. Endometrial ablation has beendemonstrated to be an effective means of controlling acute menorrhagia and has been proposed as an alternative to hysterectomyin women who are poor surgical candidates [38]. However, it stillrequires a minimum of local anesthesia or intravenous sedation,must be performed in the operating room or theater, should not beperformed when malignancy has not been excluded and may notbe successful in the presence of severe bleeding [39,40]. Pregnancyis contraindicated in women who have had endometrial ablation.

Hysterectomy is the most denitive surgical treatment ofmenorrhagia, but can often be avoided by employing one or moreof the above measures. In a patient with acute, life-threatening

lly until bleeding stops, then decrease to every 8 h

every 12 h for 2 days and up to 7 days, then daily

Premarin, may step down to 50 mg pill every 6 habove.

lly until bleeding stops, then decrease to every 8 h for 2 days and up to 7 days,

to 7 days, then daily thereafter.

eding stops, then every 6 h for 4 days, then every 8 h for

to 2 weeks, then daily thereafter. May switch over to this

estrol acetate utilised for acute menstrual control.

g) until bleeding stops, then every 6 h for 4 days, then

2 h for 2 days to 2 weeks, then daily thereafter.

ial bleeding stops if megestrol acetate utilised for acute menstrual control.hemorrhage, hysterectomy should not be delayed in favor ofpotentially less effective measures, especially if fertility is nolonger desired or possible.

2.5.4. Multidisciplinary management

Multidisciplinary management of acute menorrhagia betweengynecology, hematology, pharmacy and nursing staff can greatlybenet patient care. A sample care plan that ensures appropriateorchestration of these elements is presented in Fig. 2. This plan is inuse at Sainte-Justine Hospital, Montreal, Canada, and has had apositive impact both on the success of controlling heavy bleedingand on improving the quality of care provided to women withacute menorrhagia [41]. It has also been associated with otherbenets such as increased investigation for bleeding disorders,more consistent use of antibrinolytic agents, fewer surgicalinterventions and fewer blood transfusions in adolescentspresenting with acute menorrhagia. Such a care plan can be



G Model

EURO-7311; No. of Pages 11modied to suit institutional requirements and should conform tousual 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 menorrha-gia in the patient with a disorder of hemostasis is generally asdescribed above with specics as described below. Measures tocontrol uterine bleeding should be implemented while correctingdeciencies of clotting factors or abnormalities of plateletnumber or function. The relative importance of hemostatic,

Fig. 2. Sample care plan from the CHU Sa

Please cite this article in press as: James AH, et al. Evaluation and munderlying bleeding disorders: consensus from an internationaj.ejogrb.2011.04.025hormonal and surgical treatment options will vary in eachclinical situation. When bleeding is uncontrolled and othertreatment options (hormonal therapy or antibrinolytics) eitherhave not yet been initiated or have not successfully elicited areduction in bleeding, we recommend endometrial balloontamponade with concomitant or subsequent hormonal and/orhemostatic therapy.

2.6.1. Management of acute menorrhagia in the patient with VWD

There are specic considerations for the rst-line treatment ofacute menorrhagia in patients with VWD which combinetreatment options. Desmopressin must be used with caution, if

inte-Justine, Montreal, Canada [42].


2.6.4. Management of acute menorrhagia in the patient with other

rare bleeding disorders

Rare bleeding disorders should also be considered in patientspresenting with acute menorrhagia, but any other contributingfactors will need to be investigated. It is important to considerthat cessation of menorrhagia in these patients may requiremore treatment in terms of specic replacement therapy of thedecient coagulation protein than for cessation of other types ofbleeding.

Treatment should be as recommended for patients without adiagnosed bleeding disorder but will include specic factorreplacement as necessary. Medical therapy should be regardedas the rst choice of treatment as this may be the only option topreserve reproductive function. At present, there are limited dataon prophylaxis of bleeding in these patients and on-demandtreatment to stop bleeding is of utmost importance. Where


G Model

EURO-7311; No. of Pages 11at all, in cases of massive hemorrhage. Desmopressin causes uidretention and patients receiving desmopressin should be uidrestricted, yet patients with acute menorrhagia commonly receiveat least 12 L of uid at the time of initial resuscitation. In theabsence of massive hemorrhage, the recommendation for rst-linetreatment of acute menorrhagia in patients with VWD isdesmopressin, which is frequently used in combination with anantibrinolytic agent such as tranexamic acid (both for 23 days,then tranexamic acid alone for 34 days). This is based on a reportthat desmopressin and tranexamic acid together are more effectivethan either agent alone [43] with the presumption that acutemenorrhagia is a clinical situation requiring as effective and rapid aresponse to hemostatic therapy as possible. Ideally, this approachshould only be used in patients who have demonstrated a priorresponse to desmopressin (dened as a doubling of the VWF levels[14] and minimum VWF response of 50%) and in whom uidoverload would not be an issue. Factor concentrates (e.g.,Haemate1 P/Humate1-P, CSL Behring, Marburg, Germany; Opti-vate1, Bio Products Laboratory, Elstree, UK; Alphanate1, Grifols UKLtd., Cambridge, UK; and Wilate1, Octapharma, Lachen,Switzerland) are available [44] for VWF and FVIII replacementand these should be used if desmopressin is contraindicated; forexample, in patients with no prior response (although if on-sitereal-time VWF analysis is available, one could conceivablymeasure post-desmopressin VWF levels 15 min post-infusion),in patients with potential for uid overload, in patients withongoing bleeding, in patients who are undergoing surgery [45] orin patients who are hemodynamically unstable. Maintenancetherapy in patients with VWD should be the same as recom-mended above for patients without a diagnosed bleeding disorder.Intranasal or oral desmopressin, where available, could be added toaugment 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 underlyingthrombocytopenia or a platelet function disorder should includemanagement of the underlying disorder. Platelet transfusionshould be considered rst-line therapy in patients with acutemenorrhagia and a platelet count

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

Product (manufacturer): international

availability

Factor content Antithrombotic content

II VII IX X 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)

Berjplex P/N (CSL Behring); major western

European countries

2048 133 1025 69 2031 100 2260 161 1545 1326 Not in label 0.21.5 0.42.0

Octaplex (Octapharma); major western

European countries

1136 98 924 66 25 100 1830 96 731 732 Not in label Not in label Not in label

Prothromplex Total/S-TIM 4 Immuno

(Baxter); Sweden, Germany, Austria

30 100 25 83 30 100 30 100 >20 Not in label Not in label 0.751.5


G Model

EURO-7311; No. of Pages 11vitamin K administered either intravenously or orally [52,58,59].In these patients, however, it is often sufcient to stabilize bleedingrather than achieve complete cessation, using the internationalnormalized ratio (INR), prothrombin time (PT) and activatedpartial thromboplastin time (aPTT) as a guide. Mechanicalapproaches (e.g., balloon tamponade) are preferred over anti-brinolytics or hormones to stabilize the patient at risk ofthrombosis, due to the increased risk of thrombosis with theseagents.

In cases of severe menorrhagia, desmopressin [60] and/orplatelet transfusion could be considered for patients on anti-platelet therapy [61]. In hemodynamically unstable patientsreceiving anti-platelet therapy, platelet transfusion should beconsidered primarily [62]. The threshold at which platelettransfusion would be considered for a patient on antiplatelettherapy is dependent upon the clinical scenario, but transfusionwould certainly be considered during acute menorrhagia with aplatelet count


G Model

EURO-7311; No. of Pages 11women with heavy periods: a survey with follow-up data. Am J Obstet Gynecol2004;190:121623.

[4] James AH, Kouides PA, Abdul-Kadir R, Edlund M, Federici AB, Halimeh S, et al.Von Willebrand disease and other bleeding disorders in women: consensus ondiagnosis and management from an international expert panel. Am J ObstetGynecol 2009;201(12):e18.

[5] Lee CA. Women and inherited bleeding disorders: menstrual issues. SeminHematol 1999;36:217.

[6] Shankar M, Lee CA, Sabin CA, Economides DL, Kadir RA. von Willebrand diseasein women with menorrhagia: a systematic review. BJOG 2004;111:73440.

[7] Claessens EA, Cowell CA. Acute adolescent menorrhagia. Am J Obstet Gynecol1981;139:27780.

[8] DeVore GR, Owens O, Kase N. Use of intravenous Premarin in the treatment ofdysfunctional uterine bleeding a double-blind randomized control study.Obstet Gynecol 1982;59:28591.

[9] Purcell JS, Hergenroeder AC. Severe Menorrhagia. Adolesc Med 1996;7:44954.

[10] Kadir RA, Economides DL, Sabin CA, Owens D, Lee CA. Frequency of inheritedbleeding disorders in women with menorrhagia. Lancet 1998;351:4859.

[11] McKinlay SM, Brambilla DJ, Posner JG. The normal menopause transition.Maturitas 2008;61:416.

[12] Kadir RA, Economides DL, Sabin CA, Pollard D, Lee CA. Assessment of menstrualblood loss and gynaecological problems in patients with inherited bleedingdisorders. Haemophilia 1999;5:408.

[13] Kouides PA, Phatak PD, Burkart P, Braggins C, Cox C, Bernstein Z, et al.Gynaecological and obstetrical morbidity in women with type I von Will-ebrand disease: results of a patient survey. Haemophilia 2000;6:6438.

[14] Ragni MV, Bontempo FA, Hassett AC. von Willebrand disease and bleeding inwomen. Haemophilia 1999;5:3137.

[15] James AH. More than menorrhagia: a review of the obstetric and gynaecolo-gical manifestations of bleeding disorders. Haemophilia 2005;11:295307.

[16] Lukes AS, Kadir RA, Peyvandi F, Kouides PA. Disorders of hemostasis andexcessive menstrual bleeding: prevalence and clinical impact. Fertil Steril2005;84:133844.

[17] Bevan JA, Maloney KW, Hillery CA, Gill JC, Montgomery RR, Scott JP. Bleedingdisorders: a common cause of menorrhagia in adolescents. J Pediatr2001;138:85661.

[18] Lopez JA, Andrews RK, Afshar-Kharghan V, Berndt MC. BernardSoulier syn-drome. Blood 1998;91:4397418.

[19] Markovitch O, Ellis M, Holzinger M, Goldberger S, Beyth Y. Severe juvenilevaginal bleeding due to Glanzmanns thrombasthenia: case report and reviewof the literature. Am J Hematol 1998;57:2257.

[20] Vijapurkar M, Mota L, Shetty S, Ghosh K. Menorrhagia and reproductive healthin rare bleeding disorders: a study from the Indian subcontinent. Haemophilia2009;15:199202.

[21] Levens ED, Scheinberg P, DeCherney AH. Severe menorrhagia associated withthrombocytopenia. Obstet Gynecol 2007;110:9137.

[22] Berger M, Brass LF. Severe thrombocytopenia in iron deciency anemia. Am JHematol 1987;24:4258.

[23] Claessens EA, Cowell CA. Dysfunctional uterine bleeding in the adolescent.Pediatr Clin North Am 1981;28:36978.

[24] Philipp CS, Dilley A, Miller CH, Evatt B, Baranwal A, Schwartz R, et al. Plateletfunctional defects in women with unexplained menorrhagia. J Thromb Hae-most 2003;1:47784.

[25] Philipp CS, Faiz A, Dowling N, Dilley A, Michaels LA, Ayers C, et al. Age and theprevalence of bleeding disorders in women with menorrhagia. Obstet Gynecol2005;105:616.

[26] Ely JW, Kennedy CM, Clark EC, Bowdler NC. Abnormal uterine bleeding: amanagement algorithm. J Am Board Fam Med 2006;19:590602.

[27] Perlman S, Nakajima S, Hertweck S. Clinical protocols in pediatric and adoles-cent gynecology: Informa; 2004.

[28] Tulandi T, Salamah K. Fertility and uterine artery embolization. Obstet Gynecol2010;115:85760.

[29] Husted H, Blond L, Sonne-Holm S, Holm G, Jacobsen TW, Gebuhr P. Tranexamicacid reduces blood loss and blood transfusions in primary total hip arthro-plasty: a prospective randomized double-blind study in 40 patients. ActaOrthop Scand 2003;74:6659.

[30] Lethaby A, Farquhar C, Cooke I. Antibrinolytics for heavy menstrual bleeding.Cochrane Database Syst Rev 2000;CD000249.

[31] Lozano M, Basora M, Peidro L, Merino I, Segur JM, Pereira A, et al. Effectivenessand safety of tranexamic acid administration during total knee arthroplasty.Vox Sang 2008;95:3944.

[32] Mohri H. High dose of tranexamic acid for treatment of severe menorrhagia inpatients with von Willebrand disease. J Thromb Thrombolysis 2002;14:2557.

[33] Lukes A, Gersten J, Shangold G, Patrick D, Moore K. A novel, oral tranexamicacid formulation for heavy menstrual bleeding: effect on quality of life.American College of Obstetrics and Gynecology; 2010.

[34] Hamani Y, Ben-Shachar I, Kalish Y, Porat S. Intrauterine balloon tamponade asa treatment for immune thrombocytopenic purpura-induced severe uterinebleeding. Fertil Steril 2010;8 [Epub June].

[35] Bowkley CW, Dubel GJ, Haas RA, Soares GM, Ahn SH. Uterine artery emboli-zation for control of life-threatening hemorrhage at menarche: brief report.JVasc Interv Radiol 2007;18:12731.

[36] Vedantham S, Goodwin SC, McLucas B, Mohr G. Uterine artery embolization:an underused method of controlling pelvic hemorrhage. Am J Obstet Gynecol1997;176:93848.Please cite this article in press as: James AH, et al. Evaluation and munderlying bleeding disorders: consensus from an internationaj.ejogrb.2011.04.025[37] Firouznia K, Ghanaati H, Sanaati M, Jalali AH, Shakiba M. Pregnancy afteruterine artery embolization for symptomatic broids: a series of 15 pregnan-cies. AJR Am J Roentgenol 2009;192:158892.

[38] Yeasmin S, Nakayama K, Ishibashi M, Katagiri A, Iida K, Nakayama N, et al.Microwave endometrial ablation as an alternative to hysterectomy for theemergent control of uterine bleeding in patients who are poor surgicalcandidates. Arch Gynecol Obstet 2009;280:27982.

[39] American College of Obstetricians and Gynecologists. Endometrial ablation.ACOG Pract Bull 2007;81.

[40] Nichols C, Gill E. Thermal balloon endometrial ablation for management ofacute uterine hemorrhage. Am Coll Obstet Gynecol 2002;100:10924.

[41] Winikoff R. Unpublished observation.[42] Wunder G, Francoeur D, Gascon S, Winikoff R. Has the introduction of a

standardized treatment protocol changed the management and outcomeof acute severe adolescent menorrhagia? Thromb Res 2009;123(Suppl.2):S150.

[43] Edlund M, Blomback M, Fried G. Desmopressin in the treatment of menorrha-gia in women with no common coagulation factor deciency but with pro-longed bleeding time. Blood Coagul Fibrinolysis 2002;13:22531.

[44] Federici AB, Castaman G, Thompson A, Berntorp E. von Willebrands disease:clinical management. Haemophilia 2006;12(Suppl. 3):1528.

[45] Kouides PA. Personal communication, 2009.[46] Kouides PA, Byams VR, Philipp CS, Stein SF, Heit JA, Lukes AS, et al. Multisite

management study of menorrhagia with abnormal laboratory haemostasis: aprospective crossover study of intranasal desmopressin and oral tranexamicacid. Br J Haematol 2009;145:21220.

[47] Godeau B, Provan D, Bussel J. Immune thrombocytopenic purpura in adults.Curr Opin Hematol 2007;14:53556.

[48] Meirow D, Rabinovici J, Katz D, Or R, Shufaro Y, Ben-Yehuda D. Prevention ofsevere menorrhagia in oncology patients with treatment-induced thrombo-cytopenia by luteinizing hormone-releasing hormone agonist and depo-medroxyprogesterone acetate. Cancer 2006;107:163441.

[49] Nurden AT. Glanzmann thrombasthenia. Orphanet J Rare Dis 2006;1:10.[50] Ozelo MC, Svirin P, Larina L. Use of recombinant factor VIIa in the management

of severe bleeding episodes in patients with BernardSoulier syndrome. AnnHematol 2005;84:81622.

[51] DiMichele DM, Hathaway WE. Use of DDAVP in inherited and acquired plateletdysfunction. Am J Hematol 1990;33:3945.

[52] Vigue B. Bench-to-bedside review: optimising emergency reversal of vitaminK antagonists in severe haemorrhage from theory to practice. Crit Care2009;13:209.

[53] Kalina U, Bickhard H, Schulte S. Biochemical comparison of seven commer-cially available prothrombin complex concentrates. Int J Clin Pract 2008;62:161422.

[54] Levy JH, Tanaka KA, Dietrich W. Perioperative hemostatic management ofpatients treated with vitamin K antagonists. Anesthesiology 2008;109:91826.

[55] Bux J. Transfusion-related acute lung injury (TRALI): a serious adverse event ofblood transfusion. Vox Sang 2005;89:110.

[56] Bennett K, Daley ML, Pike C. Factor V deciency and menstruation: a gyneco-logic challenge. Obstet Gynecol 1997;89:83940.

[57] Dupuy E, Soria C, Molho P, Zini JM, Rosenstingl S, Laurian C, et al. Embolizedischemic lesions of toes in an abrinogenemic patient: possible relevance to invivo circulating thrombin. Thromb Res 2001;102:2119.

[58] Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology andmanagement of the vitamin K antagonists: American College of Chest Physi-cians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest2008;133:160S98S.

[59] Spahn DR, Cerny V, Coats TJ, Duranteau J, Fernandez-Mondejar E, Gordini G,et al. Management of bleeding following major trauma: a European guideline.Crit Care 2007;11:R17.

[60] Leithauser B, Zielske D, Seyfert UT, Jung F. Effects of desmopressin on plateletmembrane glycoproteins and platelet aggregation in volunteers on clopido-grel. Clin Hemorheol Microcirc 2008;39:293302.

[61] Cattaneo M. Desmopressin in the treatment of patients with defects of plateletfunction. Haematologica 2002;87:11224.

[62] Vilahur G, Choi BG, Zafar MU, Viles-Gonzalez JF, Vorchheimer DA, Fuster V,et al. Normalization of platelet reactivity in clopidogrel-treated subjects.JThromb Haemost 2007;5:8290.

[63] Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ. Antith-rombotic therapy for venous thromboembolic disease: American College ofChest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).Chest 2008;133:454S545S.

[64] Bohm M, Taschner S, Kretzschmar E, Gerlach R, Favaloro EJ, Scharrer I. Coldstorage of citrated whole blood induces drastic time-dependent losses infactor VIII and von Willebrand factor: potential for misdiagnosis of haemo-philia and von Willebrand disease. Blood Coagul Fibrinolysis 2006;17:3945.

[65] Lipton RA. Misdiagnosis by milk box. Haemophilia 2003;9:235.[66] Nichols WL, Hultin MB, James AH, Manco-Johnson MJ, Montgomery RR, Ortel

TL, et al. von Willebrand disease (VWD): evidence-based diagnosis andmanagement guidelines, the National Heart, Lung, and Blood Institute (NHLBI)Expert Panel report (USA). Haemophilia 2008;14:171232.

[67] Kadir RA, Economides DL, Sabin CA, Owens D, Lee CA. Variations in coagulationfactors in women: effects of age, ethnicity, menstrual cycle and combined oralcontraceptive. Thromb Haemost 1999;82:145661.anagement of acute menorrhagia in women with and withoutl expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/

[68] Prescribing information for LYSTEDA. Available at http://www.xanodyne.com/pdf/Lysteda.pdf. Available from: http://www.xanodyne.com/pdf/Lysteda.pdf[accessed 7 May].

[69] Chen YC, Chao TY, Cheng SN, Hu SH, Liu JY. Prevalence of von Willebranddisease in women with iron deciency anaemia and menorrhagia in Taiwan.Haemophilia 2008;14:76874.

[70] Gupta S, Jose J, Manyonda I. Clinical presentation of broids. Best Pract Res ClinObstet Gynaecol 2008;22:61526.

[71] Palep-Singh M, Prentice A. Epidemiology of abnormal uterine bleeding. BestPract Res Clin Obstet Gynaecol 2007;21:88790.

[72] Fraser IS, Porte RJ, Kouides PA, Lukes AS. A benet-risk review of systemichaemostatic agents: part 2: in excessive or heavy menstrual bleeding. Drug Saf2008;31:27582.

[73] Chigbu CO, Iloabachie GC. Intrauterine Foley urethral catheter for postmyo-mectomy uterine bleeding. Int J Gynaecol Obstet 2006;95:1756.

[74] Georgiou C. Balloon tamponade in the management of postpartum haemor-rhage: a review. BJOG 2009;116:74857.

[75] Hurley VA, Beischer NA. Cervical pregnancy: hysterectomy avoided with theuse of a large Foley catheter balloon. Aust N Z J Obstet Gynaecol 1988;28:2302.

[76] Phelan 2nd JT, Broder J, Kouides PA. Near-fatal uterine hemorrhage duringinduction chemotherapy for acute myeloid leukemia: a case report of bilateraluterine artery embolization. Am J Hematol 2004;77:1515.

[77] Vidarsson B, Onundarson PT. Recombinant factor VIIa for bleeding in refrac-tory thrombocytopenia. Thromb Haemost 2000;83:6345.


G Model

EURO-7311; No. of Pages 11Please cite this article in press as: James AH, et al. Evaluation and munderlying bleeding disorders: consensus from an internationaj.ejogrb.2011.04.025anagement of acute menorrhagia in women with and withoutl expert panel. Eur J Obstet Gynecol (2011), doi:10.1016/

Evaluation and management of acute menorrhagia in women with and without underlying bleeding disorders: consensus from an ...1 Introduction2 Methods2.1 Results of PubMed search2.2 Causes and predictors of acute menorrhagia2.3 Prevalence of hemostasis disorders in acute menorrhagia2.4 Evaluation of acute menorrhagia2.5 Optimal management strategies for acute menorrhagia in patients without a diagnosed bleeding disorder2.5.1 Hormonal treatment2.5.2 Antifibrinolytic treatment2.5.3 Surgical treatment2.5.4 Multidisciplinary management

2.6 Management of acute menorrhagia in the patient with a hemostasis disorder2.6.1 Management of acute menorrhagia in the patient with VWD2.6.2 Management of acute menorrhagia in the patient with thrombocytopenia or a platelet function disorder2.6.3 Specific treatment for various thrombocytopenic conditions2.6.4 Management of acute menorrhagia in the patient with other rare bleeding disorders

2.7 Management of acute menorrhagia in the patient on anticoagulation therapy

3 Future perspectives4 ConclusionsDisclosure of interestContribution to authorshipFundingAcknowledgementsReferences

Documents

2011_06Artacute menorragiahalimeh