Reproductive tract bleeding in women is a naturally occurring event during menstruation and childbirth. In women with menorrhagia, however, congenital bleeding disorders historically have been underdiagnosed.

This consensus is intended to allow physicians to better recognize bleeding disorders as a cause of menorrhagia and consequently offer effective disease-specific therapies.

Key words: coagulation factor, menorrhagia, postpartum hemorrhage, von Willebrand disease, von Willebrand factor

Article Outline

• • Abstract
• • Background
• • What is menorrhagia?
• • When should a gynecologist suspect a  
•    bleeding disorder and pursue a diagnosis?
• • What hematologic evaluations should be ordered and when should they be repeated?
• • How should menorrhagia be managed in women with bleeding disorders?
• • How can PPH be prevented in women with bleeding disorders?
• • Menorrhagia and RBDs: what do we know?
• • Comment
• • Appendix. Selected Terms
• • References
• • Copyright

Bleeding from the reproductive tract in women is a naturally occurring event, generally the result of menstruation and childbirth, and is not associated with a bleeding disorder in most cases.

In those women who do have a bleeding disorder such as von Willebrand disease (VWD), there is an increased incidence of pathologic bleeding.

Menstruation and childbirth may lead thereby to unacceptable blood loss.

The lack of a clinical tool for the objective assessment of abnormal reproductive tract bleeding and the lack of awareness of the potential of bleeding disorders to exacerbate or even cause abnormal bleeding1 leads to the underdiagnosis and suboptimal treatment of women with bleeding disorders.

For Editors' Commentary, see Table of Contents

To highlight the significance of this problem and to provide an expert consensus on how to specifically identify and manage bleeding disorders in obstetrics and gynecology, specialists in the care of women with bleeding disorders met on September 20, 2007, for a consensus conference.

The specialists represented a diverse group of experts in the fields of obstetrics and gynecology and hematology.

The meeting participants were from a variety of institutions in North America, Europe, and New Zealand. CSL Behring (Marburg, Germany) provided financial support to allow the participants to convene.

The meeting was structured as a series of presentations on menorrhagia, bleeding disorders that included VWD, diagnosis and treatment of women with both conditions, management of postpartum hemorrhage (PPH) in women with bleeding disorders, and reproductive tract bleeding in women with rare bleeding disorders (RBDs).

Six central questions were addressed by the meeting's discussion, which are used as section headings herein, and a consensus was sought for each question.

 The consensus is meant to provide clinical information to obstetricians and gynecologists and recommend strategies for the identification and confirmation of a bleeding disorder that could underlie reproductive tract bleeding and offer potential management strategies.

Where no consensus could be reached, no advice is given. VWD is the bleeding disorder of main concern for this consensus. Recommendations have been assigned a grade and level of evidence; the use of the United States Agency for Health Care Policy and Research Criteria is summarized in the Table.2

Levels of evidence2

James. VWD and other bleeding disorders in women. Am J Obstet Gynecol 2009.

Before the meeting, members of the group reviewed pertinent references from their own searches, databases, and publications. In addition, Dr Andra James served on the expert panel that authored the US National Heart Lung and Blood Institute's guidelines, The Diagnosis, Evaluation and Management of von Willebrand Disease.

She reviewed the guidelines in their entirety and reviewed all of the references that pertained to women's health issues and VWD that were compiled for that document.

A description of that literature search, which covered the years 1990-2006, is described elsewhere.3 Dr Augusto Federici coauthored and reviewed the Italian Guidelines for the Diagnosis and Management of von Willebrand Disease.4 Dr Rezan Abdul-Kadir coauthored and reviewed the United Kingdom Haemophilia Doctors' Organization guidelines for the treatment of women with inherited bleeding disorders.5

The prevalence of menorrhagia in women with VWD is 74-92%.6, 7, 8

The prevalence increases according to severity of VWD type, with a higher percentage in VWD type 3 than in types 1 and 2.9

Conversely, the prevalence of VWD in women with menorrhagia is 5-24%, with an overall prevalence of 13% (95% confidence interval [CI], 11-16%) based on a systematic review of 11 studies comprising 988 women with menorrhagia.10

Bleeding disorders, especially VWD with an incidence of approximately 1% in the general population,11, 12, 13 are therefore of notable concern in women with menorrhagia.

VWD is an inherited disease, and although it affects male and female with equal frequency, women are more likely to manifest the disorder clinically because of the bleeding challenges that are associated with menstruation and childbirth.14

Unlike in menorrhagia, there are no studies that document an increased prevalence of bleeding disorders among women with PPH.15, 16

Nonetheless, PPH is an anticipated problem in women with bleeding disorders, particularly delayed or secondary PPH, that occurs > 24 hours after delivery.

There are multiple case reports and case series that document the increased risk of PPH in women with VWD,17, 18, 19, 20, 21, 22, 23, 24, 25 but only 4 case control studies have compared the rate of PPH in women with VWD with the rate in women without PPH7, 26, 27, 28; there is only 1 study in which ascertainment was not retrospective.26

That study did show a statistically significant difference between the rate of PPH in women with VWD (6%) and the rate in women without VWD (4%).

Unlike PPH in the general population, which occurs overwhelmingly in the immediate postpartum period,29, 30 in women with VWD, PPH may be delayed.23, 25

In a review of published cases,31 the average day of examination was 15 days after delivery.

VWD is caused by a deficiency in, or a dysfunction of, von Willebrand factor (VWF). VWF is a multimeric protein synthesized in megakaryocytes and endothelial cells.

It has 2 main hemostatic functions. In primary hemostasis at the site of injured vessel walls, it facilitates platelet adhesion to subendothelial structures (such as exposed collagen fibers) and supports platelet aggregation and thrombus formation.

As part of secondary hemostasis, VWF acts as a carrier protein for coagulation factor VIII (FVIII), stabilizing and protecting FVIII procoagulant activity. Type 1 VWD results from a deficiency of VWF. Type 2 VWD results from abnormal VWF. There are 4 subtypes: type 2A is characterized by a deficiency of normal multimers of VWF; type 2B is characterized by VWF with enhanced platelet binding and can result in thrombocytopenia; type 2M is characterized by VWF with reduced platelet binding; and type 2N is characterized by VWF with reduced binding to FVIII, which allows FVIII to be proteolyzed.

Type 3 VWD results from the absence or near absence of VWF. With the exception of type 3, which is rare and severe; cases of type 2N VWD is generally inherited by autosomal dominant transmission.3

Individuals with VWD are at an increased risk for mucocutaneous bleeding that includes epistaxis, easy bruising, prolonged bleeding after trivial cuts, excessive bleeding with dental procedures, excessive bleeding from the oral cavity, gastrointestinal bleeding, excessive postoperative bleeding, and reproductive tract bleeding.32, 33

The signs and symptoms of VWD depend on the type and severity of the disease.

Most people with type 1 disease have bleeding that is mild-to-moderate in severity, does not require routine transfusions or other treatments, and is not life-threatening.

Life-threatening bleeding that involves the brain or gastrointestinal tract can occur in individuals with type 3 disease, in some individuals with type 2 disease, and, rarely, in individuals with type 1 disease.

Bleeding within deep tissues, such as muscles and joints, may occur in individuals with type 3 disease.3 The most common symptom that women with VWD experience is menorrhagia.3

SEE FULLTEXT

American Journal  Obtetrics & Gynecology