Bleeding Disorders May Cause Menorrhagia and Postpartum Hemorrhage

A consensus meeting aimed to improve recognition of bleeding disorders as a cause of menorrhagia and postpartum hemorrhage so that effective disease-specific treatment can be provided.
"In those women who do have a bleeding disorder such as von Willebrand disease (VWD), there is an increased incidence of pathologic bleeding....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 bleeding leads to the underdiagnosis and suboptimal treatment of women with bleeding disorders."
Although menorrhagia or postpartum hemorrhage may result in considerable, clinically significant blood loss, congenital bleeding disorders exacerbating these conditions historically tend to be underdiagnosed, presumably because of lower awareness among obstetricians and gynecologists vs hematologists.
Clues suggesting the possibility of an underlying bleeding disorder include a family or personal history of bleeding events. Recognizing these clues should improve collaboration among obstetrician-gynecologists and hematologists, reduce diagnosis of "idiopathic" menorrhagia, and result in better management of reproductive tract bleeding events. Women who have these conditions should thereby have improved quality of life and school and work performance indicators.

Questions and Answers Addressed
1. What is menorrhagia?
Although menorrhagia is typically defined as more than 80 mL of blood loss per menstrual cycle, other indicative features are soaking through a pad or tampon within 1 hour, soaking through bed clothes, below normal ferritin levels, anemia, and pictorial blood assessment chart score of more than 100.
2. When should a gynecologist or obstetrician suspect a bleeding disorder and pursue a diagnosis?
Indicators suggesting an underlying bleeding disorder include menorrhagia since menarche, a family history of a bleeding disorder, or failed response to conventional management of menorrhagia.
Other indicators are a personal history of 1 or more of the following: epistaxis; notable bruising without injury; minor wound bleeding; bleeding of oral cavity or gastrointestinal tract without an obvious anatomic lesion; prolonged or excessive bleeding after dental extraction; unexpected postsurgical bleeding; hemorrhage from ovarian cysts or corpus luteum; hemorrhage requiring blood transfusion; and PPH, especially delayed PPH.
Even in the presence of gynecologic disease such as uterine fibroids, a bleeding disorder may contribute to menorrhagia.
3. What hematologic evaluations should be ordered, and when should they be repeated?
Platelet number and function and specific coagulation factor profile should be evaluated in consultation with a hematologist. Other tests should include complete blood cell count, activated partial thromboplastin time, prothrombin time, VW factor (VWF) measured with ristocetin cofactor activity and antigen, coagulation factor VIII, and fibrinogen.
If results of these tests are normal, women should undergo testing of platelet aggregation and platelet release. Although testing should not be delayed to coincide with menstruation, subsequent testing during menses should be considered if the first set of VWF levels is at the lower limit of normal.
Hormonal contraception should not be interrupted to permit testing.
4. How should menorrhagia be managed in women with bleeding disorders?
Tranexamic acid (1 - 1.5 g, 3 - 4 times/day) may be given before hematologic testing, although management is optimally started once the diagnosis is made. Nonsteroidal anti-inflammatory drugs should be avoided. Further management strategies differ based on whether future fertility and/or becoming pregnant soon are desired. A combination of therapies is often needed, and consultation with a hematologist is essential. Hemostatic treatment should start on the first or second day of menses.
5. How can PPH be prevented in women with bleeding disorders?
Hematology consultation and collaborative care are recommended. VWF levels should be determined. If the coagulation factor profile is not in the normal range by the third trimester, delivery should take place at a specialized center. If third-trimester VWF levels are 50 IU/dL or more, epidural analgesia/anesthesia may be considered safe for delivery; otherwise, appropriate hemostatic cover is required. Adequate venous access is needed during labor, and the third stage of labor should be actively managed.
6. What do we know about menorrhagia and RBDs?
Tranexamic acid and aminocaproic acid or desmopressin (DDAVP) is useful for the treatment of menorrhagia in combined factor V or factor VIII deficiency, but additional research is needed to determine its role in other RBDs. Patients should be treated with antifibrinolytic treatment and appropriate factor replacement when available.
"An awareness of bleeding disorders (such as VWD, RBDs, and platelet disorders) is an important asset for obstetricians and gynecologists," the consensus authors write. "These disorders remain underdiagnosed in women with menorrhagia and potentially in other cases of abnormal bleeding (such as PPH)....The authors of this consensus believe that these recommendations will aid obstetricians and gynecologists to better anticipate, prepare for, and manage cases of abnormal reproductive tract bleeding in women with bleeding disorders."

Clinical Context
RBDs are inherited autosomally, with prevalence ranging from 1 in 2 million for factor II and factor XIII deficiencies to 1 in 500,000 for factor XI and factor VII deficiencies. The number affected by RBDs around the world has reached approximately 7000, with the most common being factor XI deficiency. VWD affects menstruation and childbirth and may lead to unacceptable blood loss. Because of menses and childbirth, VWD is more likely to present in women vs men, although the prevalence is similar between the sexes.
This is a consensus panel review constructed by obstetricians and gynecologists with hematologists based on a 2007 meeting of the literature on VWD in women focusing on presentation, diagnosis, and treatment strategies.

Clinical Implications
• The prevalence of VWD in adult women with menorrhagia is 13%, increasing to 33% in adolescents, and diagnosis is made by assessing risk factors and performing hematologic evaluation.
• In women with VWD who desire fertility, medical management is recommended, and VWF level should be at least 50 IU/dL to prevent PPH.