Heavy Menstrual Bleeding and Underlying Bleeding Disorders: Should All Women Be Tested?

Abstract & Commentary

By Rebecca H. Allen, MD, MPH

Assistant Professor, Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI

Dr. Allen reports no financial relationships relevant to this field of study.

Synopsis: In this sample of 102 consecutive Dutch patients with heavy menstrual bleeding, the overall prevalence of an underlying bleeding disorder was 29%, with the most common being disorders of platelet function. There was no difference in the prevalence of a bleeding disorder among women with and without a gynecologic explanation for their bleeding (fibroids or polyps).

Source: Knol HM, et al. The prevalence of underlying bleeding disorders in patients with heavy menstrual bleeding with and without gynecologic abnormalities. Am J Obstet Gynecol 2013;209:202.e1-7.

This prospective study enrolled 102 consecutive patients presenting to the gynecology clinic at the University Medical Centre of Groningen in the Netherlands between March 2007 and December 2010 who had a history of heavy menstrual bleeding. The investigators used the Pictorial Bleeding Assessment Chart (PBAC) to assess the amount of bleeding and patients with a score of < 100 were excluded as well as any women with known bleeding disorders, IUD use in the past 2 months, and treatment with anticoagulants, antifibrinolytics, NSAIDs, combined oral contraceptives, or progestins. Women then underwent a workup including a transvaginal ultrasound and sonohysterogram if indicated. Women with documented fibroids > 2 cm, uterine polyps, endometrial hyperplasia, or endometritis were classified as heavy menstrual bleeding explained by gynecologic abnormalities; all others were classified as unexplained. Women were then tested for bleeding disorders, including von Willebrand disease, coagulation factor deficiencies, and platelet defects, in the early follicular phase of their cycle. No sample size calculation was reported.

The median age of the sample was 42.5 years (range, 17-55 years) and 95% were white. Seventy-four percent of the women had unexplained and 26% had explained heavy menstrual bleeding (9% uterine polyps and 17% submucosal fibroids). Overall, 31% of the patients in the unexplained group had a bleeding disorder compared to 27% in the group with gynecologic abnormalities (P = 0.48). The distribution of bleeding disorder types was no different between the two groups. Among those with a bleeding disorder, the most common diagnosis (76%) was a platelet defect followed by von Willebrand disease (20%), low factor XI (13%), combination disorder (13%), and factor VII deficiency (3%). The investigators also compared the study sample to a group of 28 healthy volunteers who did not have subjective heavy menstrual bleeding. Their rationale was to compare the levels of coagulation factors in the subjects to controls, in addition to standard normal lab ranges. However, the inclusion criteria were different for these women, so they don’t appear to be an appropriate control group. Nevertheless, the remainder of the study yields interesting information.

COMMENTARY

This is yet another study reminding us that bleeding disorders are not uncommon among women with heavy menstrual bleeding. According to the authors, the novel finding in this study was the presence of bleeding disorders among women who may have a gynecological explanation for their heavy menstrual bleeding as well. However, in this study, the authors did not prove or disprove which abnormality was the actual cause of the heavy menstrual bleeding. In addition, endometrial polyps are not a common cause of regular heavy menstrual bleeding. Despite this, the study tells us that if treatment of the gynecologic cause of bleeding is unsuccessful, then perhaps an assessment for bleeding disorders is indicated. The overall diagnosis of von Willebrand disease among women with heavy menstrual bleeding was on the lower end in this study (6%) than previously reported in other studies (5-20%). The authors speculated that this was due to the study population being ethnically homogeneous.

Abnormal uterine bleeding (AUB) is now classified according to the PALM-COEIN system. PALM stands for the structural causes: Polyp, Adenomyosis, Leiomyoma, and Malignancy and hyperplasia. COEIN refers to the non-structural causes: Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, and Not yet classified. AUB is paired with descriptive terms such as heavy menstrual bleeding and intermenstrual bleeding. It is then further classified by one (or more) letter qualifiers that indicate the etiology or etiologies. The American College of Obstetricians and Gynecologists recommends that all women with heavy menstrual bleeding be screened for the possibility of bleeding disorders.¹ For a positive screen, women must report heavy menstrual bleeding since menarche or one of the following: postpartum hemorrhage, surgery-related bleeding, bleeding associated with dental work, or two or more of the following symptoms: bruising one to two times per month, epistaxis one to two times per month, frequent gum bleeding, or family history of bleeding symptoms. For those who screen positive, initial tests include a complete blood count, prothrombin time, and partial thromboplastin time. The diagnosis of von Willebrand disease can be complex and referral to a hematologist is advisable if a bleeding disorder is suspected.² Although we commonly think of diagnosing bleeding disorders in adolescence, many women are not diagnosed until adulthood, as this study shows.

The first-line treatment for menorrhagia in women with bleeding disorders, including von Willebrand disease, is typically oral contraceptive pills.³ Combined oral contraception increases coagulation factors as well as induces endometrial atrophy. Another appealing option includes the levonorgestrel intrauterine system (LNG-IUS), especially in women with contraindications to estrogen. One study evaluated LNG-IUS use in 16 women with inherited bleeding disorders and menorrhagia.⁴ Nine women became amenorrheic; in the remaining 7 women, PBAC scores decreased significantly from a median of 213 to 47. Quality of life was improved and long-term effectiveness has been documented up to a median duration of 53 months. Other options for women who desire pregnancy or have failed hormonal options include DDAVP, antifibrinolytics such as transexemic acid, and von Willebrand factor concentrates.² It seems that it would behoove obstetrician-gynecologists to develop a relationship with a hematologist in their area to assist in comanaging these women.

References

1. ACOG Practice Bulletin No. 128. Diagnosis of Abnormal Uterine Bleeding in Reproductive-Aged Women. July 2012.
2. James AH, et al. Von Willebrand disease: Key points from the 2008 National Heart, Lung, and Blood Institute guidelines. Obstet Gynecol 2009;114:674-678.
3. ACOG Committee Opinion No. 451. Von Willebrand Disease in Women. Obstet Gynecol 2009;114:1439-1443.
4. Kadir RA, Chi C. Levonorgestrel intrauterine system: Bleeding disorders and anticoagulant therapy. Contraception 2007;75(6 Suppl):S123-S129.