Professor and Chair, Department of Obstetrics and Gynecology, Western Michigan University Homer Stryker M.D. School of Medicine, Kalamazoo

Dr. Rebar reports he is the chair of two data safety monitoring boards for Myovant Sciences.

SYNOPSIS: A large, retrospective cohort study using a national claims database revealed that fewer than 20% of young women with heavy menstrual bleeding were screened for von Willebrand disease.

SOURCE: Jacobson AE, Vesely SK, Koch T, et al. Patterns of von Willebrand disease screening in girls and adolescents with heavy menstrual bleeding. Obstet Gynecol 2018;131:1121-1129.

Heavy menstrual bleeding (HMB) occurs commonly in young women. It is well known that bleeding disorders must be considered as one of the underlying causes. A quantitative or qualitative deficiency of von Willebrand factor, von Willebrand disease is the most common bleeding disorder in women, affecting an estimated 1.6 million U.S. individuals.¹ In 2001, the American College of Obstetricians and Gynecologists (ACOG) first recommended that adolescents with menorrhagia be screened for von Willebrand disease.²

Jacobson et al used the Truven Health MarketScan Research Databases to identify women between 10 and 17 years of age with a diagnosis of HMB based on ICD-9 codes to investigate the frequency of screening for von Willebrand disease. The Truven Health MarketScan Research Databases include medical prescription claims of more than 109 million total covered lives in the United States and Medicaid data on 8.6 million patients from 14 states from 2011 to 2013. Based on a prior study of Ohio Medicaid patients,³ the authors hypothesized that the frequency of screening in this population, representative of the entire United States, would be low.

Of the 202,000 young women in the database, 23,888 met the inclusion criteria with a diagnosis of HMB, and 986 (4%) met the study definition for severe HMB (defined as heavy menstrual bleeding plus evidence of iron deficiency anemia, a blood transfusion, or an inpatient stay for bleeding). Of the total, 28% were seen at the first visit by obstetrician-gynecologists and 13% were seen by family practitioners. Fewer than one in 10 (8%) of the total population and fewer than one in five of the women with severe HMB (16%) were screened for von Willebrand disease. The younger women (aged 10-13 years) were screened more often than the older women (aged 14-27 years; 13.9% vs. 6.4%; P < 0.001). Logistic regression analysis indicated that women with severe HMB had a significantly increased likelihood of undergoing screening compared to those without severe HMB (16.2% vs. 7.8%; odds ratio [OR], 1.58; 95% confidence interval [CI], 1.31-1.91). Of additional note is that the logistic regression analysis showed that privately insured patients were significantly more likely to be screened for von Willebrand disease than Medicaid patients (8.8% vs. 6.5%; OR, 1.66; 95% CI, 1.47-1.87). Women seeing family practitioners for the initial visit were less likely to undergo screening compared to those seeing obstetrician-gynecologists (3.2% vs. 6.0%; OR, 0.43; 95% CI, 0.34-0.54), but screening by both groups was low.

COMMENTARY

Perhaps the seminal study calling attention to the high incidence of bleeding disorders among young women was a 1981 series published from the Toronto Hospital for Sick Children reporting that 19% of adolescents with menorrhagia had a bleeding disorder.⁴ Because of the heightened realization of the increased incidence of bleeding disorders in young women with HMB, ACOG first issued a Committee Opinion in 2001 urging practitioners to screen adolescents with menorrhagia for von Willebrand disease.² In a subsequent Committee Opinion, ACOG refined the recommendation to urge testing in young women with HMB and one or more of the following: menses longer than seven days or bleeding through a pad or tampon in two hours, anemia, a family history of a bleeding disorder, and a history of bleeding after a hemostatic challenge (i.e., tooth extraction, surgery, delivery).⁵

Despite such recommendations, the Jacobson et al study documents that screening for von Willebrand disease rarely is performed among young women with HMB. Why is this the case? Certainly, taking an appropriate history is the first step and is accomplished easily by all clinicians. The testing can be complicated, but initial testing for HMB is straightforward. A blood type and crossmatch are warranted for any woman who is hemodynamically unstable on initial presentation. A complete blood count with differential and platelet count and a pregnancy test always are indicated. Initial testing for a bleeding disorder should include prothrombin time, partial thromboplastin time, thrombin time, and fibrinogen level. At this point, referral to a hematologist probably is warranted because no simple, single laboratory test is available to screen for von Willebrand disease. The initial laboratory assessment for von Willebrand disease includes measurement of von Willebrand factor antigen, ristocetin cofactor activity, and factor VIII coagulant activity.⁶ All three tests are recommended for initial evaluation and also may suggest the type and severity of von Willebrand disease.

I chose to highlight this paper because I was so surprised by the findings. From my early days of medical school, it was always emphasized to rule out a bleeding disorder in any individual with unexplained heavy bleeding. That admonition still rings true today, and this paper emphasizes the need for evaluation in women with HMB. Study after study now have reported that approximately 20% of young women with HMB have a bleeding disorder, and von Willebrand disease is the most common. Let us never forget to evaluate young women who present with HMB.

REFERENCES

1. Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand’s disease. Blood 1987;69:454-459.
2. American College of Obstetricians and Gynecologists. Von Willebrand disease in women. ACOG Committee Opinion No. 451. Obstet Gynecol 2009;114:1439-1443.
3. Khamees D, Klima J, O’Brien SH. Population screening for von Willebrand disease in adolescents with heavy menstrual bleeding. J Pediatr 2015;166:195-197.
4. Claessens EA, Cowell CA. Acute adolescent menorrhagia. Am J Obstet Gynecol 1981;139:277-280.
5. American College of Obstetricians and Gynecologists. Von Willebrand disease in women. ACOG Committee Opinion No. 580. Obstet Gynecol 2013;122:1368-1373.
6. Nichols WL. Von Willebrand disease and hemorrhagic abnormalities of platelet and vascular function. In Goldman L, Schafer AI, eds. Goldman-Cecil Medicine. 25th ed. Philadelphia: 2016; 1167-1171.
7. Haamid F, Sass AE, Dietrich JE. Heavy menstrual bleeding in adolescents. J Pediatr Adolesc Gynecol 2017;30:335-340.