Iron Deficiency Anemia and Von Willebrand Disease in Women with Menorrhagia

Introduction

Von Willebrand disease (VWD) is the most common bleeding disorder in adolescents and adult women that causes heavy menstrual bleeding (HMB) (Blood Adv 2020;13:3209-3216). HMB is defined as bleeding lasting >7 days or > 80 mL of blood per menstrual cycle; a broader definition includes an excessive blood loss that interferes with a woman´s physical, emotional, social and material quality of life; an underlying bleeding disorder should be considered if IDA is present (Am J Obstet Gynecol 2009;201:12.e1-12.e8 and Blood 2018;132:2134-2142).

Objective

Identify VWD causing HBM in patients with IDA.

Materials and Methods

Retrospective databased study from 2017 to 2021 of 292 women with IDA due HMB referred to our Institution. HMB was not related to systemic disease, hormonal disorders, renal or hepatic disease. The IDA studies included CBC, iron panel with ferritin levels; diagnosis was based in Clinical Guidelines: Hb< 12 gr/L, transferrin saturation (TS) <20% and ferritin <15 mcg/L (Adv Ther 2021;38:201-225); in all cases sonography was performed to rule out ovarian cyst and fibroma. For VWD, personal and familiar history of bleeding were assessed, studies included bleeding time, fibrinogen, factor VIII, factor XIII, vW antigen and vW activity on first to fourth day of menstruation, all studies were performed twice in different menstrual cycle; diagnosis was based in review articles: vW below 50 IU and bleeding history, including IDA (Hematol Oncol Clin N Am 2021;35:1085-1101).

Results

From 292 women with IDA, 23 (7.9%) was diagnosed with VWD. Age ranges from 14 to 54 years, median 21. vW antigen levels from 3 to 47 IU, median 28 IU. vW activity 4 to 45 IU, median 27 IU. Eleven patients had vW activity levels below 30 IU and had more significant history of mucocutaneous bleeding: epistaxis 52%, cutaneous bleeding 45%, oral cavity bleeding 42%; compared with 12 patients with vW activity between 31 and 50 IU: epistaxis 35%, cutaneous bleeding 19%, oral cavity bleeding 15%. Both groups had similar frequency of bleeding after surgical and dental procedure, 46% and 44% respectively. Treatment for IDA included oral and IV iron; treatment for HMB included hormonal therapy, desmopressin and tranexamic acid.

Discussion

VWD has been objectively reported in México in the first systematic analysis (Haemophila 2013;19:231-235); this observation was made mainly in mestizos of Spanish heritage and the true frequency could not be determinate, as is in the case in the majority of studies in countries worldwide; from 133 patients with bleeding disorders, 53 (39.8%) had VWD. In 124 Mexican women with history of postpartum hemorrhage, VWD was diagnosed in 61 (49.2%) (Haemophilia 2020;26:97-105). In a more recently study, VWD rate was estimated in 7.2 per million inhabitants in western Mexico (Haemophilia 2022;21:e78-e87). Our study demonstrates that VWD is present in Mexican population and has almost a rate of 8% in women with HMB, similar to reported in other studies, but this rate may be underrepresented and underdiagnosed as is in general population because lack of hematologists and diagnostic test in smaller cities, and misconception of the disease, as Mexico has heritage from Spain, England and France among other European countries with higher rates of VWD. Our study also compares the levels of VW factors, and found that patients with low levels of VW (31-50 IU) has the same bleeding phenotype as patients with VWD (< 30 IU), supporting that VWD should be diagnosed in patients with bleeding manifestations and VW factor below 50 IU (Hematol Oncol Clin N Am 2021;35:1085-1101). Finally, based in our results we recommend to investigate for VWD in patients with IDA from HMB.

No relevant conflicts of interest to declare.