22 Chapter 2 After identifying relevant titles and abstracts of the selected studies, two independent authors (HPE, MCP) made a final selection of eligible articles after full-text assessment of the remaining relevant studies. Reference lists of relevant articles were cross-checked for additional relevant studies. Duplicates were removed manually. Any disagreements were resolved by discussion and, if necessary, by consulting a third reviewer (JCL). Data collection and risk of bias assessment Data was independently extracted from the selected articles by two reviewers (HPE, MCP) using a standardized format including items about the general study characteristics (design, setting, VWD population), type of VWD, type of surgical treatment and the outcomes. We accepted any definition or description of bleeding complication that was used by the primary study related to blood loss which required re-intervention, re-treatment or blood transfusion. Second generation EA included bipolar endometrium ablation, balloon endometrium ablation, microwave ablation, thermal ablation or endomyometrial ablation. Hysterectomy included any laparoscopic, vaginal or laparotomic type of hysterectomy. VWD classification was based on terminology provided in the selected studies. Studies with unclear reporting of VWD as a type of bleeding disorder were excluded. Study design was defined as cohort study when the patients were included into the study during a certain period of time, and a case study was defined if patient selection was not described. (12) Outcomes were classified as counts and percentages in cohort studies if available or possible to extract. Study quality was assessed by two independent authors (HPE, MCP) with the Methodological Index for Non-Randomized Studies (MINORS) (13) instrument. The items are scored 0 (not reported), 1 (reported but inadequate), 2 (reported but adequate), NA (Not Applicable). The global ideal score is 16 for noncomparative studies. Any disagreements were resolved by consulting a third author (JCL). RESULTS Our search resulted in 1102 records, of which 1090 records were excluded with the following reasons, no bleeding disorder (N=532), no EA or hysterectomy (N=221), oncology (N=81). Eligible for inclusion were 256 records (Figure 1: Prisma flow chart for identifying eligible studies on prophylactic and therapeutic strategies for intraoperative bleeding in von Willebrand disease women undergoing EA or hysterectomy for heavy menstrual bleeding). After assessment of the abstracts, 244 studies were excluded with following reasons, review (N=24), study protocol (N=1), non VWD patients (N=161), no EA or hysterectomy (N=42), no pre-described outcome (complication/pre-treatment) (N=16). The final selection consisted of one case report (14) and eleven retrospective studies (3, 14-24) describing a total of 691 VWD women. The exact number per type VWD was unclear due to incomplete reporting in four studies. (14, 15, 17, 21) Data on study characteristics, adverse events and bleeding complications in EA or hysterectomy are summarized in Table 1. (3, 14-24)
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