27 Systematic review Risk of bias A summary of the quality assessment for all included studies is provided in Table 2. The quality of the included studies was rated as ‘low’ (median MINORS score 11 out of 16). The certainty in the evidence was ‘low’ for all outcomes due to the observational designs of all studies (11 retrospective studies and one case report). Prophylactic and therapeutic strategies In the individual patient data, information on adequate prophylactic and therapeutic strategies in both EA and hysterectomies could be extracted for 54 procedures. Prophylaxis consisted mostly of tranexamic acid (type 1 or type 3), (17, 20) desmopressin (type 1), (16, 17) VWF/FVIII concentrate (type 1, type 2A, type 2N, or acquired). (22, 16) Levels of hemoglobine of VWF before surgery were not mentioned in any of the included articles. Information about specific sugical management procedures like the use of bipolar electrosurgical intruments, intended for effectively seals of vessels to reduce intraoperative bleeding during hysterectomies, were not mentioned. The described surgical procedures in included VWD women (type 1, type 2A, type 2N, type 3 and acquired) were (sub)total abdominal hysterectomy, vaginal hysterectomy, laparoscopic hysterectomy (LH) or (robotic) laparoscopic assisted vaginal hysterectomy (LAVH) in 7 studies (N=661; one case report (14) and 6 retrospective studies). (3, 20-24) and bipolar EA techniques in 7 studies (N=30; all retrospective studies). (15-20, 22) Bleeding complications in relation to surgical procedures (hysterectomy, EA) The International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (ISTH-BAT) was used for screening underlying bleeding disorders in one EA study. (17) No other included studies reported on validated screening tools to determine the patients’ bleeding tendency before surgery. Individual information on the VWD diagnosis was described before surgery in 16% (108/691) (3, 15-20, 22, 23) of the included procedures, while in 5% (38/691) (3), (14), (24) of the procedures a VWD diagnosis was made after surgery, and in 79% (545/691) (21) of cases, the timing of the VWD diagnosis was not described. Eleven out of twelve studies evaluated bleeding complications by using medical records. (14-24) One study evaluated bleeding complications by self-reporting feedback. (3) In the individual patient data, information on intra- or postoperative bleeding complications during hysterectomy in VWD women was available in 7% (49/661) procedures. Namely, this was reported in 4 retrospective studies as being 3% (15/545) (21), 29% (2/7) (24), 58% (29/50) (3), 60% (3/5) (23) and a case-report described one vaginal vault bleeding. (14) One cohort study reported 7% (40/545) transfusion rate in VWD women compared to 2% (28509/1357588) in the control group. (21) Two cohort studies did not report any intra- or postoperative bleeding during hysterectomy. (20, 22) In none of the 7 EA cohort studies, intra- or postoperative bleeding events occurred in VWD women (0%, 0/30). (15-20, 22) 2
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