Planning Pregnancy and Birth in Women with Inherited Bleeding Disorders.

Inherited bleeding disorders are characterized by a diverse clinical phenotype within and across specific diagnoses. von Willebrand disease (VWD), hemophilia A, and hemophilia B comprise 95 to 97% of inherited bleeding disorders, with the remaining 3 to 5% attributed to rare bleeding disorders, including congenital fibrinogen disorders, factor deficiencies (affecting FII, FV, FV + FVIII, FVII, FX, FXI, and FXIII), and platelet function defects. The pregnancy, birth, and the puerperium may be adversely influenced in the setting of an inherited bleeding disorder depending on its type and clinical phenotype. Obstetric hemostatic challenges may sometimes also unmask the presence of a previously unknown inherited bleeding disorder. This review aims to address the approach to pregnancy and birth in the context of an inherited bleeding disorder and highlights the significance of multidisciplinary input into the care of these women.

Outcomes of long-term von Willebrand factor prophylaxis use in von Willebrand disease: A systematic literature review.

BACKGROUND: Von Willebrand Disease (VWD) is a common inherited bleeding disorder. Patients with VWD suffering from severe bleeding may benefit from the use of secondary long-term prophylaxis. AIM: Systematically summarize the evidence on the clinical outcomes of secondary long-term prophylaxis in patients with VWD and severe recurrent bleedings. METHODS: We searched Medline and EMBASE through October 2019 for relevant randomized clinical trials (RCTs) and comparative observational studies (OS) assessing the effects of secondary long-term prophylaxis in patients with VWD. We used Cochrane Risk of Bias (RoB) tool and the RoB for Non-Randomized Studies of interventions (ROBINS-I) tool to assess the quality of the included studies. We conducted random-effects meta-analyses and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: We included 12 studies. Evidence from one placebo controlled RCT suggested that VWD prophylaxis as compared to no prophylaxis reduced the rate of bleeding episodes (Rate ratio [RR], .24; 95% confidence interval [CI], .17-.35; low certainty evidence), and of epistaxis (RR, .38; 95%CI, .21-.67; moderate certainty evidence), and may increase serious adverse events RR 2.73 (95%CI .12-59.57; low certainty). Evidence from four before-and-after studies in which researchers reported comparative data suggested that VWD prophylaxis reduced the rate of bleeding (RR .34; 95%CI, .25-.46; very low certainty evidence). CONCLUSION: VWD prophylaxis treatment seems to reduce the risk of spontaneous bleeding, epistaxis, and hospitalizations. More RCTs should be conducted to increase the certainty in these benefits.

European principles of care for women and girls with inherited bleeding disorders.

INTRODUCTION: Despite increasing awareness of issues faced by women and girls with inherited BDs (WGBD), standards of care are lacking, with disparities in diagnosis and treatment for WGBD across Europe. We aimed to develop practical principles of care (PoC) to promote standardization of care for WGBD within European Haemophilia Treatment and Comprehensive Care Centres (HTC/CCCs). METHODS: The co-creation process, supported by the European Association for Haemophilia and Allied Disorders, consisted of four multidisciplinary meetings with health care providers (HCPs) experienced in WGBD care, and European Haemophilia Consortium representatives, combined with broad patient and HCP consultations in the European haemophilia community. Relevant medical societies outside Europe were contacted for confirmation. RESULTS: We developed ten PoC for WGBD, stressing the importance and benefits of a centralized, multidisciplinary, comprehensive, family-centred approach to support and manage WGBD during all life stages. These PoC emphasise the right to equitable access and quality of care for all people with BDs, irrespective of gender. Multiple medical societies outside Europe also confirmed their support for endorsement. CONCLUSIONS: Ten PoC for WGBD evolved from an iterative process among stakeholders, supported by relevant medical societies worldwide. These PoC can serve as a benchmark for diagnosis and comprehensive multidisciplinary management of WGBD, and improve awareness of their unique challenges. They offer a framework to guide HTC/CCCs in providing equitable care for all WGBD, both in their own services and in other healthcare settings. Implementation of these principles aims to positively impact the health, wellbeing and quality of life for WGBD.

Antithrombotic prophylaxis for surgery-associated venous thromboembolism risk in patients with inherited platelet disorders. The SPATA-DVT Study.

Major surgery is associated with an increased risk of venous thromboembolism (VTE), thus the application of mechanical or pharmacologic prophylaxis is recommended. The incidence of VTE in patients with inherited platelet disorders (IPD) undergoing surgical procedures is unknown and no information on the current use and safety of thromboprophylaxis, particularly of low-molecular-weight-heparin in these patients is available. Here we explored the approach to thromboprophylaxis and thrombotic outcomes in IPD patients undergoing surgery at VTE-risk participating in the multicenter SPATA study. We evaluated 210 surgical procedures carried out in 155 patients with well-defined forms of IPD (VTE-risk: 31% high, 28.6% intermediate, 25.2% low, 15.2% very low). The use of thromboprophylaxis was low (23.3% of procedures), with higher prevalence in orthopedic and gynecological surgeries, and was related to VTE-risk. The most frequently employed thromboprophylaxis was mechanical and appeared to be effective, as no patients developed thrombosis, including patients belonging to the highest VTE-risk classes. Low-molecular-weight-heparin use was low (10.5%) and it did not influence the incidence of post-surgical bleeding or of antihemorrhagic prohemostatic interventions use. Two thromboembolic events were registered, both occurring after high VTE-risk procedures in patients who did not receive thromboprophylaxis (4.7%). Our findings suggest that VTE incidence is low in patients with IPD undergoing surgery at VTE-risk and that it is predicted by the Caprini score. Mechanical thromboprophylaxis may be of benefit in patients with IPD undergoing invasive procedures at VTE-risk and low-molecular-weight-heparin should be considered for major surgery.

Heavy menstrual bleeding in women with inherited bleeding disorders.

Heavy menstrual bleeding (HMB) is the commonest bleeding symptom among women with inherited bleeding disorders (IBD). Since HMB starts at the very onset of menarche and continues throughout the reproductive life, the health related quality of life of these women is affected and they are at an increased risk of developing iron-deficiency anemia. Because of the entrenched stigma and taboos, women and girls are often reluctant to discuss the problem of HMB within their families and do not seek medical advice. Increased awareness and multidisciplinary management approach for the management of these women are essential in ensuring an optimal outcome. It is important to take a careful history and undertake a thorough gynecological assessment to exclude other underlying/concomitant causes of HMB. Iron supplementation is essential. Strategies for decreasing menstrual blood flow are similar to those used for HMB in general with the addition of desmopressin and replacement therapy and the exclusion of non-steroidal anti-inflammatory drugs. Tranexamic acid and/or hormonal intervention are usually recommended as first-line therapy. Treatment choice should be individualized taking into account whether the woman wishes to preserve her fertility, if she requires contraception, the type of IBD, the severity of bleeding, and her social and religious background as well as acceptability and availability of the treatment options.

Clinical management of woman with bleeding disorders: A survey among European haemophilia treatment centres.

INTRODUCTION: The impact of bleeding for women with bleeding disorders (WBD) is of increasing focus and importance. Despite this, optimal management strategies are unclear and knowledge gaps persist. AIM: To examine practices and define research priorities on diagnosis and management of WBD in Europe. METHODS: An electronic survey on clinical management of WBD was sent to 136 European haemophilia treatment centres (HTCs), including open questions on knowledge gaps and research priorities. RESULTS: Fifty-nine HTCs from 12 Western (WE) and 13 Central/Eastern European (CEE) countries completed the survey. Less than half runs a joint clinic (24 HTCs, 42%). Most centres without a joint clinic have a named obstetrician (81%) and/or gynaecologist (75%) available for collaboration. Overall 18/54 (33%) European HTCs do not offer preimplantation genetic diagnosis. Third trimester amniocentesis to guide obstetric management is available 28/54 HTCs (52%), less frequent in CEE compared to WE countries (5/17 vs 23/37, P = .03). 53% of HTCs (28/53) reported that only 0%-25% of WBD seek medical advice for heavy menstrual bleeding (HMB). An algorithm managing acute HMB in WBD is lacking in 22/53 (42%) HTCs. The main reported knowledge and research gaps are lack of awareness & education on WBD among patients and caregivers, optimal diagnostic strategies and effective multidisciplinary management of pregnancy & HMB. CONCLUSION: Joint clinics, prenatal diagnostics and algorithms for managing acute HMB are lacking in many European HTCs. HMB may be an underestimated issue. This survey highlights the need to prioritize improvement of knowledge and patient care for WBD across Europe.

European guidelines on perioperative venous thromboembolism prophylaxis: Surgery during pregnancy and the immediate postpartum period.

: Thromboembolic events in the pregnant and postpartum patient remain rare but potentially fatal complications. The aim of this section was to analyse the few prospective studies addressing the issue of thromboprophylaxis following a surgical procedure during and immediately after pregnancy, as well as national guidelines, and to propose European guidelines on this specific condition. Thromboprophylaxis is broadly recommended due to the combined risks of surgery and pregnancy or the postpartum period, regardless of the mode of delivery. We recommend prophylactic thromboprophylaxis following surgery during pregnancy or the postpartum period when they imply, as a consequence, bed rest, until full mobility is recovered (Grade 1C). Similarly, thromboprophylaxis should be used in cases of perioperative infection during pregnancy or the postpartum period. Concerning thromboprophylaxis following a caesarean section, it seems avoidable only in elective procedures in low-risk patients, after a normal pregnancy, and with an early rehabilitation protocol. The duration of thromboprophylaxis following caesarean section should be at least 6 weeks for high-risk patients, and at least 7 days for the other patients requiring anticoagulation (Grade 1C).

Evaluation and management of postpartum hemorrhage: consensus from an international expert panel.

BACKGROUND: Postpartum hemorrhage (PPH) remains one of the leading causes of maternal morbidity and mortality worldwide, although the lack of a precise definition precludes accurate data of the absolute prevalence of PPH. STUDY DESIGN AND METHODS: An international expert panel in obstetrics, gynecology, hematology, transfusion, and anesthesiology undertook a comprehensive review of the literature. At a meeting in November 2011, the panel agreed on a definition of severe PPH that would identify those women who were at a high risk of adverse clinical outcomes. RESULTS: The panel agreed on the following definition for severe persistent (ongoing) PPH: "Active bleeding >1000 mL within the 24 hours following birth that continues despite the use of initial measures including first-line uterotonic agents and uterine massage." A treatment algorithm for severe persistent PPH was subsequently developed. Initial evaluations include measurement of blood loss and clinical assessments of PPH severity. Coagulation screens should be performed as soon as persistent (ongoing) PPH is diagnosed, to guide subsequent therapy. If initial measures fail to stop bleeding and uterine atony persists, second- and third-line (if required) interventions should be instated. These include mechanical or surgical maneuvers, i.e., intrauterine balloon tamponade or hemostatic brace sutures with hysterectomy as the final surgical option for uncontrollable PPH. Pharmacologic options include hemostatic agents (tranexamic acid), with timely transfusion of blood and plasma products playing an important role in persistent and severe PPH. CONCLUSION: Early, aggressive, and coordinated intervention by health care professionals is critical in minimizing blood loss to ensure optimal clinical outcomes in management of women with severe, persistent PPH.

Report of the ISTH registry on pregnancy and COVID-19-associated coagulopathy (COV-PREG-COAG).

Background: Concerns about COVID-19-associated coagulopathy (CAC) in pregnant individuals were raised in early pandemic. Methods: An ISTH-sponsored COVID-19 coagulopathy in pregnancy (COV-PREG-COAG) international registry was developed to describe incidence of coagulopathy, VTE, and anticoagulation in this group. Results: All pregnant patients with COVID-19 from participating centers were entered, providing 430 pregnancies for the first pandemic wave. Isolated abnormal coagulation parameters were seen in 20%; more often with moderate/severe disease than asymptomatic/mild disease (49% vs 15%; p < 0.0001). No one met the ISTH criteria for disseminated intravascular coagulopathy (DIC), though 5/21 (24%) met the pregnancy DIC score. There was no difference in antepartum hemorrhage (APH) with asymptomatic/mild disease versus moderate/severe disease (3.4% vs 7.7%; p = 0.135). More individuals with moderate/severe disease experienced postpartum hemorrhage (PPH) (22.4% vs 9.3%; p = 0.006). There were no arterial thrombotic events. Only one COVID-associated venous thromboembolism (VTE) was reported. Conclusions: Low rates of coagulopathy, bleeding, and thrombosis were observed among pregnant people in the first pandemic wave.

Hematologic characteristics and coagulopathy in pregnancy with COVID-19 succeeding the first wave: a multicenter retrospective cross-sectional study.

Background: Early reports have demonstrated an association of COVID-19 infection during pregnancy and postpartum period with coagulopathy and bleeding complications and indicated that pregnant people with COVID-19 are more likely to experience coagulopathy and venous thromboembolism. A recent report concerning such complications during the first wave of the pandemic was reassuring; however, no publications have evaluated these issues in the context of increased illness severity with the emergence of SARS-CoV-2 variants of concern. Objectives: We performed a retrospective, multinational cohort study in Canada, Romania, and the United Kingdom, aiming to provide a comprehensive analysis of the hematologic test characteristics of pregnancies affected by COVID-19 after the first wave of the pandemic. Results: Three-hundred-seventy patients were evaluated. Markers of inflammation and endothelial dysfunction were significantly elevated, in keeping with observations in the nonpregnant population. Reassuringly, despite more severe disease noted in succeeding waves of the pandemic, there was no significant evidence of COVID-19-associated coagulopathy, and overall, no association was demonstrated between isolated coagulation abnormalities and bleeding risk. Notably, fibrinogen below 2g/L was again linked with the risk of postpartum hemorrhage. Finally, venous thromboembolism risk was low but noted more frequently in those with severe illness despite thromboprophylaxis. Conclusion: Our findings add valuable insights into the nature of hematologic test characteristics, bleeding, and thrombotic complications for those affected with COVID-19 in pregnancy, reassuring readers of the low incidence of bleeding and thrombotic complications but inviting further debate as to the degree of thromboprophylaxis that may benefit the subgroup with severe disease.

Management of pregnancy and delivery in congenital fibrinogen disorders: communication from the ISTH SSC Subcommittee on Factor XIII and Fibrinogen.

Congenital fibrinogen disorders (CFDs) are a heterogeneous group of rare congenital quantitative and/or qualitative fibrinogen deficiencies. The spectrum of molecular anomalies is broad, leading to several subtypes of fibrinogen disorders (ie, afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia). Pregnancy in women with CFDs is a high-risk clinical situation, with an increased tendency for miscarriages, bleeding, and thrombosis. Even though it is well established that management of such pregnancies requires a multidisciplinary approach involving specialists (hematologists and maternal/fetal medicine experts with expertise in the management of inherited bleeding disorders), specific guidelines are lacking. In this International Society on Thrombosis and Haemostasis (ISTH) Scientific and Standardization Committee communication, we aim to propose an expert consensus opinion with literature evidence where available on the strategy for management of pregnancy, delivery, and puerperium in CFDs.

Postmortem diagnosis of severe factor X deficiency in a fetus with intracranial hemorrhage resulting in intrauterine death.

In patients with severe congenital factor X deficiency, spontaneous intracranial hemorrhage (ICH) is particularly frequent in early childhood. We describe a case of fetal death at 26 weeks due to massive ICH. Gene panel analysis of postmortem samples revealed homozygosity for a pathologic F10 gene variant (c.1210T>C, p.Cys404Arg), which impedes correct folding of the catalytic serine protease domain and, therefore, causes a significant reduction in FX levels. The parents, not consanguineous but of the same ethnic community, were found to be heterozygous for this variant and did not have any personal or family history of abnormal bleeding. To the best of our knowledge, this is the first reported case of severe FX deficiency resulting in ICH diagnosed through postmortem genetic analysis. It illustrates the importance of exploring the etiology of fetal or neonatal ICH, which may impact future pregnancies, and the treatment of a potential coagulopathy in the child.

Corrigendum to 'The Hemophilia Joint Health Score version 2.1 Validation in Adult Patients Study: A multicenter international study' [Research and Practice in Thrombosis and Haemostasis, 6/2, (2022) e12690].

[This corrects the article DOI: 10.1002/rth2.12690.].

Reproductive health and hemostatic issues in women and girls with congenital factor VII deficiency: A systematic review.

BACKGROUND: Congenital factor VII (FVII) deficiency is an inherited bleeding disorder, with heterogenous bleeding symptoms. Women with FVII deficiency face hemostatic challenges during menstruation, ovulation, and childbirth. This systematic review evaluated prevalence and management of bleeding symptoms associated with gynecological and obstetric issues in women with FVII deficiency. METHODS: Databases (BIOSIS Previews, Current Contents Search, Embase, and MEDLINE) were searched for studies reporting FVII deficiency and gynecological or obstetric issues in women. Articles were screened using Joanna Briggs Institute checklists and relevant data extracted. RESULTS: One hundred fourteen women were identified from 62 publications. Forty-six women had severe deficiency (FVII:C < 5% or <5 IU/dl). Heavy menstrual bleeding (HMB) was the most common bleeding symptom (n = 94; 82%); hospitalization and urgent medical/surgical interventions for acute HMB episodes were required in 16 women (14%). Seven women reported ovarian bleeding (6%); other bleeding symptoms varied. Patient management was inconsistent and included hemostatic and hormonal treatments. Only four women (7%) reporting vaginal bleeding during pregnancy. Postpartum hemorrhage (PPH) occurred following 12/45 deliveries (27%; 5 [42%] requiring blood transfusion) and was not necessarily prevented by prophylaxis (8 women). CONCLUSION: Women with congenital FVII deficiency have an increased risk of HMB, ovarian bleeding, and PPH, impacting quality of life. Recognition of a bleeding disorder as the cause is often delayed. Management of bleeding complications is heterogeneous due to lack of treatment guidelines. Harmonizing severity classification of FVII deficiency may help standardize treatment strategies and development of specific guidelines for these women.

Exploring social complexities of the COVID-19 pandemic on maternal anxiety: A mixed-methods observational cohort study.

INTRODUCTION: The aim of this mixed-methods, small-scale observational cohort study was to examine if anxiety in pregnant women increased during the COVID-19 pandemic and to examine the subsequent impact on birth outcomes and psychological well-being. This research was conducted across two hospital sites in North London, with participation from 194 pregnant women. METHODS: The GAD-7 questionnaire assessed for mild, moderate and high anxiety at one time point during the antenatal period and was repeated 6 weeks postnatally. Women with moderate to high scores on the GAD-7 were invited to participate in semi-structured interviews. The primary outcome measure was assessment of antenatal and postnatal anxiety. Secondary outcome measures assessed if women with moderate/high GAD-7 scores were more likely to develop a mental health condition during pregnancy, or up to 6 weeks postnatally, and if risk of preterm birth (<37 weeks gestation) and instrumental birth or cesarean section increased. RESULTS: Pearson's correlation indicated a positive and significant correlation between the COVID-19 pandemic, and increased self-reported antenatal GAD-7 anxiety scores (r=0.47, n=194, p<0.001). GAD-7 scores were higher during pregnancy compared to the postnatal period [t(193)=4.63; p=0.001; 95% CI: 0.87-2.16]. Logistic regression did not show an increased likelihood of preterm birth [χ²(1, n=184)=0.999; p=0.971] or instrumental/cesarean section birth in women who scored moderately to highly on the antenatal GAD-7 [χ²(1, n=184)=2.73; p=0.165]. Qualitative analysis was carried out within a social constructionist framework and identified the following themes: anxiety, maternity care, social impact, and coping. CONCLUSIONS: Pregnant women self-reported an increase in antenatal anxiety during July 2020 to April 2021 of the COVID-19 pandemic. Moderate to high anxiety scores were not found to increase the likelihood of preterm birth and birth intervention or developing a mental health condition up to 6 weeks postnatally.

The risk of venous thromboembolism in early pregnancy loss: Review of the literature and current guidelines and the need for guidance - Communication from the SSC on Women's Health Issues for thrombosis and haemostasis.

BACKGROUND: Thromboembolic disease is one of the major causes of mortality and morbidity in pregnancy and the puerperium, with 1 death per 100 000 births attributed to venous thromboembolism (VTE). Factors associated with development of thrombosis are all present in pregnancy, with some of these changes seen from conception. OBJECTIVE: Given how common early pregnancy loss is, the aim of this review is to evaluate the uncertainty surrounding the risk of VTE following early pregnancy loss and termination of pregnancy. METHODS: A structured literature search was conducted to identify existing evidence as well as international pregnancy-specific guidelines regarding assessment and prevention of VTE risk in pregnant women. This review was reviewed, critiqued, and approved by all members of the International Society on Thrombosis and Haemostasis subcommittee for Women's Health Issues in Thrombosis and Haemostasis. RESULTS: Four published original research studies, one clinical comment paper, and six guidelines were reviewed. Despite clear evidence of the increased risk of VTE in pregnancy, there is a lack of guidance regarding evaluation and management after early pregnancy loss. CONCLUSION: International collaborative research to determine the risk of VTE and its prevention in women undergoing surgical termination of pregnancy or following surgical management of early pregnancy loss is urgently needed. Pregnancy-specific risk assessment taking into account preexisting risk factors is advocated. Education of health care professionals involved in early pregnancy care and guidance on management, albeit based on limited existing evidence, are necessary to highlight the need for individualized care.

Platelet storage pool disorder in pregnancy: Utilising thromboelastography to guide a risk-based delivery plan.

We present a case of a 33-year-old woman in her third pregnancy diagnosed with platelet storage pool disorder who had previously suffered two postpartum major obstetric haemorrhages. Platelet storage pool disorder is a rare bleeding disorder where the platelet count is normal but platelet function is impaired due to deficiency of dense granules. A peripartum plan devised by an extensive multi-disciplinary team using principles for managing other bleeding and platelet function disorders helped minimise her risk of major haemorrhage. We also describe how point-of-care thromboelastography can help guide management and enable an individualised risk-benefit discussion with the woman about her anaesthetic choices.

Examining international practices in the management of pregnant women with von Willebrand disease.

BACKGROUND: The management of pregnant women with von Willebrand disease (VWD) is complex as physiological pregnancy-induced increases in plasma von Willebrand factor (VWF) may be blunted or absent. Women with VWD experience a heightened risk of postpartum hemorrhage (PPH) and special consideration must be given regarding neuraxial anesthesia (NA) and the need for prophylaxis at time of delivery. These challenges are compounded by a lack of robust evidence to guide clinical decision-making. OBJECTIVES AND METHODS: To determine the current international clinical practices in the management of pregnancy for women with VWD, the International Society on Thrombosis and Haemostasis (ISTH) conducted an international survey of health-care providers (HCP). RESULTS: One hundred thirty-two respondents from 39 countries were included in the final analysis. Variations in clinical practice were identified in antenatal (monitoring of plasma VWF and ferritin levels), peripartum (optimal plasma VWF target at delivery) and postpartum management (definitions used for PPH and postpartum monitoring). A key area of divergence was suitability for NA for women with type 2 and type 3 VWD, with many respondents advising against the use of NA even with VWF supplementation (29% type 2 VWD, 37% type 3 VWD) but others advising use once plasma VWF activity was >50 IU/dL (57% type 2 VWD; 50% type 3 VWD). CONCLUSIONS: This survey highlighted areas of uncertainty surrounding common management issues for pregnant women with VWD. These data underscore the need for international collaborative research efforts focused on peripartum management to improve care for pregnant women with VWD.

Diagnosis and management of severe congenital protein C deficiency (SCPCD): Communication from the SSC of the ISTH.

Severe congenital protein C deficiency (SCPCD) is rare and there is currently substantial variation in the management of this condition. A joint project by three Scientific and Standardization Committees of the ISTH: Plasma Coagulation Inhibitors, Pediatric/Neonatal Thrombosis and Hemostasis, and Women's Health Issues in Thrombosis and Hemostasis, was developed to review the current evidence and help guide on diagnosis and management of SCPCD. We provide a summary of the clinical presentations, differential diagnoses, appropriate investigations to confirm the diagnosis, approaches for management of the acute situation, and options for long-term management including subsequent pregnancies. We finally provide a set of recommendations to help in this regard.

Gynecologic and obstetric management of women with von Willebrand disease: summary of 3 systematic reviews of the literature.

von Willebrand disease (VWD) disproportionately affects women because of the potential for heavy menstrual bleeding (HMB), delivery complications, and postpartum hemorrhage (PPH). To systematically synthesize the evidence regarding first-line management of HMB, treatment of women requiring or desiring neuraxial analgesia, and management of PPH. We searched Medline and EMBASE through October 2019 for randomized trials, comparative observational studies, and case series comparing the effects of desmopressin, hormonal therapy, and tranexamic acid (TxA) on HMB; comparing different von Willebrand factor (VWF) levels in women with VWD who were undergoing labor and receiving neuraxial anesthesia; and measuring the effects of TxA on PPH. We conducted duplicate study selection, data abstraction, and appraisal of risk of bias. Whenever possible, we conducted meta-analyses. We assessed the quality of the evidence using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. We included 1 randomized trial, 3 comparative observational studies, and 10 case series. Moderate-certainty evidence showed that desmopressin resulted in a smaller reduction of menstrual blood loss (difference in mean change from baseline, 41.6 [95% confidence interval, 16.6-63.6] points in a pictorial blood assessment chart score) as compared with TxA. There was very-low-certainty evidence about how first-line treatments compare against each other, the effects of different VWF levels in women receiving neuraxial anesthesia, and the effects of postpartum administration of TxA. Most of the evidence relevant to the gynecologic and obstetric management of women with VWD addressed by most guidelines is very low quality. Future studies that address research priorities will be key when updating such guidelines.