The spectrum and severity of bleeding in adolescents with low von Willebrand factor–associated heavy menstrual bleeding

Srivaths, Lakshmi; Minard, Charles G.; O’Brien, Sarah H.; Wheeler, Allison P.; Mullins, Eric S.; Sharma, Mukta; Sidonio, Robert F.; Jain, Shilpa; Zia, Ayesha; Ragni, Margaret V.; Kulkarni, Roshni; Dietrich, Jennifer E.; Kouides, Peter A.

doi:10.1182/bloodadvances.2020002081

Cited by 17 publications

(48 citation statements)

References 29 publications

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“…Finally, it is clear that there is a subgroup of patients with VWF levels in the 30 to 50 IU/dL who do bleed significantly despite their mild reductions in plasma VWF levels. 19,21,46,47 Importantly, the bleeding tendency in these low VWF patients does not correlate with VWF levels and thus is likely multifactorial in etiology. 16 Individuals with low VWF, particularly those with high BAT scores, certainly require perioperative hemostatic treatment.…”

Section: Interindividual Variability In Bleeding Phenotypementioning

confidence: 92%

“…44,45 Interestingly, several recent independent studies have demonstrated that some individuals with mild reductions in plasma VWF levels do have significantly increased bleeding assessment tool (BAT) scores. 19,21,46,47 In particular, some women with VWF in the 30 to 50 IU/dL range have subjective and objective evidence of abnormal heavy menstrual bleeding and postpartum hemorrhage (PPH). 46,47 In these patients, bleeding severity is not correlated with plasma VWF levels and pathological VWF sequence variants are less common.…”

Section: Low Vwfmentioning

confidence: 99%

“…19,21,46,47 In particular, some women with VWF in the 30 to 50 IU/dL range have subjective and objective evidence of abnormal heavy menstrual bleeding and postpartum hemorrhage (PPH). 46,47 In these patients, bleeding severity is not correlated with plasma VWF levels and pathological VWF sequence variants are less common. 19,21 Moreover, linkage studies have shown that bleeding phenotype in these families is actually independent of the VWF locus and consequently inheritance patterns are not necessarily autosomal dominant.…”

Section: Low Vwfmentioning

confidence: 99%

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Toward Personalized Treatment for Patients with Low von Willebrand Factor and Quantitative von Willebrand Disease

O’Donnell

2021

Semin Thromb Hemost

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The biological mechanisms involved in the pathogenesis of type 2 and type 3 von Willebrand disease (VWD) have been studied extensively. In contrast, although accounting for the majority of VWD cases, the pathobiology underlying partial quantitative VWD has remained somewhat elusive. However, important insights have been attained following several recent cohort studies that have investigated mechanisms in patients with type 1 VWD and low von Willebrand factor (VWF), respectively. These studies have demonstrated that reduced plasma VWF levels may result from either (1) decreased VWF biosynthesis and/or secretion in endothelial cells and (2) pathological increased VWF clearance. In addition, it has become clear that some patients with only mild to moderate reductions in plasma VWF levels in the 30 to 50 IU/dL range may have significant bleeding phenotypes. Importantly in these low VWF patients, bleeding risk fails to correlate with plasma VWF levels and inheritance is typically independent of the VWF gene. Although plasma VWF levels may increase to > 50 IU/dL with progressive aging or pregnancy in these subjects, emerging data suggest that this apparent normalization in VWF levels does not necessarily equate to a complete correction in bleeding phenotype in patients with partial quantitative VWD. In this review, these recent advances in our understanding of quantitative VWD pathogenesis are discussed. Furthermore, the translational implications of these emerging findings are considered, particularly with respect to designing personalized treatment plans for VWD patients undergoing elective procedures.

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Section: Interindividual Variability In Bleeding Phenotypementioning

confidence: 92%

Section: Low Vwfmentioning

confidence: 99%

Section: Low Vwfmentioning

confidence: 99%

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Toward Personalized Treatment for Patients with Low von Willebrand Factor and Quantitative von Willebrand Disease

O’Donnell

2021

Semin Thromb Hemost

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“…[5][6][7][8][9][10] Importantly, from a clinical perspective, these studies have demonstrated that a significant number of patients with plasma VWF:Ag in the 30-50 IU/dl range have a bleeding phenotype. [5][6][7][10][11][12] In particular, significantly increased heavy menstrual bleeding and postpartum hemorrhage have been reported in some women with low VWF. 5,10 Despite its prevalence and associated morbidity, the biological mechanisms responsible for the reduced plasma VWF:Ag in patients with low VWF remain unclear.…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7][10][11][12] In particular, significantly increased heavy menstrual bleeding and postpartum hemorrhage have been reported in some women with low VWF. 5,10 Despite its prevalence and associated morbidity, the biological mechanisms responsible for the reduced plasma VWF:Ag in patients with low VWF remain unclear. 4 However, they have been shown to be inherited independent of the VWF gene on chromosome 12 in some families.…”

Section: Introductionmentioning

confidence: 99%

Management of elective procedures in low von Willebrand factor patients in the LoVIC study

Doherty

Lavin

O’Sullivan

et al. 2021

Journal of Thrombosis and Haemostasis

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Background Most individuals with mild to moderate reductions in plasma von Willebrand factor (VWF) levels do not demonstrate increased bleeding. However, some patients with plasma VWF levels of 30–50 IU/dl do have a significant bleeding phenotype. Management of these “low VWF” patients, who may have significant bleeding scores >10, around times of elective procedures continues to pose a common clinical challenge because of a lack of evidence. Objective To investigate the safety and efficacy of different periprocedural management options for adult patients with low VWF. Methods Treatment and outcomes were retrospectively reviewed for 160 invasive procedures performed in 60 patients with well characterized low VWF enrolled in the previously described Low Von Willebrand factor Ireland Cohort study. Results We demonstrate that 1‐desamino‐8‐D‐arginine vasopressin is efficacious in preventing bleeding for both minor or major elective procedures in adult low VWF patients, even in those with significant bleeding histories. In addition, tranexamic acid alone is effective for low VWF patients undergoing nondental minor procedures. Importantly, age‐related increases in plasma VWF:antigen levels above 50 IU/dl were not necessarily associated with complete correction of bleeding phenotype. Procedure‐related bleeding complications were increased in low VWF patients who did not receive any hemostatic cover before their procedure. Conclusion Elective procedures in adult patients with low VWF should be managed in liaison with a comprehensive care tertiary referral center so that personalized treatment plans may be implemented before all minor or major elective procedures.

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Low von Willebrand Factor in Children and Adolescents

Srivaths

Kouides

2021

JAMA Pediatr

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on Willebrand disease (VWD) is the most common inherited bleeding disorder, with a reported prevalence in the general population of 0.1% to 1%, 1,2 occurring in all races and ethnicities. 3 The disease is named after the Finnish internist who discovered the disorder in 1926 as a familial hemorrhagic diathesis in a 5-year-old girl from the Aland Islands, who died 10 years later of menorrhagia. 4 von Willebrand disease is classified as a quantitative or qualitative deficiency of von Willebrand factor (VWF). The quantitative deficiency includes the common partial or type 1 VWD (VWF level <30 IU/dL) and the rare severe or type 3 VWD (VWF <5 IU/dL). The qualitative deficiency, namely, type 2 VWD, is caused by structural abnormalities of the von Willebrand protein. Normal VWF levels range from 50 to 200 IU/dL, and levels that range from 30 to 50 IU/dL are considered low VWF. Whether low VWF should be considered a risk factor for bleeding or a bleeding disorder has been a decade-long debate. 5 Some studies [6][7][8] have documented increased bleeding symptoms in patients with low VWF, highlighting the clinical significance of this entity, and other studies 9-11 have provided insights into the pathogenesis of low VWF. Children and ado-lescents with VWF deficiencies often present to primary care physicians (PCPs) with symptoms such as easy bruising, mucosal bleeding, heavy menstrual bleeding (HMB), and posttraumatic and postsurgical bleeding during operations, such as tonsillectomy and adenoidectomy. 12,13 In adolescent girls with HMB in particular, the quality-of-life impact can be substantial. Consequently, it is important for physicians to be aware of this condition for early detection, appropriate specialty referrals, and continued comanagement of these patients. This narrative review of low VWF in children and adolescents clarifies the differences between type 1 VWD and low VWF; summarizes the recent findings about the clinical spectrum, pathogenesis, diagnostic evaluation, and management of the disorder; and emphasizes the role PCPs play in the care of these patients. Low VWFThe diagnosis of low VWF is made in patients with a bleeding phenotype, with VWF levels ranging from 30 to 50 IU/dL. Previous IMPORTANCE Recent studies have documented increased bleeding symptoms and related complications in patients with low von Willebrand factor (VWF), highlighting the clinical significance of this entity. Because children and adolescents with VWF deficiencies often present to primary care physicians with bleeding symptoms, physicians need to be aware of this condition for early detection.OBSERVATIONS Studies have found that children and adolescents with low VWF (VWF levels of 30-50 IU/dL) can present with clinically significant bleeding, including mucosal, menstrual, postsurgical, and posttraumatic bleeding, leading to complications such as anemia, iron deficiency, transfusion, hospitalization, and poor quality of life. Detecting and promptly managing low VWF in children and adolescents with bleeding are essential because fai...

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The spectrum and severity of bleeding in adolescents with low von Willebrand factor–associated heavy menstrual bleeding

Cited by 17 publications

References 29 publications

Toward Personalized Treatment for Patients with Low von Willebrand Factor and Quantitative von Willebrand Disease

Toward Personalized Treatment for Patients with Low von Willebrand Factor and Quantitative von Willebrand Disease

Management of elective procedures in low von Willebrand factor patients in the LoVIC study

Low von Willebrand Factor in Children and Adolescents

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