Population differences in von Willebrand factor levels affect the diagnosis of von Willebrand disease in African‐American women

Miller, Connie H.; Dilley, Anne; Richardson, Lisa C.; Hooper, W. Craig; Evatt, Bruce L.

doi:10.1002/ajh.1090

Cited by 80 publications

(82 citation statements)

References 24 publications

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“…FVIII levels in nonhemophilic populations are thought to span a greater than 5-fold range [21], with age [22,23], smoking [23], ABO blood group [24], and heritability [24,25] as strong correlates of levels. Additionally, previous population studies have demonstrated that plasma FVIII:C levels are influenced by ethnicity, with higher levels in African Americans [21,23,26]. Moreover, FVIII varies with VWF to keep its ratio relatively constant over a wide range of VWF levels [21]; however, the increase in FVIII:C levels were not in parallel with VWF levels in our cohort.…”

Section: Discussioncontrasting

confidence: 64%

Hypercoagulability in adolescent girls on oral contraceptives‐global coagulation profile and estrogen receptor polymorphisms

Zia

Callaghan

et al. 2015

American J Hematol

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Oral contraceptive (OCP) induced changes on coagulation are complex with high inter-individual variability. The precise reason for differences in this variability is unknown. We hypothesized that global coagulation assays better delineate these changes and variability in hypercoagulability may be the result of differences in estrogen metabolism and thrombophilia. Fifty-two adolescents initiating OCPs were prospectively enrolled; 33 subjects completed the study. Samples were analyzed prior to and after OCPs for procoagulant and anticoagulant factor activities and thrombin generation (TG) 1/-thrombomodulin. Participants were genotyped for common thrombophilia and estrogen receptor-a (ESR-a) single nucleotide polymorphisms (SNPs). SNP genotypes were compared to coagulation parameters; TG parameters and differences pre and post OCPs were examined. At baseline, a striking finding was elevated FVIII levels. FVL was absent in all and F2 G20210A was present in one participant. The ESR-a polymorphism was present in heterozygous state in 59% and homozygous state in 21% participants. There were no differences in VWF levels and FVIII: C after being on OCPs. Protein S levels decreased with OCPs. Sixty percent of participants showed evidence of hypercoagulability on TG testing on OCPs. Higher thrombin peak and endogenous thrombin potential (ETP) were seen on TG after OCPs. With thrombomodulin, ETP and thrombin peak did not decrease after OCPs, signifying 'thrombomodulin resistance'. We demonstrated that OCPs induce a state of "variable" hypercoagulability in adolescents, predominantly through the protein S pathway. Genetic and nongenetic factors may account for the variable increase in hypercoagulability. Further research is needed to understand this.

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Section: Discussioncontrasting

confidence: 64%

Hypercoagulability in adolescent girls on oral contraceptives‐global coagulation profile and estrogen receptor polymorphisms

Zia

Callaghan

et al. 2015

American J Hematol

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“…The difference was statistically significant only in the larger study, which identified vWD in 6.6% of women with menorrhagia, compared to 0.8% of controls (odds ratio 8.6) [14]. In a separate analysis by race, vWD was significantly more frequent in white than African American women with menorrhagia (15.9% vs. 1.4%, respectively) [14,17]. The reason for the racial difference is unclear because population screening suggests a similar prevalence of vWD among different racial groups [1].…”

Section: Frequency Of Vwd In Women With Menorrhagiamentioning

confidence: 71%

“…The reason for the racial difference is unclear because population screening suggests a similar prevalence of vWD among different racial groups [1]. The observation that African Americans have significantly higher vWF levels than whites could account for a lower frequency of the disorder [17,18]. However, the racial difference in prevalence persisted when a raceadjusted reference range was used for diagnosis [17].…”

Section: Frequency Of Vwd In Women With Menorrhagiamentioning

confidence: 99%

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von Willebrand's disease and menorrhagia: Prevalence, diagnosis, and management

Kujovich¹

2005

American J Hematol

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The reported prevalence of von Willebrand's disease (vWD) is increased in women with menorrhagia, with current estimates ranging from 5% to 20%. The consistent results of multiple studies suggest testing should be included in the evaluation of patients with menorrhagia, especially in unexplained cases and prior to surgical intervention. Although a cyclic variation in von Willebrand's factor levels has not been confirmed, several studies suggest lower levels during menses and the early follicular phase. Menorrhagia is one of the most common bleeding manifestations of von Willebrand's disease, reported by 60-95% of women afflicted with this bleeding disorder. Menorrhagia is typically severe, often resulting in anemia and interfering with quality of life. Despite the frequency of menorrhagia, there is no consensus on optimal management. Although oral contraceptives are frequently prescribed, there are no studies confirming their efficacy using objective measures of response. Desmopressin was associated with an 80-92% response rate in several uncontrolled studies relying on patient assessment of efficacy. However, a small, randomized trial found no significant reduction in menstrual blood flow compared with placebo. There are anecdotal reports of the successful use of antifibrinolytic agents alone and in combination with other therapies. There are no studies comparing the relative efficacy and safety of the available medical therapies for von Willebrand's disease associated menorrhagia. Until these studies are completed, treatment should be individualized based on von Willebrand's disease subtype, patient age, contraceptive needs, and personal preference. Am.

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“…Plasma VWF vary relative to ABO blood group and race (Coppola et al, 2003;Miller et al, 2003;Sukhu et al, 2003;Haley et al, 2002;O'Donnell and Laffan, 2001;Miller et al, 2001;Nitu-Whalley et al, 2000;Shima et al, 1995;Caekebeke-Peerlinck et al, 1989). Also, ABO blood group influences the rate of proteolysis of VWF by ADAMTS-13 (Bowen, 2003) and show relationship between thrombotic and coronary risk factor (Schleef et al, 2005;Ray et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Plasma von Willebrand factor level and its associated parameters: Reference ranges in Nigeria

Ezigbo¹,

Ukaejiofo²,

Chinyeaka³

2015

J. Med. Lab. Diagn.

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Population differences in von Willebrand factor levels affect the diagnosis of von Willebrand disease in African‐American women

Abstract: Diagnosis of von Willebrand disease (vWD) is based on a panel of laboratory tests that

Cited by 80 publications

References 24 publications

Hypercoagulability in adolescent girls on oral contraceptives‐global coagulation profile and estrogen receptor polymorphisms

Hypercoagulability in adolescent girls on oral contraceptives‐global coagulation profile and estrogen receptor polymorphisms

von Willebrand's disease and menorrhagia: Prevalence, diagnosis, and management

Plasma von Willebrand factor level and its associated parameters: Reference ranges in Nigeria

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