Distribution of von Willebrand factor levels in young women with and without bleeding symptoms. Influence of ABO blood group and promoter haplotypes

Stefan Lethagen; Andreas Hillarp; Caroline Ekholm; Eva Mattson; Christer Halldén; Britt Friberg

doi:10.1160/TH07-06-0419

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2008; 99(06): 1013-1018
DOI: 10.1160/TH07-06-0419

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Distribution of von Willebrand factor levels in young women with and without bleeding symptoms. Influence of ABO blood group and promoter haplotypes

Authors

Stefan Lethagen

¹Department for Coagulation Disorders, Malmö University Hospital, Sweden

²Center for Hemostasis and Thrombosis, Copenhagen University Hospital (Rigshospitalet), Denmark
Andreas Hillarp

³Department of Clinical Chemistry, Malmö University Hospital, Malmö, Sweden
Caroline Ekholm

²Center for Hemostasis and Thrombosis, Copenhagen University Hospital (Rigshospitalet), Denmark
Eva Mattson

²Center for Hemostasis and Thrombosis, Copenhagen University Hospital (Rigshospitalet), Denmark
Christer Halldén

³Department of Clinical Chemistry, Malmö University Hospital, Malmö, Sweden
Britt Friberg

⁴Department of Obstetrics and Gynecology, Lund University Hospital, Lund, Sweden

Abstract

Summary

The normal distribution of von Willebrand factor (VWF) levels is wide. Low levels are associated with bleeding symptoms and von Willebrand disease (VWD). We have recently described a high prevalence of bleeding symptoms in a whole age group of young females (n = 1,019) from Malmo, Sweden. It was the objective of the present study to evaluate the distribution of VWF levels in young females with or without bleeding symptoms in this population, and the influence of ABO blood group and promoter haplotypes on VWF levels and to identify a possible increased prevalence of VWD in females with bleeding symptoms. A random selection of the female age group (n = 246), into a study group (n = 176) with, and a control group (n = 70) without bleeding symptoms, was evaluated. Eighteen girls had VWF:RCo below the reference range, of which 17 belonged to the study group (17/176, 9.7%), and one to the control group (1/70, 1.4%) (p = 0.017). Blood group O was found in 14/18 girls with low VWF:RCo. There was a highly significant correlation between VWF:RCo and blood group O and non-O genotypes. Two common VWF promoter haplotypes did not contribute to the VWF:RCo variation. VWF levels did not correlate with time during menstrual cycle, or the use of oral contraceptives. No case fulfilled the diagnostic criteria for VWD. In conclusion, low VWF:RCo was significantly more frequent in females with bleeding symptoms. However, we found no case fulfilling strict diagnostic criteria for VWD. The ABO blood group was a strong modifier, but VWF promoter haplotypes had no association to VWF levels in this population.

Keywords

Inherited coagulation disorders - oral contraceptives - von Willebrand - disease - clinical studies - menorrhagia

Volltext

Referenzen

References
1 Friberg B, Orno AK, Lindgren A. et al. Bleeding disorders among young women: a population-based prevalence study. Acta Obstet Gynecol Scand 2006; 85: 200-206.
2 Sadler JE. Von Willebrand disease type 1: a diagnosis in search of a disease. Blood 2003; 101: 2089-2093.
3 Orstavik KH, Magnus P, Reisner H. et al. Factor VIII and factor IX in a twin population. Evidence for a major effect of ABO locus on factor VIII level. Am J Hum Genet 1985; 37: 89-101.
4 Gill JC, Endres-Brooks J, Bauer PJ. et al. The effect of ABO blood group on the diagnosis of von Willebrand disease. Blood 1987; 69: 1691-1695.
5 Keightley AM, Lam YM, Brady JN. et al. Variation at the von Willebrand factor (vWF) gene locus is associated with plasma vWF:Ag levels: identification of three novel single nucleotide polymorphisms in the vWF gene promoter. Blood 1999; 93: 4277-4283.
6 Di Bitondo R, Cameron CL, Daly ME. et al. The –1185 A/G and –1051 G/A dimorphisms in the von Willebrand factor gene promoter and risk of myocardial infarction. Br J Haematol 2001; 115: 701-706.
7 Rodeghiero F, Castaman G, Dini E. Epidemiological investigation of the prevalence of von Willebrand's disease. Blood 1987; 69: 454-459.
8 Werner EJ, Broxson EH, Tucker EL. et al. Prevalence of von Willebrand disease in children: a multiethnic study. J Pediatr 1993; 123: 893-898.
9 Shinmyozu K, Okadome T, Maruyama Y. et al. A study on the frequency of von Willebrand factor deficiency state. Rinsho Ketsueki 1991; 32: 67-68.
10 Cabrera ME, Artigas CG, Paez E. et al. Von Willebrand's disease in the IX Region of Chile. Rev Med Chil 1989; 117: 423-430.
11 Shankar M, Lee CA, Sabin CA. et al. von Willebrand disease in women with menorrhagia: a systematic review. Br J Obstet Gynecol 2004; 111: 734-740.
12 Strandberg K, Lethagen S, Andersson K. et al. Evaluation of a rapid automated assay for analysis of von Willebrand ristocetin cofactor activity. Clin Appl Thromb Hemost 2006; 12: 61-67.
13 Sadler JE, Rodeghiero F. Provisional criteria for the diagnosis of VWD type 1. J Thromb Haemost 2005; 3: 775-777.
14 Sadler JE, Budde U, Eikenboom JC. et al. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost 2006; 4: 2103-2114.
15 Miller CH, Graham JB, Goldin LR. et al. Genetics of classic von Willebrand's disease. I. Phenotypic variation within families. Blood 1979; 54: 117-136.
16 Favaloro EJ, Soltani S, McDonald J. et al. Reassessment of ABO blood group, sex, and age on laboratory parameters used to diagnose von Willebrand disorder: potential influence on the diagnosis vs the potential association with risk of thrombosis. Am J Clin Pathol 2005; 124: 910-917.
17 Kouides PA. Aspects of the laboratory identification of von Willebrand disease in women. Semin Thromb Hemost 2006; 32: 480-484.
18 Eikenboom J, Van Marion V, Putter H. et al. Linkage analysis in families diagnosed with type 1 von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 VWD. J Thromb Haemost 2006; 4: 774-782.
19 Tosetto A, Rodeghiero F, Castaman G. et al. A quantitative analysis of bleeding symptoms in type 1 von Willebrand disease: results from a multicenter European study (MCMDM-1 VWD). J Thromb Haemost 2006; 4: 766-773.