Elevated von Willebrand factor levels during heavy menstrual bleeding episodes limit the diagnostic utility for von Willebrand disease

Abstract

Background Heavy menstrual bleeding (HMB) is often the first bleeding symptom for female individuals with inherited bleeding disorders. Guidelines recommend performing the hemostatic evaluation at HMB presentation. Von Willebrand factor (VWF) levels increase with stress, making it unclear if VWF studies during acute bleeding are beneficial in diagnosing von Willebrand disease (VWD). Objectives To determine the utility of testing for VWD during acute HMB. Patients/Methods This retrospective cohort study evaluated VWF levels of individuals presenting to the emergency department (ED) with HMB from January 1, 2017, to December 31, 2018, after prospective implementation of a clinical practice guideline recommending hemostatic evaluation in the ED. We compared VWF and factor VIII (FVIII) levels between acute presentation and follow‐up visit after bleeding resolution. We compared the diagnostic accuracy of initial and follow‐up labs. Results During the study period, 221 individuals were seen in the ED for acute HMB, and 39 had VWD testing at both time points. Median FVIII and VWF levels were higher during acute bleeding than at follow‐up. The difference in VWF levels between visits was negligible when initial FVIII value was normal. Overall incidence of VWD was 7.5%; 69% of those with VWD had low VWF levels during acute HMB. Conclusion VWD testing during acute HMB detects the majority of individuals with VWD but also leads to elevated levels of VWF, potentially limiting at the accuracy of diagnostic labs during acute bleeding episodes. Delayed testing until resolution of anemia and active bleeding may provide more accurate diagnostic evaluation for VWD.

Health issues in women and girls affected by haemophilia with a focus on nomenclature, heavy menstrual bleeding, and musculoskeletal issues

“…As mentioned above, both one‐stage and chromogenic FVIII levels should be measured when Haemophilia A is suspected. Testing for a coagulopathy in the setting of HMB can be complicated by elevations of VWF in the setting of HMB, as well as delayed platelet aggregation in the setting of anaemia (haemoglobin <10 g/dl) 38,39 . As such, repeat testing may be needed outside of the acute setting.…”

Diagnostic pitfalls and conundrums in type 1 von Willebrand disease

“…While plasma VWF:Ag or VWF:RCo >100 IU/dL has a neg a tive pre dic tive value >95% for VWD, 19 some patients ulti mately diag nosed with VWD may have ini tial test results within the nor mal range (>50 IU/dL). 19,20 In ado les cents with acute HMB, if plasma FVIII:C was not ele vated, only a min i mal change in VWF:Ag and VWF:RCo lev els was observed at retesting (2% and 1%, respec tively), suggesting FVIII:C lev els may help deter mine the need to retest. 20 In a small study of 22 irondefi cient women, retest ing fol low ing iron sup ple men ta tion iden ti fied type 1 VWD in 27% despite nor mal plasma VWF lev els on ini tial test ing.…”

“…19,20 In ado les cents with acute HMB, if plasma FVIII:C was not ele vated, only a min i mal change in VWF:Ag and VWF:RCo lev els was observed at retesting (2% and 1%, respec tively), suggesting FVIII:C lev els may help deter mine the need to retest. 20 In a small study of 22 irondefi cient women, retest ing fol low ing iron sup ple men ta tion iden ti fied type 1 VWD in 27% despite nor mal plasma VWF lev els on ini tial test ing. 21 Due to the known fluc tu a tions in plasma VWF, diag no sis in peo ple with bor der line plasma VWF lev els is more chal leng ing, often resulting in repeated plasma VWF test ing.…”

Diagnosis of Bleeding Disorders in Adolescents Hospitalized for Heavy Menstrual Bleeding

“…Emerging data suggest that iron deficiency may obscure a diagnosis of VWD due to elevations in VWF. 24 Brown and colleagues recently published a retrospective cohort study evaluating VWF antigen levels during acute bleeding and then repeating testing with resolution of bleeding, which demonstrated that factor VIII and VWF are elevated due to HMB. In total, 70% of patients diagnosed with VWD met diagnostic criteria with their inpatient laboratories and VWF levels >100% had high negative predictive value.…”