A decreased and less sustained desmopressin response in hemophilia A carriers contributes to bleeding

Candy, Victoria; Whitworth, Hilary; Grabell, Julie; Thibeault, Lisa; Harpell, Lori; Bowman, Mackenzie; Good, David; Hopman, Wilma M.; Sidonio, Robert F.; James, Paula D.

doi:10.1182/bloodadvances.2018023713

Cited by 17 publications

(22 citation statements)

References 34 publications

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“…In accordance, a recent study in hemophilia carriers showed that participants with an abnormal bleeding score had a lower FVIII response to desmopressin compared with participants with a normal bleeding score. 16 Our current study and the previous analysis in hemophilia carriers show the important, underrated, role of hemostatic response to hemostatic challenges in patients with bleeding disorders. Individuals with comparable baseline hemostatic markers may have a different bleeding phenotype due to a difference in hemostatic response.…”

Section: Discussionsupporting

confidence: 57%

“…In hemophilia carriers, it was also found that FVIII levels 2 hours after desmopressin administration were associated with the bleeding phenotype, whereas there was no association with levels 1 and 4 hours after desmopressin administration. 16 Overall, these results may indicate that a sustained hemostatic response after hemostatic challenge is important to prevent bleeding or to decrease bleeding severity in patients with VWD.…”

Section: Vwf:agmentioning

confidence: 83%

“…The response to hemostatic challenges can be investigated by evaluating VWF and FVIII levels after exposure to desmopressin. 16 Desmopressin stimulates the release of endogenous VWF from Weibel-Palade bodies of the endothelial cells into the circulation, and thus represents an individual's potential to release endogenous VWF into the blood during hemostatic challenges. 1 It is therefore assumed that patients who increase well in VWF and FVIII levels after desmopressin administration may also increase well in VWF and FVIII levels during hemostatic challenges.…”

Section: Introductionmentioning

confidence: 99%

“…1 It is therefore assumed that patients who increase well in VWF and FVIII levels after desmopressin administration may also increase well in VWF and FVIII levels during hemostatic challenges. 16 It was recently shown in a study of hemophilia A carriers that individuals with abnormal bleeding scores had a lower FVIII response to desmopressin compared with those with normal bleeding scores. 16 To the best of our knowledge, no studies have yet been conducted to investigate whether VWF and FVIII levels after desmopressin administration explain the variability in bleeding phenotype of patients with type 1 VWD.…”

Section: Introductionmentioning

confidence: 99%

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von Willebrand factor and factor VIII levels after desmopressin are associated with bleeding phenotype in type 1 VWD

et al. 2019

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Key Points• VWF and FVIII levels after desmopressin, which mimic hemostatic response, are associated with the bleeding phenotype of type 1 VWD patients.• Variability in VWF and FVIII response to hemostatic challenges may partly explain heterogeneity in bleeding phenotype of VWD patients.The bleeding phenotype of patients with type 1 von Willebrand disease (VWD) is very heterogeneous. We hypothesized that this heterogeneity may partly be explained by variability in response of von Willebrand factor (VWF) and factor VIII (FVIII) levels to stress during hemostatic challenges. We therefore investigated whether VWF and FVIII levels after administration of desmopressin, which mimic in vivo hemostatic response during hemostatic challenges, explain the heterogeneity in bleeding phenotype of patients with type 1 VWD. We performed a retrospective cohort study in 122 patients with type 1 VWD. All patients received a test dose of desmopressin shortly after diagnosis. Patients' mean age was 47 6 14 years, and the mean Tosetto bleeding score was 10 6 7. Higher FVIII activity during the complete time course after desmopressin administration (1, 3, and 5-6 hours), and higher VWF and FVIII levels combined at 3 hours after desmopressin administration, were associated with a lower bleeding score: b 5 -0.9 (-1.7; 20.1) and b 5 -1.2 (-1.9; 20.5), respectively, adjusted for age, sex, body mass index (BMI), and comorbidities. Patients with FVIII activity in the highest quartile 3 hours after desmopressin administration had a much lower bleeding score compared with patients in the other 3 quartiles (b 5 -5.1 [-8.2; 22.0]) and also had a lower chance of an abnormal bleeding score (odds ratio 5 0.2 [0.1-0.5]), both adjusted for age, sex, BMI, and comorbidities. In conclusion, VWF and FVIII levels after desmopressin administration, which mimic hemostatic response to hemostatic challenges, are associated with the bleeding phenotype of patients with type 1 VWD. This may partly explain the variability in bleeding phenotype of these patients.

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Section: Discussionsupporting

confidence: 57%

Section: Vwf:agmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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von Willebrand factor and factor VIII levels after desmopressin are associated with bleeding phenotype in type 1 VWD

et al. 2019

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“…These results compare favourably with the few data published on the response to DDAVP and its use in WGHA, 17,18 even if a recent study suggested a decreased and less sustained desmopressin response in WGHA. 19 This study has some limitations, namely the retrospective nature of data collection and the relatively small number of patients.…”

Section: Discussionmentioning

confidence: 97%

Can we compare haemophilia carriers with clotting factor deficiency to male patients with mild haemophilia?

et al. 2019

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Introduction Certain haemophilia carriers demonstrate an increased bleeding tendency, mainly related to clotting factor deficiency. No study has so far formally compared the bleeding phenotype of women and girls with mild FVIII or FIX deficiency and associated management with that of male patients affected by mild haemophilia A and B. Material and methods We retrospectively evaluated 44 women and girls with mild FVIII or FIX deficiency (FVIII or FIX 0.05‐0.5 IU/mL) and 77 male patients with mild haemophilia A or B and compared them with respect to clotting factor level, age at and trigger for diagnosis, as well as treatment modalities. Results After excluding gender‐related haemorrhagic symptoms, haemophilia carriers with plasma factor levels in the mild haemophilia range and male patients affected by mild haemophilia present a comparable haemorrhagic profile, mainly characterized by mucocutaneous and postinjury bleeding. Haemophilia carriers with clotting factor deficiency, however, distinguish themselves in terms of later age at diagnosis, higher mean factor levels and trigger for diagnosis. Conclusions Women and girls with mild FVIII or FIX deficiency should be considered as mild haemophilia patients and have access to care and management inspired from male haemophilia patients while integrating differences and specificities. Larger international studies comparing the clinical presentation and treatment modalities of mild clotting FVIII and FIX deficiencies in both haemophilia males and females should be encouraged.

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Hemophilia Carriers

Wheeler¹,

Sidonio²

2020

Hematology in the Adolescent Female

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A decreased and less sustained desmopressin response in hemophilia A carriers contributes to bleeding

Cited by 17 publications

References 34 publications

von Willebrand factor and factor VIII levels after desmopressin are associated with bleeding phenotype in type 1 VWD

von Willebrand factor and factor VIII levels after desmopressin are associated with bleeding phenotype in type 1 VWD

Can we compare haemophilia carriers with clotting factor deficiency to male patients with mild haemophilia?

Hemophilia Carriers

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