Feasibility of the Von Willebrand disease PREVENT trial

Margaret V. Ragni, Nicoletta Machin, Andra H. James, Craig D. Seaman, Lynn M. Malec, Craig M. Kessler, Barbara A. Konkle, Peter A. Kouides, Anne T. Neff, Claire Philipp, Maria M. Brooks

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Abstract

Background Despite treatment, women with von Willebrand disease (VWD) have lower von Willebrand factor (VWF) levels and greater blood loss at delivery than controls. Current weight-based dosing does not account for the ~ 1.5-fold increase in blood volume in pregnancy. Methods To evaluate the feasibility of a trial to prevent postpartum hemorrhage (PPH), we reviewed pre-pregnancy and 8th month VWF levels in women with VWD with and without PPH following vaginal delivery, assessed VWF concentrate use at delivery by U.S. hemophilia treatment center physician survey, and reviewed thrombosis risk with VWF concentrate by literature review. We determined trial interest and acceptability by structured interviews of physicians and patients. Analysis was by Student's t-test for continuous data, and chi-square or Fisher's exact test for discrete data. Results PPH was associated with lower pre-pregnancy VWF:RCo, p < 0.005; higher pre-pregnancy, 8th and 9th-month weight, each p < 0.001; a family bleeding history, p = 0.036; and VWF concentrate treatment, p = 0.005. Surveyed physicians reported first-line therapy at delivery was VWF concentrate, at a mean dose 50 IU/kg. A trial of a 1.5-fold volume-based dose increase was acceptable to physicians and patients, if it is safe and if costs and visits are minimized. A literature review determined thrombosis risk with VWF concentrate is low, 0.4%. Conclusions This study suggests pre-pregnancy VWF:RCo may predict PPH, but 50–80 IU/kg VWF concentrate dosing may not prevent PPH. If pharmacokinetic modeling confirms volume-based dosing achieves VWF levels comparable to pregnant controls, it may be possible to determine if volume-modified VWF concentrate dosing will reduce PPH in VWD.

Original languageEnglish (US)
Pages (from-to)8-13
Number of pages6
JournalThrombosis research
Volume156
DOIs
StatePublished - Aug 1 2017

Fingerprint

von Willebrand Diseases
von Willebrand Factor
Postpartum Hemorrhage
Pregnancy
Physicians
Thrombosis
Weights and Measures
Hemophilia A
Therapeutics
Blood Volume
Pharmacokinetics

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Ragni, M. V., Machin, N., James, A. H., Seaman, C. D., Malec, L. M., Kessler, C. M., ... Brooks, M. M. (2017). Feasibility of the Von Willebrand disease PREVENT trial. Thrombosis research, 156, 8-13. https://doi.org/10.1016/j.thromres.2017.05.022
Ragni, Margaret V. ; Machin, Nicoletta ; James, Andra H. ; Seaman, Craig D. ; Malec, Lynn M. ; Kessler, Craig M. ; Konkle, Barbara A. ; Kouides, Peter A. ; Neff, Anne T. ; Philipp, Claire ; Brooks, Maria M. / Feasibility of the Von Willebrand disease PREVENT trial. In: Thrombosis research. 2017 ; Vol. 156. pp. 8-13.
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abstract = "Background Despite treatment, women with von Willebrand disease (VWD) have lower von Willebrand factor (VWF) levels and greater blood loss at delivery than controls. Current weight-based dosing does not account for the ~ 1.5-fold increase in blood volume in pregnancy. Methods To evaluate the feasibility of a trial to prevent postpartum hemorrhage (PPH), we reviewed pre-pregnancy and 8th month VWF levels in women with VWD with and without PPH following vaginal delivery, assessed VWF concentrate use at delivery by U.S. hemophilia treatment center physician survey, and reviewed thrombosis risk with VWF concentrate by literature review. We determined trial interest and acceptability by structured interviews of physicians and patients. Analysis was by Student's t-test for continuous data, and chi-square or Fisher's exact test for discrete data. Results PPH was associated with lower pre-pregnancy VWF:RCo, p < 0.005; higher pre-pregnancy, 8th and 9th-month weight, each p < 0.001; a family bleeding history, p = 0.036; and VWF concentrate treatment, p = 0.005. Surveyed physicians reported first-line therapy at delivery was VWF concentrate, at a mean dose 50 IU/kg. A trial of a 1.5-fold volume-based dose increase was acceptable to physicians and patients, if it is safe and if costs and visits are minimized. A literature review determined thrombosis risk with VWF concentrate is low, 0.4{\%}. Conclusions This study suggests pre-pregnancy VWF:RCo may predict PPH, but 50–80 IU/kg VWF concentrate dosing may not prevent PPH. If pharmacokinetic modeling confirms volume-based dosing achieves VWF levels comparable to pregnant controls, it may be possible to determine if volume-modified VWF concentrate dosing will reduce PPH in VWD.",
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Ragni, MV, Machin, N, James, AH, Seaman, CD, Malec, LM, Kessler, CM, Konkle, BA, Kouides, PA, Neff, AT, Philipp, C & Brooks, MM 2017, 'Feasibility of the Von Willebrand disease PREVENT trial', Thrombosis research, vol. 156, pp. 8-13. https://doi.org/10.1016/j.thromres.2017.05.022

Feasibility of the Von Willebrand disease PREVENT trial. / Ragni, Margaret V.; Machin, Nicoletta; James, Andra H.; Seaman, Craig D.; Malec, Lynn M.; Kessler, Craig M.; Konkle, Barbara A.; Kouides, Peter A.; Neff, Anne T.; Philipp, Claire; Brooks, Maria M.

In: Thrombosis research, Vol. 156, 01.08.2017, p. 8-13.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Feasibility of the Von Willebrand disease PREVENT trial

AU - Ragni, Margaret V.

AU - Machin, Nicoletta

AU - James, Andra H.

AU - Seaman, Craig D.

AU - Malec, Lynn M.

AU - Kessler, Craig M.

AU - Konkle, Barbara A.

AU - Kouides, Peter A.

AU - Neff, Anne T.

AU - Philipp, Claire

AU - Brooks, Maria M.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Background Despite treatment, women with von Willebrand disease (VWD) have lower von Willebrand factor (VWF) levels and greater blood loss at delivery than controls. Current weight-based dosing does not account for the ~ 1.5-fold increase in blood volume in pregnancy. Methods To evaluate the feasibility of a trial to prevent postpartum hemorrhage (PPH), we reviewed pre-pregnancy and 8th month VWF levels in women with VWD with and without PPH following vaginal delivery, assessed VWF concentrate use at delivery by U.S. hemophilia treatment center physician survey, and reviewed thrombosis risk with VWF concentrate by literature review. We determined trial interest and acceptability by structured interviews of physicians and patients. Analysis was by Student's t-test for continuous data, and chi-square or Fisher's exact test for discrete data. Results PPH was associated with lower pre-pregnancy VWF:RCo, p < 0.005; higher pre-pregnancy, 8th and 9th-month weight, each p < 0.001; a family bleeding history, p = 0.036; and VWF concentrate treatment, p = 0.005. Surveyed physicians reported first-line therapy at delivery was VWF concentrate, at a mean dose 50 IU/kg. A trial of a 1.5-fold volume-based dose increase was acceptable to physicians and patients, if it is safe and if costs and visits are minimized. A literature review determined thrombosis risk with VWF concentrate is low, 0.4%. Conclusions This study suggests pre-pregnancy VWF:RCo may predict PPH, but 50–80 IU/kg VWF concentrate dosing may not prevent PPH. If pharmacokinetic modeling confirms volume-based dosing achieves VWF levels comparable to pregnant controls, it may be possible to determine if volume-modified VWF concentrate dosing will reduce PPH in VWD.

AB - Background Despite treatment, women with von Willebrand disease (VWD) have lower von Willebrand factor (VWF) levels and greater blood loss at delivery than controls. Current weight-based dosing does not account for the ~ 1.5-fold increase in blood volume in pregnancy. Methods To evaluate the feasibility of a trial to prevent postpartum hemorrhage (PPH), we reviewed pre-pregnancy and 8th month VWF levels in women with VWD with and without PPH following vaginal delivery, assessed VWF concentrate use at delivery by U.S. hemophilia treatment center physician survey, and reviewed thrombosis risk with VWF concentrate by literature review. We determined trial interest and acceptability by structured interviews of physicians and patients. Analysis was by Student's t-test for continuous data, and chi-square or Fisher's exact test for discrete data. Results PPH was associated with lower pre-pregnancy VWF:RCo, p < 0.005; higher pre-pregnancy, 8th and 9th-month weight, each p < 0.001; a family bleeding history, p = 0.036; and VWF concentrate treatment, p = 0.005. Surveyed physicians reported first-line therapy at delivery was VWF concentrate, at a mean dose 50 IU/kg. A trial of a 1.5-fold volume-based dose increase was acceptable to physicians and patients, if it is safe and if costs and visits are minimized. A literature review determined thrombosis risk with VWF concentrate is low, 0.4%. Conclusions This study suggests pre-pregnancy VWF:RCo may predict PPH, but 50–80 IU/kg VWF concentrate dosing may not prevent PPH. If pharmacokinetic modeling confirms volume-based dosing achieves VWF levels comparable to pregnant controls, it may be possible to determine if volume-modified VWF concentrate dosing will reduce PPH in VWD.

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Ragni MV, Machin N, James AH, Seaman CD, Malec LM, Kessler CM et al. Feasibility of the Von Willebrand disease PREVENT trial. Thrombosis research. 2017 Aug 1;156:8-13. https://doi.org/10.1016/j.thromres.2017.05.022