Treatment of patients with severe von Willebrand disease undergoing elective surgery by administration of recombinant VWF
The present invention relates to method for pretreating a subject with severe von Willebrand disease prior to a surgical procedure comprising administering to the subject a dose ranging from about 20 IU/kg to about 60 IU/kg rVWF between about 12 hours and about 24 hours prior to the surgical procedure, and wherein Factor VIII is not administered with the rVWF prior to the surgical procedure.
1 . A method for pre-treatment of a subject with severe von Willebrand disease (VWD) prior to a surgical procedure, wherein said pre-treatment comprises the following steps:
(i) administering 40-60 IU/kg of recombinant Von Willebrand Factor (rVWF) to said subject between 12 hours and 24 hours prior to said surgical procedure, wherein Factor VIII (FVIII) is not administered with the rVWF prior to the surgical procedure, wherein the rVWF comprises ultra-large multimers (ULMs), wherein the ULMs comprise over 40 subunits and are at least 10,000 kDa;
(ii) measuring the subject's FVIII: C level within 3 hours prior to said procedure; and
(iii) administering 5-90 IU/kg rVWF to said subject within 1 hour prior to said surgical procedure.
2 . The method of claim 1 , wherein FVIII is not administered after said surgical procedure.
3 . The method of claim 1 , wherein said surgical procedure is selected from the group consisting of major surgery, minor surgery, and oral surgery.
4 . The method of claim 1 , wherein said subject is administered 50-60 IU/kg rVWF between 12 hours and 24 hours prior to said surgical procedure and said surgical procedure is a minor surgical procedure.
5 . The method of claim 1 , wherein said subject is administered 45-60 IU/kg rVWF between 12 hours and 24 hours prior to said surgical procedure and said surgical procedure is a major surgical procedure.
6 . The method of claim 1 , wherein said subject is administered 5-50 IU/kg rVWF 1 hour prior to the surgical procedure and said surgical procedure is a minor surgical procedure.
7 . The method of claim 1 , wherein said subject is administered 15-90 IU/kg rVWF 1 hour prior to said surgical procedure and said surgical procedure is a major surgical procedure.
8 . The method of claim 1 , wherein said subject is administered 20-50 IU/kg rVWF 1 hour prior to said surgical procedure and said surgical procedure is an oral surgical procedure.
9 . The method of claim 1 , wherein said subject is administered 10-50 IU/kg rVWF during said surgical procedure and said surgical procedure is an oral surgical procedure.
10 . The method of claim 1 , wherein said subject is administered 70-220 IU/kg rVWF after said surgical procedure.
11 . The method of claim 1 , wherein said subject is administered 70-150 IU/kg rVWF after said surgical procedure and said surgical procedure is a minor surgical procedure.
12 . The method of claim 1 , wherein said subject is administered 150-220 IU/kg rVWF after said surgical procedure and said surgical procedure is a major surgical procedure.
13 . The method of claim 1 , wherein said subject is administered 20-50 IU/kg rVWF after said surgical procedure and said surgical procedure is an oral surgical procedure.
14 . The method of claim 1 , wherein said subject is administered a total dosage of 100-220 IU/kg rVWF and said surgical procedure is a minor surgical procedure.
15 . The method of claim 1 , wherein said subject is administered a total dosage of 220-320 IU/kg rVWF and said surgical procedure is a major surgical procedure.
16 . The method of claim 1 , wherein said subject is administered a total dosage of 70-190 IU/kg rVWF and said surgical procedure is an oral surgical procedure.
17 . The method of claim 1 , wherein said surgical procedure is a major surgical procedure and said pre-treatment comprises administering at least two approximately equal doses of rVWF prior to the surgical procedure.
18 . The method of claim 1 , wherein said surgical procedure is a minor surgical procedure and said pre-treatment comprises administering at least two doses of rVWF prior to the surgical procedure, wherein the first dose is larger than the second dose.
19 . The method of claim 1 , wherein said surgical procedure is an oral surgical procedure and said pre-treatment comprises administering at least two approximately equal doses of rVWF prior to the surgical procedure.
20 . The method of claim 1 , wherein said surgical procedure further comprises step (iv) administering recombinant factor VIII immediately after said administration of 5-90 IU/kg of rVWF if the subject's measured FVIII: C level is below 30 IU/dL for a minor/oral surgical procedure or below 60 IU/dL for a major surgical procedure.
21 . The method of claim 1 , wherein the rVWF comprises a percentage of high molecular weight (HMW) rVWF multimers, wherein the HMW rVWF multimers comprise 10%-40% rVWF decamers or higher order multimers.
22 . The method of claim 1 , wherein the FVIII: C level when measured is increased to at least 30 IU/dL, wherein said surgical procedure is a minor surgical procedure.
23 . The method of claim 1 , wherein the FVIII: C level is increased to at least 60 IU/dL, wherein said surgical procedure is a major surgical procedure.
24 . A method for pre-treatment of a subject with severe von Willebrand disease (VWD) prior to surgical procedure, wherein said pre-treatment comprises the following steps:
(i) administering 40-60 IU/kg of recombinant Von Willebrand Factor (rVWF) to said subject between 12 hours and 24 hours prior to said surgical procedure, wherein Factor VIII (FVIII) is not administered with the rVWF prior to the surgical procedure, wherein the rVWF comprises ultra-large multimers (ULMs), wherein the ULMs comprise over 40 subunits and are at least 10,000 kDa;
(ii) measuring the subject's FVIII: C level within 3 hours prior to said procedure; and
(iii) administering 5-90 IU/kg rVWF to said subject within 1 hour prior to said surgical procedure, wherein said surgical procedure is an oral surgical procedure.
25 . The method of claim 24 , wherein the rVWF comprises a percentage of high molecular weight (HMW) rVWF multimers, wherein the HMW rVWF multimers comprise 10%-40% rVWF decamers or higher order multimers.
26 . The method of claim 24 , wherein the FVIII: C level when measured is increased to at least 30 IU/dL, wherein said surgical procedure is a minor surgical procedure.
27 . The method of claim 24 , wherein the FVIII: C level is increased to at least 60 IU/dL, wherein said surgical procedure is a major surgical procedure.